NCCN Non Hodgkins Lymphoma Treatment Guidelines.pdf by shensengvf

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									Non-Hodgkin’s
Lymphoma
Treatment Guidelines for Patients




Version II/ December 2004
       Non-Hodgkin’s
       Lymphoma
       Treatment Guidelines for Patients
      Version II/ December 2004




The goal of the National Comprehensive Cancer Network (NCCN) and the
American Cancer Society (ACS) partnership is to provide patients and the
general public with state-of-the-art cancer treatment information in an easy to
understand language. This information, based on the NCCN’s Clinical Practice
Guidelines, is meant to assist you in a discussion with your doctor. It is not
intended to replace the expertise and judgment of your doctor.
NCCN Clinical Practice Guidelines, the professional versions, were developed by
a diverse panel of experts. The guidelines are a statement of consensus of its
authors regarding the scientific evidence and their views of currently accepted
approaches to treatment. These guidelines are updated as new significant data
become available. The Patient Information version will be updated accordingly
and will be available on-line through the NCCN and the American Cancer
Society Web sites. To ensure you have the most recent version, you may contact
the American Cancer Society at 1-800-ACS-2345 or the NCCN at 1-888-909-NCCN.

©2005 by the American Cancer Society (ACS) and the National Comprehensive
Cancer Network. All rights reserved. The information herein may not be reprinted
in any form for commercial purposes without the expressed written permission
of the ACS. Single copies of each page may be reproduced for personal and non-
commercial uses by the reader.
                                                     Contents

Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .5
Making Decisions About Non-Hodgkin’s Lymphoma Treatment . . . . . . . . . . . . . . .5
What Is Non-Hodgkin’s Lymphoma? . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .6
Types of Non-Hodgkin’s Lymphoma . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .8
How Is Non-Hodgkin’s Lymphoma Diagnosed? . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .11
Non-Hodgkin’s Lymphoma Stages . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .15
Types of Treatment for Non-Hodgkin’s Lymphoma . . . . . . . . . . . . . . . . . . . . . . . . . . .16
Other Things to Consider During and After Treatment . . . . . . . . . . . . . . . . . . . . . .22
Clinical Trials . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .23
Treatment Guidelines . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .25
Decision Trees
     Chronic Lymphocytic Leukemia (CLL)/Small Lymphocytic
     Lymphoma (SLL) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .26
     Follicular Lymphoma (Small or Mixed Cell) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .32
     Gastric MALT Lymphoma . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .40
     Nongastric MALT Lymphoma/Marginal Zone Lymphoma . . . . . . . . . . . . . . . .46
     Mantle Cell Lymphoma . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .48
     Diffuse Large B-Cell Lymphoma . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .52
     Burkitt’s Lymphoma . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .62
     Lymphoblastic Lymphoma . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .66
     AIDS-Related B-Cell Lymphoma . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .70
Glossary . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .75
                          Member Institutions

Arthur G. James Cancer Hospital and Richard J. Solove
Research Institute at The Ohio State University
City of Hope Cancer Center
Dana-Farber/Partners CancerCare
Duke Comprehensive Cancer Center
Fox Chase Cancer Center
Fred Hutchinson Cancer Research Center/
Seattle Cancer Care Alliance
H. Lee Moffitt Cancer Center & Research Institute
at the University of South Florida
Huntsman Cancer Institute at the University of Utah
The Sidney Kimmel Comprehensive Cancer Center
at Johns Hopkins
Memorial Sloan-Kettering Cancer Center
Robert H. Lurie Comprehensive Cancer Center
of Northwestern University
Roswell Park Cancer Institute
St. Jude Children’s Research Hospital/University
of Tennessee Cancer Institute
Stanford Hospital and Clinics
UCSF Comprehensive Cancer Center
University of Alabama at Birmingham Comprehensive
Cancer Center
University of Michigan Comprehensive Cancer Center
The University of Texas M. D. Anderson Cancer Center
UNMC/Eppley Cancer Center at the Nebraska Medical Center
Introduction                                          • What are the risks or side effects
                                                        associated with each treatment and
With this booklet, patients have access to              how will they affect my quality of life?
information on the way non-Hodgkin’s                  • What can I do to prepare myself for
lymphoma is treated at the nation’s leading             treatment, reduce side effects, and
cancer centers. Originally developed for                hasten my recovery?
cancer specialists by the National                    • When will I be able to return to my
Comprehensive Cancer Network (NCCN),                    normal activities?
these treatment guidelines have now been
translated for the public by the American
Cancer Society (ACS).                              Making Decisions About
   Since 1995, doctors have looked to the          Non-Hodgkin’s Lymphoma
NCCN for guidance on the highest quality,          Treatment
most effective advice on treating cancer. For
more than 85 years, the public has relied on       In the United States, about 54,370 people
the American Cancer Society for information        (28,850 men and 25,520 women) will be diag-
about cancer. The Society’s books and              nosed with non-Hodgkin’s lymphoma this
brochures provide reliable cancer informa-         year. These figures include both adults and
tion to hundreds of thousands of patients,         children. It is the fifth most common cancer
their families, and friends. This collaboration    in the United States, excluding nonmelanoma
between the NCCN and ACS provides an               skin cancers.
authoritative and understandable source of             Although some types of non-Hodgkin’s
cancer treatment information for the public.       lymphoma are among the most common
   These patient guidelines will help you better   childhood cancers, over 95% of non-
understand your cancer treatment and your          Hodgkin’s lymphoma cases occur in adults.
doctor’s advice. We urge you to discuss them       The average age at diagnosis is in the 60s. The
with your doctor. To make the best possible        risk of developing most types of non-
use of this information, you might ask your        Hodgkin’s lymphoma increases throughout
doctor the following questions:                    life, and the elderly have the highest risk.
   • What type of non-Hodgkin’s lymphoma               Although non-Hodgkin’s lymphoma is a
      do I have?                                   serious disease, it can be treated and, in some
   • What stage is it?                             cases, cured. Care should be provided by a
   • Is it a fast growing lymphoma?                team of health care professionals who are
   • How do the stage and type of lymphoma         experienced in treating non-Hodgkin’s lym-
      affect my outlook for cure?                  phoma. This team may include a surgeon,
   • What are my treatment options?                medical oncologist, radiation oncologist,




                                                                                                     5
    pathologist, oncology nurse, radiologist, and     organ). Most of the time they are found in
    social worker often along with your primary       bean shaped organs called lymph nodes.
    care doctor.                                          Other types of cancer can develop in other
       This information is written to help you        organs and then spread to lymphoid tissue.
    understand your options for treatment of          But these cancers are not lymphomas. For
    non-Hodgkin’s lymphoma so that you and            example, cancer that develops in the lungs
    your cancer care team can work together to        and then spreads to the lymph nodes is still
    decide which treatment best meet your needs.      called lung cancer. Lymphomas start from
       On the following pages you’ll find flow-       lymphocytes in either lymph nodes or other
    charts that doctors call ”decision trees.” The    sites of lymphoid tissue such as the bone
    charts represent the most common types of         marrow and can spread from there.
    non-Hodgkin’s lymphoma, and each one                  There are 2 main types of lymphomas.
    shows how you and your doctor can arrive at       Hodgkin’s lymphoma (or Hodgkin’s disease) is
    the choices you need to make about your           named after Dr. Thomas Hodgkin, who first
    treatment. There are other types of non-          described it. All other types of lymphoma are
    Hodgkin’s lymphoma. They are discussed            called non-Hodgkin’s lymphoma. The non-
    along with treatment on the ACS Website at        Hodgkin’s lymphomas are very different from
    www.cancer.org.                                   Hodgkin’s disease in how they develop and
       To reach an informed decision, you will        spread and in how they are treated. The
    need to understand some of the medical            information here refers only to the different
    terms that your doctors use. You will find        types of non-Hodgkin’s lymphoma. Each type
    information on what is non-Hodgkin’s lym-         varies in how it is treated and how it
    phoma, the different types of non-Hodgkin’s       responds to treatment.
    lymphoma, how lymphoma is diagnosed,
    staging, and treatment. We’ve also provided a     Lymphoid Tissue
    glossary of medical terms.                        The main cell type found in lymphoid tissue
                                                      is the lymphocyte. The 2 main types of
                                                      lymphocytes are B lymphocytes (or B cells)
    What Is Non-Hodgkin’s                             and T lymphocytes (or T cells). Although both
    Lymphoma?                                         types can develop into lymphomas, B-cell
                                                      lymphomas are more common. B-cell lym-
    Non-Hodgkin’s lymphoma is cancer that             phomas account for 85% of cases of non-
    starts in lymphoid tissue (also called lym-       Hodgkin’s lymphoma; T-cell lymphomas make
    phatic tissue). Lymphoid tissue is the main       up the other 15%.
    part of the immune system. It is formed by           Normal T cells and B cells do different
    several different types of cells that work        jobs within the immune system. B cells help
    together to fight infections. These cells also    protect the body against bacteria by produc-
    react to foreign tissue (such as a transplanted   ing immunoglobulins (also called antibodies).


6
The antibodies attach to certain substances              Lymph nodes increase in size when they
on the surface of bacteria and attract certain       fight an infection. Lymph nodes that grow in
immune system cells that kill the antibody-          reaction to infection are called reactive nodes
coated bacteria.                                     (or hyperplastic nodes) and are often tender
    T cells help protect the body against viruses,   to the touch. An enlarged lymph node is not
fungi, and some bacteria. They recognize             usually serious. People with sore throats or
specific substances found in virus-infected          colds often have enlarged lymph nodes in the
cells and destroy these cells. T cells can also      neck. But a large lymph node is also the most
release substances called cytokines that attract     common sign of lymphoma.
certain other types of white blood cells, which          The spleen is found under the lower part
then digest the infected cells. T cells are also     of the rib cage, on the left side of the body. An
thought to destroy some types of cancer cells,       average adult spleen weighs about 5 ounces.
as well as the cells of transplanted organs.         The spleen contains lymphocytes and other
Some types of T cells play a role in helping or      immune system cells to help fight infection.
blocking the work of other immune system             It stores healthy blood cells and filters out
cells.                                               damaged blood cells, bacteria, and cell waste.
    There are several types of T cells, each             The thymus gland is located in the front of
with a special job, and there are also several       the chest at the base of the neck. While a fetus
stages of B-cell and T-cell development. Each        is growing in the mother’s uterus, the thymus
type of lymphoma tends to look like one of           plays a vital role in producing T lymphocytes.
the normal lymphocytes at a certain level of         The thymus gland’s size (about 1 ounce) and
development.                                         activity peak between 1 and 20 years of age.
    This information is helpful because know-        Although its size and role decline with age,
ing the type of lymphoma a person has is the         the thymus continues to function throughout
first step in considering treatment options. So,     life as part of the immune system.
learning about lymphocytes is the first step in          Adenoids and tonsils are collections of
understanding lymphomas, their diagnosis,            lymphoid tissue located at the back of the
and their treatment.                                 throat. They produce antibodies against germs
                                                     that are breathed in or swallowed. They are
Organs That Contain                                  easy to see when they become enlarged dur-
Lymphoid Tissue                                      ing an infection or if they become cancerous.
Lymph nodes are small, bean-shaped organs            The stomach and intestinal tract also contain
found throughout the body and connected by           lymphatic tissue.
a system of lymphatic vessels. These vessels are         The bone marrow (the soft inner part of
like veins, except that instead of carrying blood,   bones) produces red blood cells, blood
they carry lymph (a clear fluid containing           platelets, and white blood cells, including
waste products and excess fluid from tissues).       lymphocytes. Red blood cells carry oxygen
They also carry immune system cells traveling        from the lungs to the rest of the body.
to lymph nodes from other tissues.                   Platelets plug up small holes in blood vessels

                                                                                                         7
    caused by cuts or scrapes. The main job of        Table 1. Lymphoma Types
    white blood cells is fighting infections. In      (based on how they grow)
    addition to lymphocytes, the other main type      Slow-growing             • Chronic Lymphocytic
                                                                                 Leukemia/Small Lymphocytic
    of white blood cells is the neutrophil (also
                                                                                 Lymphoma
    known as granulocytes, or “polys”).                                        • Follicular Lymphoma
                                                                               • MALT Lymphoma

                                                      Aggressive               • Diffuse Large B Cell
    Types of Non-Hodgkin’s                                                       Lymphoma
                                                                               • Mantle Cell Lymphoma*
    Lymphoma
                                                      Highly Aggressive • Burkitt’s Lymphoma
    Because there are so many types of non-                             • Lymphoblastic Lymphoma
    Hodgkin’s lymphoma, several different systems                       • AIDS-Related Lymphoma

    have been developed to classify this disease.     * Although mantle cell lymphoma is not very fast growing, it
                                                      responds poorly to standard treatment
    Most doctors now use the REAL/WHO classi-
    fication (Revised European-American
    Lymphoma/World Health Organization). The          B-Cell Lymphomas
    REAL/WHO system sorts the types of lym-           Chronic lymphocytic leukemia/small
    phoma by the appearance of the lymphoma           lymphocytic lymphoma: Although one
    cells, presence of proteins on the surface of     disease is a leukemia and one is a lymphoma,
    the cells, and genetic features. Although         these two diseases are related and account
    there are many kinds of lymphomas, only the       for 7% of all lymphomas. In both kinds, the
    most common types are discussed below.            same type of cell, the small lymphocyte, is
        To simplify discussion of non-Hodgkin’s       involved. The only difference is in where the
    lymphomas, the many specific types are some-      cancer occurs. It is mostly in the blood in
    times grouped together into slow growing (or      leukemia, and it is mainly in the lymph nodes
    indolent), aggressive, or highly aggressive       in lymphoma. Both are slow-growing
    categories (see Table 1). Aggressive and highly   diseases although leukemia, which is much
    aggressive lymphomas grow more rapidly            more common, tends to be slower. They are
    and spread through the body quickly.              not considered curable with standard treat-
    Without treatment, most patients live only a      ments. But depending on the stage and
    short time. Fortunately, most aggressive and      growth rate of the disease, patients can live
    highly aggressive lymphomas respond well to       well over 10 years with this lymphoma.
    chemotherapy, and many can be cured.                 Recently it has become clear that there
                                                      are 2 kinds of chronic lymphocytic leukemia.
                                                      One is very slow growing and rarely needs
                                                      treatment. The other kind grows faster and
                                                      almost always needs to be treated. Doctors
                                                      can tell them apart by testing for a substance


8
called ZAP-70 in the leukemia cells. This is a          Mantle cell lymphoma: About 6% of
new test that is not available everywhere.          lymphomas are this type. When diagnosed, it
Cells that contain this substance are usually       is usually widespread and will involve lymph
the faster growing kind. Sometimes, these           nodes, bone marrow, and, very often, the spleen.
slow-growing lymphomas can change (trans-           Men are most often affected; the average age
form) over time into a more aggressive type         of patients is in the early 60s. Although this is
of lymphoma.                                        not a very fast growing lymphoma, it is a
    Follicular lymphoma: About 22% of all           serious one. Only 20% of patients survive at
lymphomas are follicular lymphomas. These           least 5 years.
cells tend to grow in a nodular pattern similar         Diffuse large B-cell lymphoma: This
to the normal patterns in lymph nodes. This         kind makes up 31% of all lymphomas. It is a
is a slow growing lymphoma. It mostly arises        fast-growing lymphoma. The usual symptoms
in many lymph node sites in the body, as well       are a rapidly growing mass in the body or in a
as in the bone marrow. The average age for          lymph node that can be felt. About one-third
people with this lymphoma is 60. It is rare in      of these lymphomas are confined to one part
very young people. In advanced stages it is not     of the body (localized). Although this lymphoma
considered curable by standard treatment.           usually starts in lymph nodes, it can grow in
The percentage of patients who live at least 5      other areas such as the intestines, bone, and
years after their cancer is diagnosed is about      the brain or spinal cord. When it is localized
60% to 70%. In time, many follicular lym-           this type of lymphoma is considered to be
phomas transform into a fast growing diffuse        more curable than when it has spread to
large B-cell lymphoma.                              other parts of the body. It can affect any age
    Extranodal marginal zone B-cell lym-            group but mostly occurs in older people. The
phomas - mucosa-associated lymphoid                 average age of patients is the mid-60s. About
tissue (MALT) lymphomas: This type makes            40% to 50% of people with this lymphoma are
up 8% of lymphomas. Most MALT lymphomas             cured with treatment.
start in the stomach. They are thought to stem          Burkitt’s lymphoma: This type makes up
from an infection by bacteria called Helicobacter   about 2% of all lymphomas. It is named after
pylori. This lymphoma can also develop in other     the doctor who first described this disease in
sites like lung, skin, thyroid, salivary gland,     African children and young adults. Another
small or large intestine, breast, and tissues       kind of lymphoma called Burkitt’s-like lym-
surrounding the eye. In those cases, the cancer     phoma looks like Burkitt’s lymphoma but the
is called nongastric MALT lymphoma. Usually         cells are slightly larger. Because they are hard
MALT lymphomas are confined to the area             to tell apart, the REAL/WHO classification
where they began and are not widespread.            combines them. In the African type, it often
The average age for patients with this lym-         starts as tumors of the jaws or other facial
phoma is 60. It is a slow-growing lymphoma          bones. In the more common types seen in the
and often can be put into prolonged remission       United States, the lymphoma usually starts in
and possibly cured in its early stages.             the abdomen, where it forms a large tumor

                                                                                                        9
     mass. It can also spread to the brain and spinal   T-Cell Lymphomas
     fluid. The average age of patients is about 30,    Anaplastic large T/null-cell lymphoma:
     and close to 90% of patients are male.             About 2% of lymphomas are this kind. The
     Although this is a fast-growing lymphoma,          cells are large. It is more common in young
     about half of patients are cured by aggressive     people. It usually starts in lymph nodes and
     chemotherapy.                                      can also spread to skin. There is one form
         AIDS-related B-cell lymphoma: The              that begins in the skin. Although this type of
     major types of non-Hodgkin’s lymphoma seen         lymphoma appears to be fast growing, treat-
     in people with AIDS are diffuse large B-cell       ment with chemotherapy or radiotherapy is
     lymphoma, Burkitt’s lymphoma, and primary          often successful, especially if the tumor cells
     central nervous system lymphoma. The first         contain a protein called ALK-1. Many patients
     two are discussed above. The main difference       with this lymphoma are cured. It is generally
     in treating these lymphomas in people with         treated like a diffuse large B-cell lymphoma.
     AIDS is that often their outcome depends on            Peripheral T-cell lymphomas: There are
     how well the AIDS is responding to treatment.      several kinds of peripheral T-cell lymphomas,
     Also, these patients are very sensitive to the     which, in total, account for about 7% of all
     side effects of chemotherapy, especially the       lymphomas. They are mostly treated like dif-
     effect on blood counts. This is becoming less      fuse large B-cell lymphomas. There are a variety
     of a problem because of advances in treating       of rare subtypes of these lymphomas which
     the HIV infection that causes AIDS. Also, the      include:
     number of people developing these lym-                 • Histology unspecified: Extranodal
     phomas has decreased in the last few years               natural killer/T-cell lymphoma, nasal
     because of the improved HIV treatment.                   type which often involves the upper
         Primary central nervous system lym-                  airway passages, such as the nose and
     phoma: This lymphoma usually involves the                nasopharynx, but also invades the skin
     brain (then called primary brain lymphoma),              and gastrointestinal tract.
     but it also can be found in the spinal cord and        • Enteropathy type T-cell lymphoma
     in tissues around the spinal cord and inside             which can occur in people who are
     the eye. In time, it spreads throughout the              sensitive to gluten, the main protein
     central nervous system. In the past, this was            in wheat flour.
     a rare tumor, but it has become more common            • Subcutaneous panniculitis-like T-cell
     with the AIDS epidemic. Most people develop              lymphoma which invades the deepest
     headache and confusion. They can also have               layers of the skin and causes nodules
     vision problems and, rarely, paralysis. The              to form under the skin.
     outlook for people with this condition is
                                                           Lymphoblastic lymphoma/leukemia:
     poor. About 30% of people can live 5 years
                                                        This type can be either B cell or T cell. This
     with modern treatments.
                                                        disease can be considered either a lymphoma
                                                        or leukemia, depending on whether more

10
(leukemia) or less (lymphoma) than 25% of         vein that carries blood from the head and arms
bone marrow cells are lymphoma cells. Usually     back to the heart (called the superior vena
the lymphoma forms in the mediastinum (the        cava) passes near the thymus and lymph nodes
area in front of the heart and behind the         inside the chest. Growth of lymphoma may
chest bone). About 2% of all lymphomas fall       compress this vein. This causes swelling of
into this group. Patients are most often (75%)    the head and arms, known as SVC syndrome,
men, and their average age is 25. The cell is     which can be life threatening. Patients with
small to middle-sized. The lymphoma is fast       SVC syndrome need to be treated as soon as
growing, but if it hasn’t spread to the bone      possible.
marrow when first diagnosed, the chance of            Lymphomas of the stomach often cause
cure with chemotherapy is quite good.             pain in the stomach, nausea, and reduced
                                                  appetite. Primary central nervous system
                                                  lymphomas cause headache, trouble think-
How Is Non-Hodgkin’s                              ing and moving parts of the body, personality
Lymphoma Diagnosed?                               changes, and, sometimes, epileptic seizures.
                                                      In addition to symptoms and signs caused
Signs and Symptoms                                by local effects of cancer growth, non-Hodgkin’s
Non-Hodgkin’s lymphoma may cause many             lymphoma can produce rather vague symp-
different signs and symptoms, depending on        toms, such as unexplained weight loss, fever,
where it develops in the body.                    profuse sweating (enough to soak clothing)
    Non-Hodgkin’s lymphoma can lead to easily     particularly at night, or severe itchiness.
seen or felt lymph nodes close to the surface     Doctors sometimes call these “B symptoms.”
of the body (such as lymph nodes on the sides     The presence of B symptoms is associated
of the neck, in the groin or underarm areas,      with a worse outlook.
or above the collar bone). These enlarged             The diagnosis of lymphoma may be
nodes are usually noticed by the patient, a       delayed or difficult because enlarged lymph
family member, or a health care professional.     nodes are more commonly caused by infections
    When lymphoid tissue in the abdomen is        than by non-Hodgkin’s lymphoma. Doctors
involved, the abdomen can become swollen.         often wait to see if swollen nodes change in
This may be due to large collections of fluid     size without or with antibiotic treatment. If the
or a tumor. When lymphoma causes swelling         node continues to grow, either a small piece
of lymphoid tissue near the intestines, passage   of the node or, more commonly, the entire
of feces through the compressed area may be       node should be removed for examination
blocked. The pressure or blockage can also        under the microscope (biopsy) and by other
cause discomfort or abdominal pain.               laboratory tests. A biopsy may be needed right
    When lymphoma starts in the thymus or         away if the node is hard or large or if its
lymph nodes in the chest, irritation or com-      location or other symptoms strongly suggests
pression of the nearby windpipe (trachea) can     lymphoma is present.
cause coughing or trouble breathing. The large

                                                                                                      11
     Medical History and                                    Fine needle aspiration (FNA) biopsy:
     Physical Examination                               FNA uses a very thin needle and a syringe to
     The first step in making a diagnosis is for        withdraw a small amount of tissue from the
     your doctor to take your medical history,          tumor mass. The doctor can aim the needle
     which includes questions about symptoms            while feeling an enlarged node near the sur-
     and risk factors. The doctor will perform a        face of the body. If the tumor is deep inside the
     thorough physical examination, especially          body, the doctor can guide the needle while
     checking lymph nodes, the adenoid and tonsil       viewing a computed tomography (CT) scan
     areas, the spleen, and other internal organs.      (see discussion of imaging tests later in this
     The doctor will also ask about weight loss,        section). It is especially useful for finding out
     fever, and night sweats, as well other questions   whether there is lymphoma in a lymph node
     about your health.                                 of a patient who already has been diagnosed.
        If signs or symptoms suggest that you               The main advantage of FNA is that it does
     might have non-Hodgkin’s lymphoma, more            not require surgery. The disadvantage is that
     examinations and tests will be done to be          in some cases the thin needle cannot remove
     certain that this disease is present and, if so,   enough tissue for a definite diagnosis of non-
     to determine the exact type of non-Hodgkin’s       Hodgkin’s lymphoma. It is not recommended
     lymphoma.                                          to make the first diagnosis of lymphoma.
                                                        However, advances in performing lab tests
     Biopsies                                           (discussed later in this section) and the grow-
     A biopsy is the only way to diagnose non-          ing experience of many doctors with FNA have
     Hodgkin’s lymphoma. There are several biopsy       improved the accuracy of this procedure.
     procedures, and the doctor’s choice is based       FNA is also very useful in diagnosing other
     on each patient’s unique situation.                cancers that spread to lymph nodes.
         Excisional or incisional biopsy: A surgeon         Bone marrow aspiration and biopsy: In
     cuts through the skin to remove the entire         bone marrow aspiration, a needle and syringe
     node (excisional biopsy) or a small part of a      are used to remove small amounts of bone
     large tumor (incisional biopsy or core needle      marrow. For a bone marrow biopsy, a larger
     biopsy). If the node is near the skin surface,     needle is used to remove a cylinder of bone and
     this is a simple operation that can be done        marrow, about 1⁄16 inch across and 1 inch long.
     with local anesthesia (numbing medicine). But      Both samples are usually taken from marrow
     if the node is inside the chest or abdomen,        at the back of the hip after the area has been
     general anesthesia is used (the patient is         numbed with local anesthesia. These tests can
     asleep). This method almost always provides        be used for the initial diagnosis and for see-
     enough tissue to diagnose the exact type of        ing how far the cancer has spread (staging).
     non-Hodgkin’s lymphoma; it is preferred if it          Lumbar puncture: In some instances
     can be done without too much discomfort for        when involvement of the central nervous sys-
     the patient.                                       tem (brain and spinal cord) is suspected, a


12
thin needle is inserted into the spinal cavity      types of non-Hodgkin’s lymphoma from one
in the lower back (below the level of the           another and from other diseases.
spinal cord) to withdraw some cerebrospinal             Flow cytometry: The cells being examined
fluid, which is examined for lymphoma cells.        by this test are treated with special laboratory
This test is often called a “spinal tap.”           antibodies and passed in front of a laser
                                                    beam. Each antibody sticks only to cells with
Laboratory Tests                                    certain types of molecules on their surface. If
All biopsy specimens are examined under a           the cells contain those molecules, the laser
microscope by a doctor with special training in     will cause them to give off light of a different
recognizing cells from blood and lymphoid tis-      color, which is measured and analyzed by a
sue diseases. The doctor, a pathologist, looks at   computer. This test can help determine
the size and shape of the cells and how the cells   whether lymph node swelling is due to non-
are arranged in the lymph node. Pathologists        Hodgkin’s lymphoma, some other cancer, or
who specialize in diagnosing lymphoma can           some other disease. It has become very useful
often tell best which type of lymphoma a            in helping doctors determine the exact type
patient has. In addition to pathology, special      of non-Hodgkin’s lymphoma so that they can
laboratory tests like immunohistochemistry          choose the right treatment.
and flow cytometry are needed to accurately             Cytogenetics: This technique uses a
diagnose the type of non-Hodgkin’s lymphoma.        microscope to examine cells to see if part of
    To simplify discussion of non-Hodgkin’s         one chromosome is abnormally attached to
lymphomas, the many specific types are              part of a different chromosome (translocation),
sometimes grouped together into low-grade,          as happens in certain types of lymphoma.
intermediate-grade, or high-grade categories.       Normal human cells each contain 46 chro-
High-grade lymphomas grow more rapidly and          mosomes (giant DNA molecules that control
spread through the body quickly. Without            the cells’ growth and metabolism). In addition
treatment, most patients live only a short          to translocations, some lymphoma cells may
time. The term “aggressive” is often used to        have too many chromosomes.
describe intermediate and high-grade                    Molecular genetic studies: Tests of lym-
lymphomas. Most high-grade lymphomas                phoma cell DNA can also detect transloca-
respond well to chemotherapy, and many can          tions that are not visible under a microscope
be cured.                                           in cytogenetic tests. And DNA tests can also
    Immunohistochemistry: In this test, a           find some translocations involving parts of
part of the biopsy sample is treated with special   chromosomes too small to be seen under a
laboratory antibodies. The cells are treated so     microscope. In the future, as we learn more
that certain types of them change color. The        about lymphomas, this may become the
color change can be seen under a microscope.        most useful test for determining what kind of
This test may be helpful in identifying different   lymphoma is present.



                                                                                                       13
     Imaging Tests                                       outline structures in your body. A second set
     Imaging tests are used to find tumors inside        of pictures is then taken.
     the body. These tests are an important part of          A special kind of CT, the spiral CT, uses a
     staging.                                            rapid scanner that diminishes organ move-
         Chest x-ray: An x-ray is done to look for       ment from the patient taking breaths and
     enlarged lymph nodes inside the chest. It can       can provide greater detail.
     also detect fluid and any tumors in the lungs.          CT scans can also be used to precisely
         Ultrasound: Ultrasound uses sound waves         guide a biopsy needle into an enlarged lymph
     and their echoes to produce a picture of internal   node. For this procedure, called a CT-guided
     organs or masses. A small microphone-like           needle biopsy, the patient remains on the CT
     instrument called a transducer emits sound          scanning table while a radiologist advances a
     waves. These high-frequency sound waves             biopsy needle toward the mass. CT scans are
     are transmitted into the area of the body           repeated until the doctors are sure that the
     being studied and echoed back. The sound            needle is within the mass. A fine needle
     wave echoes are picked up by the transducer         biopsy sample (tiny fragment of tissue) or a
     and converted by a computer into an image           core needle biopsy sample (a thin cylinder of
     that is displayed on a computer screen. This        tissue about 1⁄2 inch long and less than 1⁄8 inch
     test uses no radiation, which is why it is often    in diameter) is removed and examined under
     used to look at developing fetuses. To have an      a microscope.
     ultrasound examination, you simply lie on a             Magnetic resonance imaging (MRI):
     table and a technician moves the transducer         MRI scans use radio waves and strong mag-
     over the part of your body being examined.          nets instead of x-rays. The energy from the
     Usually, the skin is first lubricated with oil.     radio waves is absorbed and then released in
     Sometimes an ultrasound can be used to find         a pattern formed by the type of tissue and by
     masses in the abdomen.                              certain diseases. A computer translates the
         Computed tomography (CT): The CT scan           pattern of radio waves given off by the tissues
     is an x-ray procedure that produces detailed        into a very detailed image of parts of the
     cross-sectional images of your body. Instead        body. A contrast material might be injected
     of taking one picture, as does a conventional       just as with CT scans but is used less often.
     x-ray, a CT scanner takes many pictures as it       MRI scans are helpful in examining the brain
     rotates around you. A computer then combines        and spinal cord.
     these pictures into an image of a slice of your         Positron emission tomography (PET):
     body. The machine will create multiple              PET uses glucose (a form of sugar) that con-
     images of the part of your body that is being       tains a radioactive atom. A special camera can
     studied. A CT scan is useful for looking at         detect the radioactivity. Cancer cells absorb
     lymphoma in the abdomen, pelvis, chest, head,       high amounts of the radioactive sugar because
     and neck. Often after the first set of pictures     of their high rate of metabolism. PET is used
     is taken, you will get an intravenous injection     to look for lymphoma throughout your body.
     of a “dye,” or contrast agent, that helps better    A PET scan can be more helpful than several

14
different x-rays because it scans your whole       can be examined under the microscope to
body. It may also tell if an enlarged lymph        determine if cancer is present and what kind
node contains lymphoma or is noncancerous          of cancer it is. For upper endoscopy, the tube
(benign). PET is also used after treatment to      is passed down through the mouth to view
help decide if an enlarged lymph node still        the esophagus, stomach, and first part of the
contains lymphoma or is merely scar tissue.        small bowel.
Although this test is relatively new, it is
becoming widely used to examine people
with lymphomas.                                    Non-Hodgkin’s
    Gallium scan: The radiologist injects          Lymphoma Stages
radioactive gallium into a vein. It is attracted
to areas of lymphoma in the body. A special        Staging is a process of finding out how far a
camera can detect the radioactivity, showing       cancer has spread. Once non-Hodgkin’s lym-
the location of the radioactive gallium. These     phoma is diagnosed, tests are done to deter-
tests can find tumors that might be non-           mine the stage of the disease (extent of spread).
Hodgkin’s lymphoma in bones and other              The treatment and prognosis (outlook) for
organs. The gallium scan will not detect most      a patient with non-Hodgkin’s lymphoma
slow-growing lymphomas but will recognize          depend on the exact type and the stage of the
aggressive lymphomas.                              lymphoma.
    Bone scan: A different radioactive sub-           Tests used to gather information for stag-
stance is used for bone scans. After it is         ing often include:
injected, it travels to areas of the bone that        • physical examination
are damaged. If there is lymphoma in bone, it         • blood tests
often causes bone damage, and a bone scan             • bone marrow aspiration and biopsy
will find it. But a bone scan will also pick up       • a lumbar puncture (spinal tap) (this is
noncancerous problems, such as arthritis and             not always done)
fractures. It is not generally used in the early      • imaging tests, including a chest x-ray,
staging process for non-Hodgkin’s lymphoma.              chest/abdomen/pelvis CT or MRI scan,
                                                         and PET scan and/or gallium scan.
Other tests
                                                      The staging system most often used to
Endoscopy: This procedure uses a very flex-
                                                   describe the spread of non-Hodgkin’s lym-
ible lighted tube with a video camera on the
                                                   phoma in adults is called the Ann Arbor staging
end. The camera is connected to a television
                                                   system. The stages are represented by Roman
set, allowing the doctor to clearly see any
                                                   numerals I through IV. The letter “B” is added
masses in the lining of the digestive organs. If
                                                   (stage IIIB, for example) if B symptoms
something that shouldn’t be there is seen,
                                                   (unexplained weight loss, soaking sweats,
small pieces of tissue can be removed
                                                   high fever,) are present. For patients without
through the endoscope (biopsy). The tissue
                                                   these symptoms, the letter “A” is added to their


                                                                                                       15
     stage. Lymphomas that grow into organs from          For each unfavorable prognostic factor, 1
     lymph nodes have “E” added to their stage        point is assigned. The index divides people
     ( for example, stage IIE).                       with lymphomas into 4 categories. The low
         • Stage I: The lymphoma is in a lymph        category (0 or 1 point) means that the person
            node or nodes in only one region, such    with lymphoma has mostly good factors (is
            as the neck, groin, or underarm.          young, has stage I disease, is able to work, and
         • Stage II: The lymphoma is in two           so on). The highest category (4 or 5 points)
            groups of lymph nodes, and these are      means mostly or all unfavorable factors (high
            on the same side of the diaphragm (the    stage, high LDH, can’t get out of bed, and so
            breathing muscle that aids breathing      on). No matter what the type of lymphoma,
            and separates the chest and abdomen).     more than 75% of people in the lowest group
            For example, this might include nodes     will live longer than 5 years, whereas only 30%
            in the underarm and neck area, but        of people in the highest group live 5 years.
            not the combination of underarm and           The prognostic index lets a doctor plan
            groin nodes.                              treatment better than he or she could from just
         • Stage III: The lymphoma is only in         the pathology report and staging information.
            lymph nodes but on both sides of the      This has become more important as new, more
            diaphragm.                                effective treatments — but sometimes with
         • Stage IV: The lymphoma is widespread       more side effects — have been developed.
            in an organ or organs, skin, or bone      The index tells us whether these treatments
            marrow.                                   are needed.

     International Prognostic Index
     This index was developed to help predict the     Types of Treatment for
     outcome of people with large cell lymphoma.      Non-Hodgkin’s Lymphoma
     The index depends on 5 factors. In the list
     below, the unfavorable prognostic factor is in   In recent years, much progress has been
     bold type.                                       made in treating non-Hodgkin’s lymphoma.
        • age (below or above 60)                         The treatment options depend on the
        • stage (I and II vs. III and IV)             type of lymphoma and its stage, as well as the
        • absence or presence of lymphoma             prognostic index. Of course, no 2 patients are
           outside of lymph nodes                     exactly alike, and standard treatment options
        • performance status (able to function        are often tailored to each patient’s unique
           normally or needing lots of help with      situation.
           daily activities)                              It is important to know and understand
        • serum LDH (a protein found in the blood     all treatment options. It is often a good idea to
           that goes up in the presence of fast-      seek a second opinion. This can give you more
           growing tumors — the index looks for       information and help you feel more confident
           whether the LDH is normal or elevated)     about the treatment plan that is chosen.

16
Surgery                                              Chemotherapy
Surgery is often used to get a tissue sample to      Chemotherapy uses drugs that are injected
diagnose and classify lymphoma, but it is very       into a vein or a muscle or taken by mouth.
rarely used as treatment because lymphoma            These drugs enter the bloodstream and reach
is considered a systemic disease, involving the      all areas of the body, making this treatment
lymphatic system that circulates lymphatic           very useful for lymphoma. Depending on the
fluid throughout the body. However, surgery          type and the stage of the lymphoma, chemo-
is sometimes used to treat lymphomas that            therapy may be used alone or in combination
start in certain extranodal organs, such as          with radiation therapy. In some cases, chemo-
the thyroid or stomach, and have not spread          therapy is given by injection into the spinal
beyond these organs.                                 fluid (intrathecal injection) to kill lymphoma
                                                     cells on the surface of the brain and spinal cord.
Radiation Therapy                                        Many drugs are useful in the treatment of
Radiation therapy uses high-energy rays to           patients with lymphoma. Usually, several drugs
kill cancer cells. Radiation focused on a cancer     are combined. (See Table 2 for examples of
from a source outside the body is called             combination chemotherapy treatments for
external beam radiation. This is the type of         lymphoma.) The treatments all have different
radiation therapy most often used to treat           schedules, but they are usually repeated
non-Hodgkin’s lymphoma. Radiation might              several times in cycles given 3 or 4 weeks
be used as the main (primary) treatment of           apart. Sometimes a patient may take one
early (stage I or II) non-Hodgkin’s lymphomas.       chemotherapy combination for several cycles
More often, it is used along with chemotherapy.      and later switch to a different one if the first
Radiation therapy can also be used to ease           combination does not seem to be working.
(palliate) symptoms caused by lymphoma
when it affects internal organs, such as the         Table 2. Combination Chemotherapy
                                                     Treatments
brain or spinal cord, or causes pain by pressing
                                                     CHOP       cyclophosphamide, doxorubicin,
on nerves.                                                      vincristine, prednisone
    Side effects of radiation therapy may
include mild skin problems or fatigue.               ICE        ifosfamide, carboplatin, etoposide

Radiation of the abdomen may cause upset             DHAP       dexamethasone, cisplatin, cytarabine
stomach and diarrhea. These usually go away
                                                     MIME       mitoguazone, ifosfamide, methotrexate,
after radiation is finished. Chest radiation ther-              etoposide
apy may damage the lungs and lead to trouble
breathing. Side effects of brain radiation therapy
usually become most serious 1 or 2 years after          Chemotherapy drugs kill lymphoma cells,
treatment and may include headaches and              but they can also damage normal cells. For
difficulty thinking. Radiation may also make         this reason, some side effects occur. These
the side effects of chemotherapy worse.              depend on the type of drugs, the amount taken,


                                                                                                          17
     and the length of treatment. Temporary side           may be given before signs of infection appear
     effects might include nausea and vomiting,            but most often are given at the earliest sign of
     loss of appetite, loss of hair, and mouth sores.      an infection, such as fever. If platelet counts
     Because chemotherapy can damage the blood-            are very low, the patient may receive platelet
     producing cells of the bone marrow, patients          transfusions to protect against bleeding.
     may have low blood cell counts. This can              Likewise, fatigue caused by very low red blood
     result in an increased chance of infection            cell counts is treated with red blood cell
     (due to low white blood cells), easy bleeding         transfusions. White blood cell transfusions are
     or bruising after minor cuts or injuries (due         not useful because these cells exist in such
     to low platelet counts), and fatigue (due to          low numbers in the donor blood.
     low red blood cell counts).                               Tumor lysis syndrome is a side effect of
         There are often ways to lessen these side         the rapid breakdown of cells during very
     effects. For example, antinausea drugs can be         effective chemotherapy for some bulky
     given to prevent or reduce nausea and vomit-          (large) lymphomas. When the lymphoma cells
     ing. Drugs known as growth factors (G-CSF or          are destroyed, they release normal cellular
     GM-CSF, for example) are sometimes given to           components in large amounts into the blood-
     keep the white blood cell counts higher and           stream, which may damage, in particular, the
     thus reduce the chance of infection. Another          kidneys and heart. This condition can be pre-
     type of growth factor, erythropoietin, helps          vented by giving extra fluids and certain drugs,
     prevent anemia (too few red blood cells).             such as sodium bicarbonate, allopurinol, or
         If a patient’s white blood cell counts are very   rasburicase, which help the body get rid of
     low, the risk of infection can be reduced by:         these substances.
         • avoiding exposure to people with                    Organs that could be directly damaged by
            known or suspected bacteria, fungi,            chemotherapy drugs include the kidneys,
            or virus infections                            liver, testes, ovaries, brain, heart, and lungs.
         • paying special attention to washing             Some effects occur during and shortly after
            hands                                          treatment while others may not occur until
         • wearing a surgical mask or having               much later. While being treated, patients are
            visitors wear a mask, a gown, and              watched closely so serious side effects are
            surgical gloves                                avoided. If serious side effects occur, the
         • not eating fresh, uncooked fruit and            chemotherapy may have to be reduced or
            other foods that might carry germs             stopped, at least for a short time. Careful
         • avoiding contact with children because          monitoring and adjustment of drug doses are
            they are more likely than adults to            important to avoid long-term side effects to
            carry infections                               organs. One of the most serious late compli-
                                                           cations of successful chemotherapy is the
        Another way to protect patients with low
                                                           possibility of developing leukemia. This affects
     white blood cell counts against infection is
                                                           a small percentage of lymphoma patients.
     treatment with powerful antibiotics. These


18
   Patients who are to receive chemotherapy        Side effects of this treatment include moder-
may be concerned about the effects of the          ate to severe fatigue, fever, chills, headaches,
treatment on their ability to have children.       muscle and joint aches, and mood changes.
The doctor and patients should discuss fertility       Monoclonal antibodies: Antibodies are
before treatment begins. Questions that might      normally produced by the immune system to
be asked include:                                  help fight infections. Similar antibodies called
   Will this treatment have any short- or long-    monoclonal antibodies can be made in the
term effect on my reproductive system? If so,      laboratory. Instead of attacking germs as usual
what is the effect and how long will it last?      antibodies do, some monoclonal antibodies
   • Is infertility a possible side effect of      can be designed to attack lymphoma cells.
     treatment (including ovarian failure)?        One product is called rituximab. Rituximab
   • Is there anything that can be done to         recognizes and attaches to a substance called
     prevent infertility before treatment?         CD20 that is found on the surface of some
   • Do any of the fertility preservation          types of lymphoma cells. This attachment kills
     options interfere with my cancer              the lymphoma cell. Patients usually receive 4
     treatment?                                    intravenous infusions over a period of about
   • If I become infertile, what are my            3 weeks. Common side effects are usually
     options for having a family?                  minor and limited to the time of infusion,
   • Can you refer me to a fertility specialist?   and may include chills, fever, nausea, rashes,
   • Once I finish treatment, how will I           fatigue, and headaches.
     know if I am infertile?                           Another man-made molecule approved
   • How long is it safe to wait to pursue         by the FDA is called denileukin diftitox. It is
     fertility options before beginning            used to treat T-cell skin lymphomas. It is made
     treatment for my cancer?                      by combining interleukin-2 (a protein that
   • Is my infertility short term or               attaches to some kinds of lymphocytes) and
     permanent?                                    diphtheria toxin, which kills cells.
                                                       Alemtuzumab is an antibody that is useful
Immunotherapy                                      in chronic lymphocytic leukemia (CLL) and
Immunotherapies use natural substances             even T-cell leukemias of the skin.
produced by the immune system. These sub-              Other new monoclonal antibodies are
stances may kill lymphoma cells, slow their        being studied in clinical trials.
growth, or activate the patient’s immune sys-          Radioimmunotherapy: Newer forms of
tem to fight the lymphoma more effectively.        monoclonal antibodies similar to rituximab
   Interferon: Interferon is a hormone-like        but with radioactive molecules attached to
protein naturally produced by white blood cells    them have also been developed for use in
to help the immune system fight infections.        lymphomas. The first to be approved by the
Some studies have suggested that interferon        FDA was ibritumomab tiuxetan, which is an
can cause some types of non-Hodgkin’s lym-         antibody that has radioactive yttrium attached
phomas to shrink or delay disease progression.     to it. It is used in patients with low grade or

                                                                                                      19
     follicular lymphoma that has returned after         with those of the patient. The donor is often
     treatment, and is also being studied in other       a brother or sister, or it can be a matched
     types of lymphoma. The second drug approved         unrelated donor. Allogeneic transplantation
     was tositumomab, which is an antibody with          is limited, however, because of the need for a
     radioactive iodine attached. It is also used        matched donor. Also, the side effects of this
     against low grade or follicular lymphoma            treatment are too severe for most people over
     after initial treatments no longer work. Both       55 to 60 years old.
     these drugs are being used for lymphomas                 In an autologous stem cell transplant, a
     that do not respond to other treatments. Their      patient’s own stem cells are removed from
     one disadvantage is they cannot be used             his or her bone marrow or bloodstream. With
     along with chemotherapy because they lower          some types of lymphoma that tend to spread
     blood counts.                                       to the bone marrow or blood, it may be hard to
                                                         collect stem cells alone without the presence
     Stem Cell Transplants                               of lymphoma cells. Even after treating the stem
     Stem cell transplants are used to treat lym-        cells in the lab to kill or remove lymphoma cells
     phoma patients when standard treatment              (purging), some remaining lymphoma cells may
     does not work. Although only a small number         be returned with the stem cell transplantation.
     of patients with NHL receive this treatment,             Stem cells collected from a donor or the
     this number is growing. Blood-forming stem          patient are frozen and stored. The patient
     cells are the earliest form of bone marrow cells.   then receives high-dose chemotherapy, and
     They can develop into normal blood cells            sometimes whole body radiation treatment
     such as red blood cells, white blood cells, and     as well. This destroys remaining cancer cells,
     platelets. They are given to patients after they    but it also kills all or most normal cells in the
     have had high-dose chemotherapy to replenish        bone marrow. After treatment, the frozen stem
     the bone marrow.                                    cells are thawed and returned to the body
         Stem cells can be taken from several bone       through an intravenous infusion. They then
     marrow aspirates, or they can be separated          make their way through the blood system to
     from the circulating (peripheral) blood by a        the bone marrow where they grow and divide
     method known as apheresis. Recent studies           to become the patient’s new blood-forming
     have shown that there may be an advantage           system.
     to using stem cells obtained by apheresis                A blood stem cell transplant is a complex
     instead of bone marrow aspiration. This has         treatment that can be life-threatening. If the
     become the usual way that doctors get stem          doctors think the patient may benefit from a
     cells.                                              transplant, the best place to have it done is at
         The 2 main kinds of stem cell transplants       a nationally recognized cancer center where
     are allogeneic and autologous. In an allogeneic     the staff has experience with the procedure and
     stem cell transplant, the stem cells come           with managing the recovery period. Patients
     from a donor whose cells are almost identical       should not hesitate to ask the doctor about


20
the number of times he or she has done this       kill the lymphoma. Only low doses of
procedure and their results with cases such       chemotherapy (usually a drug called fludara-
as theirs. Experience and knowledge are key       bine, which lowers a patient’s immunity) are
factors in providing the best care.               given. Then stem cells from a matched donor
    A stem cell transplant is very expensive      are given. Over time the donor cells take over
and can require a lengthy hospital stay. Side     the bone marrow and develop an immune
effects from a stem cell transplant are gener-    response to the lymphoma cells and destroy
ally divided into early and long-term effects.    them. The problem with this procedure is the
The early complications and side effects are      graft-versus-host disease, which harms the
basically the same as those caused by any         patient. Researchers are looking for ways to
other type of high-dose chemotherapy. They        stop the graft-versus-host response while
are caused by damage to the bone marrow           keeping the graft-versus-lymphoma effect.
and other rapidly growing tissues of the body.
    Complications and side effects that can       Supportive Care
last for a long time or not occur until years     Most of this document discusses ways to cure
after the transplant include:                     people with non-Hodgkin’s lymphoma or to
    • radiation damage to the lungs, causing      help them live longer. However, another
      shortness of breath                         important goal is to help you feel as well as
    • graft-versus-host disease, which occurs     you can and continue to do the things in life
      only in allogeneic (donor) transplants      that you want to do. Don’t hesitate to discuss
    • damage to the ovaries that can cause        your symptoms or how you are feeling with
      infertility and loss of menstrual periods   your cancer care team. There are effective and
    • damage to the thyroid gland that can        safe ways to treat symptoms you may be hav-
      cause problems with metabolism              ing, as well as most of the side effects caused
    • cataracts (damage to the lens of the        by treatment for non-Hodgkin’s lymphoma.
      eye that can affect vision)                    Pain is a concern for patients with
    • bone damage called aseptic necrosis. If     advanced cancer. Growth of the cancer around
      damage is severe, the patient will need     certain nerves may cause severe pain. It is
      to have part of the affected bone and       important that you tell your doctors if you
      the joint replaced.                         are having pain. For most patients, treatment
    • development of new cancers, mainly          with morphine or other so-called opioids
      leukemia several years later.               (medicines related to opium) will reduce the
    • infertility in male patients and early      pain considerably. For more information on
      menopause in female patients.               the treatment of cancer pain, contact the
                                                  ACS or NCCN to request a copy of the Cancer
   Nonmyeloablative transplants: This is a
                                                  Pain Treatment Guidelines for Patients.
special kind of transplant that takes advan-
tage of the donor cells’ immune response to



                                                                                                    21
     Complementary and                                     You can also help in your own recovery
     Alternative Therapies                             from cancer by making healthy lifestyle
     If you are considering any alternative or         choices. If you use tobacco, stop now.
     complementary treatments, please discuss          Quitting will improve your overall health,
     this openly with your cancer care team and        and the full return of the sense of smell may
     request information from the ACS or the           help you enjoy a healthy diet during recovery.
     National Cancer Institute. Some alternative       If you use alcohol, limit how much you drink.
     treatments can cause serious side effects.        Have no more than 1 or 2 drinks per day.
                                                       Good nutrition can help you get better after
                                                       treatment. Eat a nutritious diet, with plenty of
     Other Things to Consider                          fruits, vegetables, and whole grain foods. Ask
     During and After Treatment                        your cancer care team if you could benefit
                                                       from a special diet. They may have specific
     During and after treatment, you may be able       advice for people who have had radiation
     to hasten your recovery and improve your          therapy, chemotherapy, or surgery.
     quality of life by taking an active role. Learn       If you are being treated for cancer, be aware
     about the benefits and disadvantages of each      of the battle that is going on in your body.
     of your treatment options, and ask questions      Radiation therapy and chemotherapy add to
     if there is anything you do not understand.       the fatigue caused by the disease itself. To help
     Learn about and look out for side effects of      you with the fatigue, plan your daily activities
     treatment, and report these promptly to your      around when you feel your best. Get plenty of
     cancer care team so that they can take steps      sleep at night. Don’t be afraid to ask others for
     to reduce them or make them go away.              help. And ask your cancer care team about a
         Remember that your body is as unique as       daily exercise program to help you feel better.
     your personality and your fingerprints.               Surgery, radiation therapy, and chemo-
     Although understanding your cancer’s stage        therapy may sometimes affect your feelings
     and learning about your treatment options         about your body and may lead to specific
     can help predict what health problems you         physical problems that affect sexuality. Your
     may face, no one can say precisely how you        cancer care team can help with these issues,
     will respond to cancer or its treatment.          so don’t hesitate to share your concerns.
         You may have special strengths such as a          A cancer diagnosis and its treatment are
     history of excellent nutrition and physical       major life challenges, affecting you and
     activity, a strong family support system, or a    everyone who cares for you. Before you reach
     deep faith, and these strengths may make a        the point of feeling overwhelmed, consider
     difference in how you respond to cancer.          attending a meeting of a local support group.
     There are also experienced professionals in       If you need assistance in other ways, contact
     mental health services, social work services,     your hospital’s social service department or
     and pastoral services who may assist you in       the American Cancer Society for help in
     coping with your illness.                         contacting counselors or other services.

22
Clinical Trials                                      phase I study) and closely observed for an
                                                     effect on the cancer. The doctors will also
The purpose of clinical trials: Studies of           look for side effects.
promising new or experimental treatments                 Phase III clinical trials: Phase III studies
in patients are known as clinical trials.            involve large numbers of patients. One group
Researchers conduct studies of new treat-            will receive the standard (most accepted)
ments to answer the following questions:             treatment. The other group will receive the
   • Is the treatment helpful?                       new treatment. The study will be stopped if
   • How does this new type of treatment             the side effects of the new treatment are too
     work?                                           severe or if one group has had much better
   • Does it work better than other treat-           results than the others.
     ments already available?                            If you are in a clinical trial, you will have a
   • What side effects does the treatment            team of experts looking at you and monitoring
     cause?                                          your progress very carefully. The study is espe-
   • Are the side effects greater or less than       cially designed to pay close attention to you.
     the standard treatment?                             However, there are some risks. No one
   • Do the benefits outweigh the side               involved in the study knows in advance
     effects?                                        whether the treatment will work or exactly
   • In which patients is the treatment              what side effects will occur. That is what the
     most likely to be helpful?                      study is designed to discover. While most side
                                                     effects will disappear in time, some can be
    Types of clinical trials: A new treatment        permanent or even life threatening. Keep in
is normally studied in 3 phases of clinical trials   mind, though, that even standard treatments
before it is eligible for approval by the FDA        have side effects. Depending on many factors,
(Food and Drug Administration).                      you may decide to enroll in a clinical trial.
    Phase I clinical trials: The purpose of a            Deciding to enter a clinical trial:
phase I study is to find the best way to give a      Enrollment in any clinical trial is completely
new treatment and how much of it can be              up to you. Your doctors and nurses will explain
given safely. The treatment has been well            the risks and possible benefits of the study to
tested in laboratory and animal studies, but         you in detail and will give you a form to read
the side effects in patients are not completely      and sign indicating your understanding of
known. Although doctors are hoping to help           the study and your desire to take part. Even
patients, the main purpose of a phase I study        after signing the form and after the clinical
is to test the safety of the drug.                   trial begins, you are free to leave the study at
    Phase II clinical trials: These are designed     any time, for any reason. Taking part in the
to see if the drug works. Patients are usually       study will not prevent you from getting other
given the highest dose that doesn’t cause            medical care you may need.
severe side effects (determined from the



                                                                                                           23
        To find out more about clinical trials, ask      • If I am harmed as a result of the
     your cancer care team. Among the questions            research, what treatment would I be
     you should ask are:                                   entitled to?
        • What is the purpose of the study?              • What type of long-term follow-up care
        • What kinds of tests and treatments               is part of the study?
          does the study involve?                        • Has the treatment been used to treat
        • What does this treatment do?                     other types of cancers?
        • What is likely to happen in my case
                                                          The ACS offers a clinical trials matching
          with, or without, this new research
                                                      service that will help you find a clinical trial
          treatment?
                                                      that is right for you. Simply go to our web site
        • What are my other choices and their
                                                      (www.cancer.org) or call us at 1-800-ACS-2345.
          advantages and disadvantages?
                                                      You also can get a list of current National
        • How could the study affect my daily life?
                                                      Cancer Institute sponsored clinical trials by
        • What side effects can I expect from the
                                                      calling the NCI Cancer Information Service
          study? Can the side effects be con-
                                                      toll free at 1-800-4-CANCER or visiting the
          trolled?
                                                      NCI clinical trials Web site (www.cancer.gov/
        • Will I have to be hospitalized? If so,
                                                      clinical_trials/).
          how often and for how long?
        • Will the study cost me anything? Will
          any of the treatment be free?


                                               NOTES




24
              Treatment Guidelines

Decision Trees
The decision trees on the following pages represent treatment options for several
types of non-Hodgkin’s lymphoma. Each one shows you step-by-step how you and
your doctor can arrive at the choices you need to make about your treatment.

Keep in mind, this information is not meant to be used without the expertise of
your own doctor, who is familiar with your situation, medical history, and per-
sonal preferences. You may even want to review this booklet together with your
doctor, who can show you which of the decision trees apply to you. We’ve left
some blank spaces in the decision tree section for you or your doctor to add
notes about the treatments. You might also use this space to write down some
questions to ask your doctors about the treatments.

Participating in a clinical trial is an appropriate option for patients with most
stages of non-Hodgkin’s lymphoma. Taking part in a study does not prevent you
from getting other medical care you may need.

The NCCN guidelines are updated as new significant data become available. To
ensure you have the most recent version, consult the Web sites of the ACS
(www.cancer.org) or NCCN (www.nccn.org). You may also call the NCCN at 1-
888-909-NCCN or the ACS at 1-800-ACS-2345 for the most recent information on
these guidelines or on cancer in general.




                                                                                    25
                                        Treatment Guidelines for Patients


     Diagnosis




     Lymph node biopsy or bone marrow biopsy for
     diagnosis of lymphoma or leukemia
     Blood cell examination for leukemia
     Review by pathologist experienced in diagnosis of
     leukemia and lymphoma
     Special tests of blood, lymph node, or bone
     marrow to establish the exact type of lymphoma
     • Cell surface markers
     • Genetic studies (if needed)




     Chronic Lymphocytic Leukemia (CLL)/                 enlarged. The doctor will also examine the
     Small Lymphocytic Lymphoma (SLL)                    patient’s other organ systems and general
     The diagnosis is made by examining the bone         health and ask whether there has been any
     marrow and blood cells in the case of               fever or weight loss.
     leukemia and by a lymph node biopsy if it               Blood tests are done to check the blood
     appears to be lymphoma. A pathologist expe-         counts, liver function, kidney function, and
     rienced in diagnosing lymphomas should              calcium, uric acid, and LDH levels. These tests
     examine these samples. The diagnosis can be         provide information about the patient’s gen-
     confirmed by studying the cell surface markers.     eral health and how advanced the lymphoma
     A special test of the cells for Zap-70 can also     is. A blood test for beta-2-microglobulin may be
     help tell if the CLL will ever need treatment.      useful because it can sometimes also tell how
     A complete history and physical examination         advanced the lymphoma is. It can be elevated
     should be done. The doctor will want to             in advanced cases, as can the LDH.
     know if the lymph nodes, spleen, or liver are

26
                     Chronic Lymphocytic Leukemia (CLL)/
                      Small Lymphocytic Lymphoma (SLL)


     Evaluation                                                                                 Stage



     Doctor must do:
     • Physical examination
     • Determine general health and activity level                                              Stage I or II
                                                                                                (Lymphoma in one lymph
     • Determine if fever and/or weight loss is present
                                                                                                node group or in more
     • Complete blood count                                                                     than one node group on
     • Blood test of liver and kidney function and                                              same side of diaphragm)
       LDH, calcium, and uric acid levels
     Useful to do in some cases:
     • Measurement of blood immunoglobulins
     • If patient has anemia, count of young red
       blood cells
     • CT scan of chest
     • CT scan of abdomen and pelvis or ultrasound                                              Stage III or IV
       of abdomen                                                                               (Lymphoma on both sides
     • Discuss fertility issues and treatment                                                   of diaphragm or has
                                                                                                spread out of nodes to
     • Blood test for beta-2-microglobulin                                                      distant sites)
     • Chest x-ray
     • Bone marrow aspiration and biopsy



                                                          ©2005 by the National Comprehensive Cancer Network (NCCN) and the
                                                          American Cancer Society (ACS). All rights reserved. The information herein
                                                          may not be reproduced in any form for commercial purposes without the
                                                          expressed written permission of the ACS. Single copies of each page may be
                                                          reproduced for personal and non-commercial uses by the reader.




   Depending on a patient’s general health                scans may also be useful, particularly to look
and symptoms other tests may be done. If                  for enlarged lymph nodes and infections.
there is anemia, looking for young red cells in           Sometimes a bone marrow biopsy may be
the blood can tell if the red cells are being             needed. Treatment such as chemotherapy can
destroyed — something that can happen with                temporarily or permanently block the ability
this type of lymphoma. Often in CLL, the pro-             of the ovaries to make eggs and the testes to
duction of infection fighting immunoglobulins             produce sperm. This should be discussed
(antibodies) is defective and it is useful to             with patients who may want to have children
measure their levels, particularly if the patient         in the future.
has experienced infections. X-rays and CT

                                                                                                                                       27
                                     Treatment Guidelines for Patients


     Stage                                              Evaluation



     Stage I or II




                             Small lymphocytic            Determine whether there are reasons for
                             lymphoma                     treatment, such as:
                                                          • Eligible for a clinical trial
                             CLL–Good risk (only          • Immune system is destroying blood cells
                             high white blood             • Frequent serious infections
                             cell count present)
                                                          • Vital organ damage
                                                          • Low blood counts
     Stage III or IV                                      • Large tumor masses
                             CLL–Intermediate
                             risk (enlarged lymph         • Steady tumor growth over 6 months
                             nodes, spleen, or            • Lymphocyte count doubles within a year
                             liver present)
                                                          • Patient wants treatment



                             CLL–High risk (low red
                             blood cell and platelet
                             count present)




        If the diagnosis is stage I or II small        causing or will soon cause serious problems
     lymphocytic lymphoma (SLL), the affected          such as organ damage or serious infections
     lymph nodes can be treated with radiation         or there is steady growth, then treatment
     therapy, or no treatment may be needed. If the    should be given to avoid these problems. In
     lymphoma is more advanced or it is chronic        advanced stages where the red blood cell
     lymphocytic leukemia (CLL), then treatment        count and/or platelet count is low, treatment
     will be considered based on symptoms and          should be given.
     amount of cancer present and the wishes of the       If the decision is made to treat, drug ther-
     patient. Also, certain patients may be eligible   apy will be used. The drugs used most often
     to enter a clinical trial. If the lymphoma is     are chlorambucil, which is given as a pill, or

28
                Chronic Lymphocytic Leukemia (CLL)/
           Small Lymphocytic Lymphoma (SLL) (continued)


                            Initial Treatment


                             Either radiation therapy
                                                                    If lymph nodes
                             to lymph nodes, or
                                                                    are growing
                             Observation only




     No reasons
                             Observation until disease progresses
     for treatment




                             Treatment with single drug
                             • Purine, such as fludarabine with or without
                               rituximab
                             • Alkylating agent, such as cyclophosphamide
                               or chlorambucil
     Yes, there are          OR                                                                            Continued on
     reasons for                                                                                           next pages
                             Treatment with combination of drugs (no
     treatment
                             anthracycline or doxorubicin), such as
                             • Cyclophosphamide, vincristine, prednisone
                             • Cyclophosphamide, fludarabine, rituximab
                             OR
                             Radiation therapy


                                                    ©2005 by the National Comprehensive Cancer Network (NCCN) and the
                                                    American Cancer Society (ACS). All rights reserved. The information herein
                                                    may not be reproduced in any form for commercial purposes without the
                                                    expressed written permission of the ACS. Single copies of each page may be
                                                    reproduced for personal and non-commercial uses by the reader.




fludarabine, which is given intravenously.          along with rituximab. Another monoclonal
The monoclonal antibody rituximab can be            antibody that can be used is alemtuzumab. If
added to the fludarabine. Another option is a       frequent infections are a problem, this will be
combination of drugs, such as cyclophos-            treated with intravenous immunoglobulin.
phamide and vincristine given intravenously         Radiation therapy may be given to help con-
and prednisone given as a pill. Cyclophospha-       trol symptoms.
mide and fludarabine can be given together
                                                                                                                                 29
                                   Treatment Guidelines for Patients


     Response to Initial Treatment


     Lymphoma or
     leukemia has
     shrunk at
     least 50%




                                                      Determine whether there are reasons for
                                                      treamtent, such as:
                                                      • Eligible for a clinical trial
                                                      • Immune system is destroying blood cells
     Lymphoma or                                      • Frequent serious infections
     leukemia has                                     • Vital organ damage
     not shrunk or
                                                      • Low blood counts
     is growing
                                                      • Large tumor masses
                                                      • Steady tumor growth over 6 months
                                                      • Lymphocyte count doubles within a year
                                                      • Patient wants treatment




        If the lymphoma or leukemia responds to      lymphoma or leukemia doesn’t shrink, or if it
     the treatment by shrinking more than 50%,       shrinks and then grows back and there are
     then nothing further needs to be done. If the   reasons for treatment, then different drugs or

30
              Chronic Lymphocytic Leukemia (CLL)/
         Small Lymphocytic Lymphoma (SLL) (continued)


                                      Additional Treatment



                                                                                        If lymphoma
                                       Clinical trial or                                or leukemia
                                       observation                                      is growing




                                       Clinical trials (including studies of stem cell transplants in
                                       certain patients)
                                       OR
                                       Another treatment such as fludarabine or other purine
       Yes, there                      drug; if resistant to purines, use alkylator-based treatment
       are reasons                     (such as cyclophosphamide) or combination chemotherapy
       for treatment
                                       OR
                                       Local radiation therapy
                                       OR
                                       Antibody-based treatment (such as rituximab or
                                       alemtuzumab) with or without chemotherapy



       No reasons
                                       Observation
       for treatment




                                                 ©2005 by the National Comprehensive Cancer Network (NCCN) and the
                                                 American Cancer Society (ACS). All rights reserved. The information herein
                                                 may not be reproduced in any form for commercial purposes without the
                                                 expressed written permission of the ACS. Single copies of each page may be
                                                 reproduced for personal and non-commercial uses by the reader.




a different monoclonal antibody may be           nodes, or more intensive therapy, such as
given. Other options are simple treatment,       entering a clinical trial of a new drug or stem
such as radiation therapy to enlarged lymph      cell transplant.

                                                                                                                              31
                                       Treatment Guidelines for Patients


     Diagnosis




     Lymph node biopsy and/or bone marrow
     biopsy for diagnosis of lymphoma
     Review by pathologist experienced in
     diagnosis of lymphoma
     Special tests of blood, lymph node, or
     bone marrow to establish the exact type
     of lymphoma
     • Cell surface markers
     • Genetic studies (if needed)




     Follicular Lymphoma (Small or                   help identify the type of lymphoma.
     Mixed Cell)                                     Sometimes genetic studies are useful. A
     The diagnosis begins with surgery to remove     complete history and physical examination
     an enlarged lymph node or sometimes a bone      should be done. The doctor will want to
     marrow biopsy. A pathologist experienced in     know if lymph nodes, the spleen, or liver are
     diagnosing lymphomas should examine the         enlarged. The doctor will also examine other
     tissue. The diagnosis should be confirmed by    organ systems and determine general health
     studying the cell surface markers, which are    and ask about fever and weight loss.
     proteins on the surface of lyphoma cells that

32
                Follicular Lymphoma (Small or Mixed Cell)


     Evaluation



     Doctor must do:
     • Physical examination with special attention to areas
       with lymph nodes, back of throat, liver, and spleen
     • Check general health and activity
     • Ask about fever or weight loss
     • Complete blood count
     • Blood tests of kidney and liver function and LDH,
       calcium, and uric acid levels
     • Chest x-ray or CT scan                                                                                 Initial treatment
     • CT scan of abdomen and pelvis                                                                          (see next page)
     Useful to do in some cases:
     • Bone marrow aspiration and biopsy on one or both
       sides of pelvis may be useful
     • CT scan of the neck
     • Discuss effect of treatment on fertility
     • Blood test for beta-2-microglobulin and uric acid levels
     • Gallium scan or PET scan
     • Measurement of blood immunoglobulins




                                                           ©2005 by the National Comprehensive Cancer Network (NCCN) and the
                                                           American Cancer Society (ACS). All rights reserved. The information herein
                                                           may not be reproduced in any form for commercial purposes without the
                                                           expressed written permission of the ACS. Single copies of each page may be
                                                           reproduced for personal and non-commercial uses by the reader.




   Blood tests are done to check the blood                 ulin can also tell how advanced the lym-
counts, liver function, kidney function, and               phoma is. It can be elevated in advanced
calcium, uric acid, and LDH levels. All these              cases, as can the LDH. A chest x-ray and a
tests provide information about the patient’s              bone marrow test should be done if they have
general health and how advanced the lym-                   not been done already. A CT scan of the
phoma is. A blood test for beta-2-microglob-               abdomen and pelvis is also recommended.

                                                                                                                                        33
                                     Treatment Guidelines for Patients


     Stage                                                Initial Treatment


                                                           Radiation therapy to enlarged lymph
                                                           nodes
                                                           OR
                                                           Chemotherapy followed by radiation
     Stage I or II
                                                           therapy to enlarged lymph nodes
                                                           OR
                                                           Radiation therapy to enlarged lymph
                                                           nodes and nearby lymph nodes




                                                           Reasons for treatment:
                                                           • Eligible for a clinical trial
     Stage II with                                         • The lymphoma is causing symptoms
     very large lymph
                                                           • Vital organ damage possible
     nodes in the
     abdomen, or                                           • Low blood counts
     Stage III or IV                                       • Large tumor masses
                                                           • Steady tumor growth over 6 months
                                                           • Patient wants treatment




         If the lymphoma is stage I or II, it can be    has grown back after treatment, new treatment
     treated with radiation therapy to those            may be needed. Treatment will be considered
     lymph nodes. Chemotherapy may be given             based on symptoms and amount of cancer
     first. Or it can be treated with radiation ther-   present and the wishes of the patient. Also,
     apy that includes nearby lymph nodes.              certain patients may be eligible to enter a
     Another option in selected cases is no treat-      clinical trial. If the lymphoma is causing or will
     ment. If the lymphoma shrinks at least 50%         soon cause serious problems such as organ
     and doesn’t grow back, the patient can be fol-     damage or serious infections or there is steady
     lowed without any further treatment.               growth, then treatment should be given to
         If the lymphoma is stage II but the lymph      avoid these problems. In advanced stages where
     nodes are very large, or the lymphoma is stage     the red blood cell count and/or platelet count
     III or IV, or the lymphoma has not shrunk or       is low, treatment should be given.

34
                 Follicular Lymphoma (Small or Mixed Cell)
                                (continued)




                                    Doctor visits, exams,
     Lymphoma
                                    tests every 3 months
     has shrunk                                                                                 If lymphoma regrows
                                    for 1 year, then
     at least 50%
                                    every 3–6 months



     Lymphoma
     has not shrunk




                                                                                                If lymphoma regrows
                                    Doctor visits, exams,
     No reason                      tests every 3 months                                        There is transformation
     to treat                       for 1 year, then                                            to diffuse lymphoma
                                    every 3–6 months                                            (see page 38)
                                                                                                (biopsy may be useful)

                                     Radiation therapy to
                                     enlarged lymph nodes
                                                                                                More treatment
     There is reason                 OR                                                         depending on
     to treat                        Chemotherapy                                               response (see
                                     OR                                                         next page)
                                     Entry into a clinical trial




                                                       ©2005 by the National Comprehensive Cancer Network (NCCN) and the
                                                       American Cancer Society (ACS). All rights reserved. The information herein
                                                       may not be reproduced in any form for commercial purposes without the
                                                       expressed written permission of the ACS. Single copies of each page may be
                                                       reproduced for personal and non-commercial uses by the reader.




    If there are no reasons for treatment, then       nodes that are causing symptoms or
the patient can be observed with periodic             chemotherapy drugs These can be single
examinations and imaging tests.                       drugs such as rituximab, cyclophosphamide,
    If there are reasons for treatment, the           chlorambucil, or combinations of drugs such
patient may want to take part in a clinical           as cyclophosphamide, vincristine, and pred-
trial. Other options are radiation to lymph           nisone with possibly rituximab.

                                                                                                                                    35
                                   Treatment Guidelines for Patients


     Initial Response to Treatment




                                                                     Lymphoma starts to grow
                                Doctor visits, exams,
     Lymphoma                                                        OR
                                tests every 3 months
     has shrunk                                                      There is transformation to
                                for 1 year, then
     at least 50%                                                    diffuse lymphoma (see page 38)
                                every 3–6 months
                                                                     (biopsy may be useful)




     Lymphoma
     has not shrunk
     or is growing




        If the lymphoma has shrunk by 50% or            a clinical trial, or different chemotherapy can
     more, then more treatment isn’t needed at          be used. Other options are a radioactive
     this point. If the lymphoma begins to grow or      monoclonal antibody, such as ibritumomab
     has not shrunk by 50%, then more treatment         tiuxetan or tositumomab, or radiation to a
     may be needed, if reasons for treatment con-       large lymph node mass if one is present.
     tinue to exist. The treatment can be given in

36
                       Follicular Lymphoma – Grade 1 and 2
                         (Small or Mixed Cell) (continued)


                                                                             Additional Treatment




     Reasons for treatment:                 There is
                                                                             Follow-up
                                            no reason
     • Eligible for a clinical trial                                         doctor visits only
                                            to treat
     • The lymphoma is causing
       symptoms
     • Vital organ damage possible
     • Low blood counts                                                       Clinical trials
     • Large tumor masses                                                     OR
     • Steady tumor growth over                                               Chemotherapy
       6 months                             There is
                                                                              OR
     • Patient wants treatment              reason
                                            to treat                          Radioactive antibody treatment
                                                                              OR
                                                                              Radiation to area with lymph
                                                                              nodes causing symptoms




                                                                                          If lymphoma
                                                                                          has not shrunk
                                                                                          or is growing




                                                   ©2005 by the National Comprehensive Cancer Network (NCCN) and the
                                                   American Cancer Society (ACS). All rights reserved. The information herein
                                                   may not be reproduced in any form for commercial purposes without the
                                                   expressed written permission of the ACS. Single copies of each page may be
                                                   reproduced for personal and non-commercial uses by the reader.




    If the lymphoma shrinks by at least 50%, a     options can be considered. Another option is
clinical trial, which may include a stem cell      observation without any specific lymphoma
transplant, can be considered. Even if the         treatment.
lymphoma doesn’t shrink by 50%, these

                                                                                                                                37
                                  Treatment Guidelines for Patients


                                                               Treatment


                                                                Clinical trial
                                                                OR
                                                                Treatment with radioactive antibody
                                                                OR
                                 Several different              Chemotherapy with or without
                                 prior treatments               rituximab
                                                                OR
                                                                Radiation to area with lymph nodes
                                                                OR
     The lymphoma
     has transformed                                            Treatment directed toward symptoms
     to a diffuse large
     cell lymphoma

                                                                Combination chemotherapy that
                                                                includes an anthracycline agent
                                 Little or no                   - radiation may be added
                                 prior treatment                OR
                                                                Chemotherapy with or without
                                                                rituximab




         Many times, follicular lymphomas will       options include chemotherapy with or without
     transform into large B-cell lymphomas, that     rituximab, treatment with a radioactive anti-
     is, they may actually change from a slow-       body, radiation therapy, or, instead, treatment
     growing (indolent) type of lymphoma to an       directed at relieving symptoms.
     aggressive one. If many different treatments        If little treatment has been given before the
     have been tried before this happens, then a     follicular lymphoma transforms into a large
     clinical trial may be the best option. Other    B-cell lymphoma and the transformation is
38
                     Follicular Lymphoma – Grade 1 and 2
                       (Small or Mixed Cell) (continued)


        Response                                                Treatment




        Lymphoma shrinks                                         Consider stem cell transplant


                                                                 Consider stem cell transplant
        Lymphoma                                                 OR
        completely                                               Clinical trial
        disappears                                               OR
                                                                 No treatment



        Lymphoma                                                 Consider stem cell transplant
        shrinks by at                                            OR
        least 50%                                                Clinical trial


                                                                 Clinical trial

        Lymphoma                                                 OR
        doesn’t shrink,                                          Treatment with radioactive antibody
        or it grows                                              OR
                                                                 Treatment directed toward symptoms




                                                ©2005 by the National Comprehensive Cancer Network (NCCN) and the
                                                American Cancer Society (ACS). All rights reserved. The information herein
                                                may not be reproduced in any form for commercial purposes without the
                                                expressed written permission of the ACS. Single copies of each page may be
                                                reproduced for personal and non-commercial uses by the reader.




in a single area, then combination chemo-       50%, then high-dose chemotherapy followed
therapy that includes an anthracycline drug     by a stem cell transplant or participation in a
and perhaps radiation therapy to the site are   clinical trial might be suggested. If not, in
suggested along with rituximab in some          addition to these options, treatment with a
cases. If the lymphoma shrinks by at least      radioactive antibody might be useful.

                                                                                                                             39
                                        Treatment Guidelines for Patients


     Diagnosis                                Evaluation

                                              Doctor must do:
                                              • Physical examination
                                              • Complete blood count                 Stage IE, H. pylori
                                                                                     infection is present
                                              • Blood tests of kidney and
     Biopsy of stomach — repeat if              liver function and LDH,
     the biopsy isn’t deep enough               calcium, and uric acid levels
     to make a diagnosis of                   • Chest x-ray or CT chest
     lymphoma
                                              • CT scan of abdomen and
     Review by pathologist                                                           Stage IE or II, no
                                                pelvis
     experienced in diagnosis of                                                     H. pylori infection
                                              • Endoscopy with multiple
     lymphoma
                                                biopsies
     Special tests of biopsy specimen
     to establish the exact type of           Useful to do in some cases:
     lymphoma                                 • Ultrasound of stomach
     • Cell surface markers                     through the gastroscope
     • Genetic studies (if needed)
                                              • Other tests for H. pylori
     Test for presence of                       infection (blood and breath)
     Helicobacter pylori infection
                                              • X-ray of stomach and small
                                                intestine
                                              • Bone marrow aspiration               Stage III or IV
                                                and biopsy
                                              • Neck CT




     Gastric MALT Lymphoma                                    A complete physical examination is done
     The diagnosis begins with a biopsy of the stom-      along with blood tests to check the blood
     ach. This is done by passing a lighted tube into     counts, liver function, kidney function, and
     the stomach from the mouth (endoscopy or             calcium, uric acid, and LDH levels. A chest x-
     gastroscopy). The biopsy needs to be deep            ray and CT scan of the abdomen and pelvis
     enough so that lymphoma cells can be seen. A         are also taken. Another test that may be use-
     pathologist experienced in diagnosing lym-           ful is an ultrasound of the stomach through
     phomas should examine the biopsy sample. It          the gastroscope or endoscope to measure the
     should also be tested for cell surface markers       thickness of the stomach wall. This may tell
     to confirm the diagnosis. Genetic studies may        how large the lymphoma is. X-rays may be
     be needed also. Finally, the stomach specimen        needed to see if the lymphoma has invaded
     should be tested for the presence of bacteria        the rest of the intestines. A bone marrow exam
     called Helicobacter pylori (H. pylori).              can tell if the lymphoma has spread there.

40
                               Gastric MALT Lymphoma


                           Initial Treatment                   Restaging



                          Standard antibiotic
                          treatment for H. pylori

                                                             Repeat gastroscopy                          See next page
                                                             and biopsy at 3                             for 3-month
                          Standard antibiotic                months to look for                          restaging and
                          treatment for H. pylori            H. pylori infection                         reevaluation
                                                             and lymphoma                                with endoscopy
                          OR
                          Low-dose radiation
                          therapy



                          Chemotherapy with
                          one or several drugs               Repeat endoscopy
     There are            OR                                 If lymphoma has come
     reasons for                                             back, treat the same as
                          Radiation therapy                  follicular lymphoma
     treatment
                          to stomach and                     (see page 34)
                          surrounding area



     No reasons for
                          Careful follow-up
     treatment

                                                    ©2005 by the National Comprehensive Cancer Network (NCCN) and the
                                                    American Cancer Society (ACS). All rights reserved. The information herein
                                                    may not be reproduced in any form for commercial purposes without the
                                                    expressed written permission of the ACS. Single copies of each page may be
                                                    reproduced for personal and non-commercial uses by the reader.




    Treatment with only antibiotics is suggested    involvement, chemotherapy may be given if
if the lymphoma is confined to the stomach          there are reasons for treatment. Reasons for
and infection with H. pylori is found. If the       treatment are: presence of bleeding from
lymphoma is a little more advanced and has          stomach, vital organ damage, very large
spread to surrounding lymph nodes, radiation        tumor, steady growth of lymphoma, symp-
therapy may be added. After treatment,              toms, or patient wants treatment or is willing
endoscopy with biopsy should be repeated            to enroll in a clinical trial. For stages III and
in 3 months. For more advanced stages III or        IV, the lymphoma may be treated as if it were
IV with widespread lymph node or organ              a follicular lymphoma.

                                                                                                                                 41
                                   Treatment Guidelines for Patients


     3-Month Restaging and Reevaluation with Follow-Up Endoscopy




                                          No H. pylori
                                          or lymphoma




                                                                                   No symptoms


                                          No H. pylori,
     Endoscopy                            but lymphoma
     with biopsy                          is still present
                                                                                   Symptoms
                                                                                   are present
                                          H. pylori is still
                                          found, but no
                                          lymphoma


                                                                                   Lymphoma is
                                          H. pylori and                            not growing
                                          lymphoma are
                                          still present                            Lymphoma
                                                                                   is growing




        After 3 months, a repeat endoscopy should         3 more months of observation is suggested or
     be done. If neither lymphoma nor H. pylori is        radiation therapy can be given to the stom-
     found, no further treatment is needed. If the        ach. If there are symptoms, radiation therapy
     H. pylori is gone but lymphoma persists, then        should be given. If the lymphoma is gone but

42
                   Gastric MALT Lymphoma (continued)


                         Additional Treatment




                          Careful
                          follow-up only




                          Follow-up without
                          treatment for
                          another 3 months
                          OR
                          Radiation therapy
                                                                                           See next page for
                                                                                           6-month restaging
                                                                                           and reevaluation
                          Radiation therapy




                          Second-line course
                          of antibiotics with
                          different drugs




                          Radiation therapy




                                                  ©2005 by the National Comprehensive Cancer Network (NCCN) and the
                                                  American Cancer Society (ACS). All rights reserved. The information herein
                                                  may not be reproduced in any form for commercial purposes without the
                                                  expressed written permission of the ACS. Single copies of each page may be
                                                  reproduced for personal and non-commercial uses by the reader.




H. pylori persists, then another course of dif-   given if the lymphoma is not growing. If it is
ferent antibiotics should be given. If both the   growing, then radiation therapy to the stom-
lymphoma and H. pylori are still present, a       ach and surrounding area is suggested.
second course of different antibiotics can be

                                                                                                                               43
                                       Treatment Guidelines for Patients


     6-Month Restaging and Reevaluation with Follow-Up Endoscopy



                                No H. pylori             Follow-up
                                or lymphoma              without treatment



                                                         Radiation therapy if
                                                         not given before
                                No H. pylori             OR
                                but lymphoma             If radiation has been
                                is still present         given, treat same as
                                                         follicular lymphoma          Repeat
     Endoscopy with                                      (see page 34)                endoscopy
     biopsy at 6                                                                      (The exact
     months                                                                           timing of
                                                                                      a repeat
                                H. pylori is still       Consider treatment
                                                                                      endoscopy is
                                found, but no            with different
                                                                                      not known)
                                lymphoma                 antibiotics



                                                         Radiation therapy if
                                                         not given before
                                H. pylori and            OR
                                lymphoma are             If radiation has been
                                still present            given, treat same as
                                                         follicular lymphoma
                                                         (see page 34)




         Another endoscopy and a biopsy should be        ferent antibiotics is suggested. If both are
     done at the 6-month follow-up. If no H. pylori      found, then radiation should be given to the
     or lymphoma is found in the stomach, no             stomach and surrounding area if this has not
     treatment is needed. If the H. pylori is gone but   already been done. If radiation has been
     lymphoma persists, then radiation can be given      given, then the lymphoma should be treated
     if it has not been given before. If there has       with chemotherapy like a follicular lymphoma.
     been radiation therapy, another option is to            Endoscopy and biopsy should be repeated
     treat the lymphoma as a follicular lymphoma         again, although the exact timing is not known.
     with chemotherapy. If the lymphoma is gone          If the lymphoma has not gotten smaller and
     but H. pylori persists, another course of dif-      radiation therapy has not been given, then

44
                   Gastric MALT Lymphoma (continued)




                                                         Lymphoma                                Treat like follicular
                                                         comes back                              lymphoma (see
                                                         after radiation                         page 34)

   Lymphoma              Follow-up every 3
   is completely         months for 1 year,
   gone                  then every 3–6 months                                                  The lymphoma
                                                                                                has spread out-
                                                                                                side the stomach
                                                         Lymphoma
                                                         comes back
                                                         after antibiotics
                                                                                                The lymphoma
                                                                                                is still only in
                                                                                                the stomach




                                                                                                 Radiation therapy



                            Radiation
                                                           Treat like follicular lymphoma
                            therapy had
                                                           (see page 34)
   Lymphoma                 been given
   has not
   gotten
   smaller                  Antibiotics
                            have been                      Treat with radiation therapy
                            given



                                                 ©2005 by the National Comprehensive Cancer Network (NCCN) and the
                                                 American Cancer Society (ACS). All rights reserved. The information herein may
                                                 not be reproduced in any form for commercial purposes without the expressed
                                                 written permission of the ACS. Single copies of each page may be reproduced
                                                 for personal and non-commercial uses by the reader.




the lymphoma is treated like a follicular        chemotherapy like a follicular lymphoma. If the
lymphoma. If antibiotics have been given,        lymphoma returns after antibiotic therapy,
then it is treated with radiation therapy.       radiation therapy should be given. If it has
    If the lymphoma is gone, no more treatment   spread to a site away from the stomach, it
is needed. Repeat endoscopies and biopsies       should be treated as a follicular lymphoma
are suggested. If the lymphoma returns after     with chemotherapy.
radiation therapy, it should be treated with
                                                                                                                                  45
                                    Treatment Guidelines for Patients


     Stage                                                         Treatment




                                                                    Radiation therapy
                                                                    OR
     Stage IE–II                                                    Surgery may be used for
     (localized to one                                              lymphoma in lung, breast
     area of the body)                                              (plus radiation therapy),
                                                                    skin, thyroid, or small or
                                                                    large intestine




     Stage III–IV                                                   Radiation therapy
     (Lymph nodes on both
                                                                    OR
     sides of diaphragm
     and/or lymphoma is                                             Treat like follicular
     outside lymph nodes                                            lymphoma (see reasons for
     in several sites)                                              treatment on page 34)




     Stage IE–IV
     MALT lymphomas                                                 Treat like diffuse large B-cell
     occurring along with                                           lymphoma (see page 52)
     large cell lymphoma




     Nongastric MALT Lymphoma/                         that endoscopy is not done. An expert
     Marginal Zone Lymphoma                            pathologist should review the biopsy sample.
     The usual sites of nongastric MALT lym-           The diagnosis should be confirmed by testing
     phomas are salivary glands, skin, breast, small   the cell surface markers and perhaps by
     or large intestine, thyroid, tissue around the    genetic studies. Then the doctor should take
     eye, and lung.                                    a medical history, perform a physical exami-
        Diagnosis and work-up are the same as          nation, and order the blood and imaging
     those for gastric MALT lymphoma except            tests to stage the lymphoma.

46
    Nongastric MALT Lymphoma/Marginal Zone Lymphoma




                                                                                        Radiation therapy
                                           Lymphoma comes                               OR
                                           back in same site                            Treat like follicular
     Follow-up doctor visits                                                            lymphoma (see page 34)
     and tests every 3 months
     for 1 year, then every
     3–6 months
                                           Lymphoma comes                               Treat like follicular
                                           back in distant sites                        lymphoma (see page 34)




                                                        ©2005 by the National Comprehensive Cancer Network (NCCN) and the
                                                        American Cancer Society (ACS). All rights reserved. The information herein may
                                                        not be reproduced in any form for commercial purposes without the expressed
                                                        written permission of the ACS. Single copies of each page may be reproduced
                                                        for personal and non-commercial uses by the reader.




    If the lymphoma is stage IE or II (localized),     distant site, it should be treated with chemo-
then local therapy is all that is needed.              therapy as a follicular lymphoma.
Radiation therapy is used most often, but                  If the lymphoma is more widespread, stage
surgery is another option in certain circum-           III or IV, then it should be treated the same
stances. If the lymphoma comes back in the             as a follicular lymphoma. If any large cell
same site after surgery, radiation can be used         lymphoma is found, then it should be treated
or it can be treated with chemotherapy as for          like a diffuse large B-cell lymphoma.
a follicular lymphoma. If it comes back in a

                                                                                                                                         47
                                     Treatment Guidelines for Patients


     Diagnosis                                   Evaluation


                                          Doctor must do:
                                          • Physical examination with special
                                            attention to areas with lymph nodes,
                                            back of throat, liver, and spleen
                                                                                           Stage I or II
                                          • Check general health and activity              (localized
                                          • Ask about fever or weight loss                 mantle cell
     Lymph node biopsy (not               • Complete blood count                           lymphoma
     fine needle aspiration) or                                                            is rare)
                                          • Blood tests of kidney and liver
     bone marrow biopsy for                 function and LDH and calcium
     diagnosis of lymphoma
                                          • Chest x-ray or CT scan of chest
     Review by pathologist
     experienced in diagnosis of          • CT scan of abdomen and pelvis
     lymphomas. Repeat biopsy             • Bone marrow aspiration and biopsy
     if specimen inadequate for           • Colonoscopy
     diagnosis
     Special tests of biopsy              Useful in some cases:
                                                                                           Stage III
     specimen to establish the            • Look into esophagus and stomach
                                                                                           or IV
     exact type of lymphoma                 with endoscope
     • Cell surface markers               • CT scan of the neck
     • Genetic studies (if needed)
                                          • Upper gastrointestinal x-ray or
                                            endoscopy
                                          • Blood uric acid levels
                                          • Discuss effect of treatment on fertility
                                          • Blood test for beta-2-microglobulin
                                          • Spinal tap to look for lymphoma in
                                            spinal fluid




     Mantle Cell Lymphoma                                 if lymph nodes, the spleen, or the liver is
     The diagnosis is made by lymph node biopsy           enlarged. The doctor will also look at other
     or, sometimes, bone marrow. A pathologist            organ systems and the patient’s general health
     experienced in diagnosing lymphomas should           and ask about systemic symptoms such as
     examine the sample. The diagnosis should be          fever or weigh loss.
     confirmed by studying the cell surface markers.          Blood tests are done to check the blood
     Sometimes genetic studies are useful. A com-         counts, liver function, kidney function, and
     plete medical history and physical examination       calcium, uric acid, and LDH levels. All these
     should be done. The doctor will want to know         tests provide information about the patient’s

48
                                Mantle Cell Lymphoma


        Initial Treatment                       Response                                     Additional
                                                                                             Treatment


                                                Lymphoma
         Clinical trial                         completely                                    Observation
         OR                                     disappears

         Combined radiation
         therapy and combination
         chemotherapy                                                                        If lymphoma
         OR                                                                                  comes back
         Radiation therapy alone



                                                                                              Clinical trial
         Clinical trial                         Lymphoma                                      OR
         OR                                     shrinks by                                    Different treatment
                                                more than 50%                                 mainly to relieve
         Combined chemotherapy
                                                                                              symptoms and
         with or without rituximab
                                                                                              improve well-being
         OR                                     Lymphoma                                      • Radiation therapy
         Observation (no treatment)             doesn’t shrink
                                                                                              • Combination
         in certain cases                       much or keeps
                                                                                                chemotherapy
                                                growing
                                                                                                that includes a
                                                                                                purine-like drug



                                                  ©2005 by the National Comprehensive Cancer Network (NCCN) and the
                                                  American Cancer Society (ACS). All rights reserved. The information herein
                                                  may not be reproduced in any form for commercial purposes without the
                                                  expressed written permission of the ACS. Single copies of each page may be
                                                  reproduced for personal and non-commercial uses by the reader.




general health and how advanced the lym-              Other tests may be done such as endoscopy
phoma is. A chest x-ray or CT scan of the         examination of the stomach and esophagus.
chest and a bone marrow test are done if they     A CT of the neck may be helpful if there is
have not been done already. A CT scan of the      suspicion of enlarged lymph nodes in this
abdomen and pelvis is also recommended.           area. Blood tests for uric acid and beta-2-
Also, because this lymphoma may invade the        microglobulin may also be helpful. A spinal
lower intestines a colonoscopy should also        tap may be helpful. Finally, because treatment
be done.                                          may affect fertility, this needs to be discussed
                                                  if the patient wants to have a family.

                                                                                                                               49
                                       Treatment Guidelines for Patients




         No cure for mantle cell lymphoma has been          with radiation added if the disease appears to
     established; however, several treatment options        be localized, or radiation alone. In patients
     are available. One option is participation in a        with more advanced disease, rituximab may
     clinical trial. Clinical trials in this type of lym-   be added to chemotherapy. For patients under
     phoma often involve stem cell transplants.             65, high-dose chemotherapy followed by a
     Other options are combination chemotherapy             stem cell transplant may be the best option.



                                                     NOTES




50
                   Mantle Cell Lymphoma (continued)




   Because this can sometimes be a slow            If the disease relapses or never responds,
growing lymphoma, if there are no symptoms,    further therapy might involve entry into a
observation without treatment is another       clinical trial. If not, chemotherapy (including
option for select patients. Treatment can be   a purine-like drug) or radiation is useful in
started when symptoms begin or the patient     maintaining or improving well-being.
appears to be getting worse.



                                         NOTES




                                                                                                 51
                                        Treatment Guidelines for Patients


     Diagnosis



     This guideline applies whenever diffuse large B-cell lymphoma is present
     along with follicular, gastric MALT, and nongastric MALT lymphomas.
     It also applies to anaplastic large cell and peripheral T-cell lymphomas.




     Lymph node biopsy or bone marrow biopsy for diagnosis of lymphoma
     Review by pathologist experienced in diagnosis of lymphomas.
     Repeat biopsy if specimen inadequate for diagnosis
     Special tests of biopsy specimen to establish the exact type of lymphoma
     • Cell surface markers
     • Genetic studies (if needed)




     Diffuse Large B-Cell Lymphoma                             organ systems, ask about the patient’s general
     (This section also applies to anaplastic large            health and whether there has been any fever
     cell lymphomas, most peripheral T-cell lym-               or weight loss.
     phomas, and follicular or MALT lymphomas                      Blood tests are done to check the blood
     that contain diffuse large B-cell lymphoma.)              counts, liver function, kidney function, and
         The diagnosis is made by lymph node                   calcium, uric acid, beta-2-microglobulin, and
     biopsy or, sometimes, bone marrow or other                LDH levels. All these tests provide informa-
     tissue. A pathologist experienced in diagnosing           tion about the patient’s general health and
     lymphomas should examine the sample. The                  how advanced the lymphoma is. A chest x-ray
     diagnosis should be confirmed by studying                 or CT scan of the chest is done, as well as a
     the cell surface markers. Sometimes genetic               bone marrow test if it hasn’t been done
     studies are useful. A complete medical history            already. A CT scan of the abdomen and pelvis
     and physical examination should be done.                  is also recommended. The International
     The doctor will want to know if lymph nodes               Prognostic Index is calculated. Finally, heart
     are enlarged or if the spleen or liver is                 function may be tested with a MUGA scan.
     enlarged. The doctor will also examine other              This may be needed because most chemo-

52
                            Diffuse Large B-Cell Lymphoma


      Evaluation


      Doctor must do:
      • Physical examination with special attention to areas with lymph nodes,
        back of throat, liver, and spleen
      • Check general health and activity
      • Ask about fever or weight loss
      • Complete blood count
      • Blood tests of kidney and liver function and LDH, calcium, and uric
        acid levels
      • Chest x-ray
      • CT scans of chest, abdomen, and pelvis
      • Bone marrow aspiration and biopsy of one or both sides of pelvic bone
                                                                                                                      See initial
      • Calculate International Prognostic Index (IPI) (see page 16)
                                                                                                                      treatment on
      • Blood test for beta-2-microglobulin                                                                           next page
      • Measure heart function with radioactive scan (MUGA) or echocardiogram

      Useful in some cases:
      • Gallium scan or PET scan
      • CT scan of the neck
      • CT or MRI of head
      • Discuss the effect of treatment on fertility
      • Stool test for blood if there is anemia
      • Test for HIV (AIDS virus)
      • Spinal tap to test fluid for lymphoma cells if lymphoma is in
        sinuses, testicles, near the eye or spine, or if HIV test is positive



                                                              ©2005 by the National Comprehensive Cancer Network (NCCN) and the
                                                              American Cancer Society (ACS). All rights reserved. The information herein
                                                              may not be reproduced in any form for commercial purposes without the
                                                              expressed written permission of the ACS. Single copies of each page may be
                                                              reproduced for personal and non-commercial uses by the reader.




therapy regimens for this type of lymphoma                    enlarged lymph nodes in this area. A spinal
include an anthracycline drug like doxorubicin.               tap may be helpful as might a CT or MRI scan
Anthracyclines can damage the heart.                          of the brain. HIV testing might be indicated
   Other tests that may be useful are a gal-                  in some patients. Finally, because treatment
lium scan or a PET scan. A CT of the neck                     may affect fertility, this needs to be discussed
may be helpful if there is suspicion of                       if the patient wants to have a family.
                                                                                                                                           53
                                   Treatment Guidelines for Patients


     Stage

                                                                                   Outlook poorer:
                                                                                   • High LDH
                                                                                   • Stage II
                                       Tumor smaller than                          • Over age 60
                                       10 cm (4 inches)                            • Very sick from
                                                                                     lymphoma


                                                                                   Outlook good
     Stage I or II




                                       Tumor larger than
                                       10 cm (4 inches)




                                       Low IPI (0–1)



     Stage III or IV


                                       High IPI
                                       (2 or greater)




        If the lymphoma is stage I or II, treatment        cycles of chemotherapy are given, followed
     depends on it size. For tumors smaller than           by radiation.
     10 centimeters (4 inches), in patients with a             Stages III and IV patients with a low
     poor outlook, chemotherapy with CHOP                  International Prognosis Index (IPI) are treated
     (cyclophosphamide, doxorubicin, vincristine           mainly with CHOP chemotherapy, usually with
     and prednisone) is recommended. Rituximab             added rituximab. If the IPI is high, a clinical
     and/or intermediate-dose radiation (15 to 20          trial, with perhaps a stem cell transplant,
     treatments) may be added. The same treat-             may be preferred because the outlook is not
     ment is recommended if the tumor is larger            good. Otherwise CHOP and rituximab may
     except that radiation therapy should be given.        be given with rituximab added for patients
        For patients with a good outlook whose             over 60 and optional for younger patients. If
     tumor is smaller than 4 inches, only 3 to 4           the lymphoma is in the bone marrow, nasal
54
              Diffuse Large B-Cell Lymphoma (continued)


     Treatment


      CHOP chemotherapy for 6–8 cycles, with or
      without rituximab, with or without medium-
      dose radiation therapy to lymph node area



      CHOP chemotherapy for 3–4 cycles, with                                                          See next page
      or without rituximab, plus medium-dose                                                          for continued
      radiation therapy to lymph node area                                                            treatment



      CHOP chemotherapy for 6–8 cycles, with
      or without rituximab, plus medium-dose
      radiation therapy to lymph node area



      CHOP chemotherapy for 6–8 cycles
      plus rituximab


                                                                                                      See page 58
      Clinical trial (may include high-dose
                                                                                                      for continued
      treatment and stem cell transplantation)
                                                                                                      treatment
      OR
      CHOP chemotherapy for 6–8 cycles plus
      rituximab for patients over 60 (optional
      for younger patients)


                                                   ©2005 by the National Comprehensive Cancer Network (NCCN) and the
                                                   American Cancer Society (ACS). All rights reserved. The information herein
                                                   may not be reproduced in any form for commercial purposes without the
                                                   expressed written permission of the ACS. Single copies of each page may be
                                                   reproduced for personal and non-commercial uses by the reader.




sinuses, testicles, or near the spinal cord, it    down products of the dead lymphoma cells,
may spread to the central nervous system.          These breakdown products can interfere
Therefore, chemotherapy may be given into          with heart and kidney function. Drugs such as
the spinal fluid.                                  allopurinol or rasburicase and large amounts
   The doctor must consider the possibility        of intravenous fluids containing sodium
that chemotherapy might quickly destroy the        bicarbonate can prevent this problem.
lymphoma. This can flood the body with break-
                                                                                                                                55
                                   Treatment Guidelines for Patients


                                    Response                          Further Treatment




                                    Lymphoma
                                                                       Complete planned
                                    has completely
                                                                       treatment
                                    disappeared




                                                                       Complete treatment
                                    Lymphoma has                       with high doses of
     Stage I & II                                                      radiation therapy
                                    shrunk by more
     Repeat all
                                    than half but                      OR
     positive tests
                                    not disappeared                    Consider a clinical trial
                                                                       or stem cell transplant




                                    Lymphoma has
                                                                       New treatment
                                    not shrunk or
                                                                       (see page 60)
                                    is growing




        After about 3 to 4 courses of chemotherapy,      For stages I and II lymphoma, if these tests
     the doctor may repeat the imaging tests that     show that the lymphoma has disappeared
     showed the lymphoma. This will show if the       (sometimes scar tissue is left behind, which can
     lymphoma is responding to treatment.             be seen with a PET or gallium scan or repeat

56
             Diffuse Large B-Cell Lymphoma (continued)


                                           Response                                             Follow-Up



                                                                                                Doctor visits
                                          Lymphoma                                              every 3 months
                                          has completely                                        for 2 years, then
                                          disappeared                                           every 6 months
                                                                                                for 3 years




                                                                                                If lymphoma
                                          Lymphoma has                                          comes back
       After treatment is
                                          shrunk by more
       complete, repeat
                                          than half but
       all positive tests
                                          not disappeared



                                                                                                New treatment
                                                                                                (see page 60)




                                          Lymphoma
                                          has not shrunk
                                          or is growing




                                                 ©2005 by the National Comprehensive Cancer Network (NCCN) and the
                                                 American Cancer Society (ACS). All rights reserved. The information herein
                                                 may not be reproduced in any form for commercial purposes without the
                                                 expressed written permission of the ACS. Single copies of each page may be
                                                 reproduced for personal and non-commercial uses by the reader.




biopsy), the CHOP chemotherapy should be        chemotherapy and a stem cell transplant
continued as planned along with any planned     might be considered. If the lymphoma hasn’t
radiation. If the lymphoma has shrunk by        shrunk by at least half, then high-dose
more than half but hasn’t disappeared, more     chemotherapy and a stem cell transplant
intensive radiation may be given or high-dose   might be considered for these patients.

                                                                                                                              57
                                     Treatment Guidelines for Patients


                                      Response                          Further Treatment




                                      Lymphoma
                                                                         Continue CHOP to
                                      has completely
                                                                         a total of 6–8 cycles
                                      disappeared




                                      Lymphoma has                       Continue CHOP to a
     Stage III,IV                                                        total of 6–8 cycles
                                      shrunk by more
     Repeat all
                                      than half but                      OR
     positive tests
                                      not disappeared                    Consider a clinical trial




                                      Lymphoma has
                                                                         New treatment
                                      not shrunk or
                                                                         (see page 60)
                                      is growing




        For stages III and IV lymphoma, if these tests   as planned. If the lymphoma has shrunk by
     show that the lymphoma has disappeared,             more than half but hasn’t disappeared, either
     the CHOP chemotherapy should be continued           the CHOP chemotherapy may be continued,

58
              Diffuse Large B-Cell Lymphoma (continued)


                                               Response                                             Follow-Up



                                                                                                    Doctor visits
                                              Lymphoma                                              every 3 months
                                              has completely                                        for 2 years, then
                                              disappeared                                           every 6 months
                                                                                                    for 3 years




                                                                                                    If lymphoma
                                              Lymphoma has                                          comes back
        After treatment is
                                              shrunk by more
        complete, repeat
                                              than half but
        all positive tests
                                              not disappeared



                                                                                                    New treatment
                                                                                                    (see page 60)




                                              Lymphoma
                                              has not shrunk
                                              or is growing




                                                     ©2005 by the National Comprehensive Cancer Network (NCCN) and the
                                                     American Cancer Society (ACS). All rights reserved. The information herein
                                                     may not be reproduced in any form for commercial purposes without the
                                                     expressed written permission of the ACS. Single copies of each page may be
                                                     reproduced for personal and non-commercial uses by the reader.




or a clinical trial of different treatment may be   high-dose chemotherapy and a stem cell
recommended. If the lymphoma hasn’t shrunk          transplant may be recommended to eligible
by at least half, then new treatment such as        patients.

                                                                                                                                  59
                                   Treatment Guidelines for Patients


     Relapse or resistant               Additional Treatment                           Second
     to first treatment                                                                Response




                                         Different chemotherapy                       Lymphoma is
     Candidate
                                         regimen with drugs not                       completely gone
     for high-dose
                                         used before, with or                         or shrunk by
     therapy
                                         without rituximab                            more than half




                                         Clinical trial
                                                                                      Lymphoma has
     Not a candidate                     OR
                                                                                      not shrunk by
     for high-dose                       Individual treatment                         more than half
     therapy                             agreed on by doctor                          or is growing
                                         and patient




        If the patient is a candidate for high-dose       If the lymphoma responds by shrinking by
     chemotherapy, he or she should first be given        more than half, then the transplant can take
     a new chemotherapy regimen such as ICE,              place. If it doesn’t shrink that much, then a
     DHAP, or MIME. Rituximab may also be given.          transplant isn’t considered appropriate.

60
              Diffuse Large B-Cell Lymphoma (continued)


                                Additional                                                                    Second
                                (High-Dose) Therapy                                                           Relapse


                                         High-dose chemotherapy
                                         plus stem cell transplant,
                                         either from patient or
        Candidate                        from closely matched
        for high-dose                    donor, with or without                                             Clinical Trial
        therapy                          radiation
                                         OR
                                         Clinical trial


                                                                                                            Clinical Trial
                                                                                                            OR
        Not a candidate                                                                                     Individual
        for high-dose                                                                                       treatment
        therapy                                                                                             agreed on
                                                                                                            by doctor
                                                                                                            and patient




                                                                                                            Clinical Trial
                                                                                                            OR
                                                                                                            Supportive care
                                                                                                            to improve
                                                                                                            quality of life




                                                          ©2005 by the National Comprehensive Cancer Network (NCCN) and the
                                                          American Cancer Society (ACS). All rights reserved. The information herein
                                                          may not be reproduced in any form for commercial purposes without the
                                                          expressed written permission of the ACS. Single copies of each page may be
                                                          reproduced for personal and non-commercial uses by the reader.




   For patients who are not candidates for                treatment program decided on with the doc-
high-dose chemotherapy and stem cell trans-               tor, or treatment aimed mainly at relieving
plant, the options are a clinical trial, another          symptoms.

                                                                                                                                       61
                                       Treatment Guidelines for Patients


     Diagnosis




     Lymph node biopsy or bone marrow
     biopsy for diagnosis of lymphoma
     Review by pathologist experienced in
     diagnosis of lymphomas. Repeat biopsy if
     specimen inadequate for diagnosis
     Special tests of biopsy specimen to
     establish the exact type of lymphoma
     • Cell surface markers
     • Genetic studies (if needed)




     Burkitt’s Lymphoma                                 the patient’s general health and whether
     (This section also applies to a type once called   there has been any fever or weight loss.
     Burkitt’s-like lymphoma.)                              Blood tests are done to check the blood
        The diagnosis is made by biopsy of a            counts, liver function, kidney function, and
     lymph node or, sometimes, bone marrow. A           calcium, uric acid, and LDH levels. All these
     pathologist experienced in diagnosing lym-         tests provide information about the patient’s
     phomas should examine these samples. The           general health and how advanced the lym-
     diagnosis should be confirmed by studying          phoma is. A chest x-ray or CT scan of the
     the cell surface markers. Sometimes genetic        chest is done, as well as a bone marrow test if
     studies are useful. A complete medical history     it hasn’t been done already. A CT of the
     and physical examination should be done. The       abdomen and pelvis is also recommended.
     doctor will want to know if lymph nodes, the       Because this lymphoma often involves the
     spleen, or liver is enlarged. The doctor will      central nervous system, a spinal tap should be
     also examine other organ systems, ask about        done to look for lymphoma cells in the spinal
                                                        fluid. HIV testing is also recommended.

62
                                     Burkitt’s Lymphoma


        Evaluation


        Doctor must do:
        • Physical examination with special attention to areas
          with lymph nodes, back of throat, liver, and spleen
        • Check general health and activity
        • Ask about fever and/or weight loss
        • Complete blood count
        • Blood tests of kidney and liver function and LDH,
          calcium, and uric acid levels                                                                              See next
        • Chest x-ray or CT scan                                                                                     page for
        • CT scans of abdomen and pelvis                                                                             initial
                                                                                                                     treatment
        • Bone marrow biopsy
        • Spinal tap to test fluid for lymphoma
        • HIV test

        Useful in some cases:
        • CT scan of the neck
        • Blood test for beta-2-microglobulin
        • Discuss efffect of treatment on fertility




                                                         ©2005 by the National Comprehensive Cancer Network (NCCN) and the
                                                         American Cancer Society (ACS). All rights reserved. The information herein
                                                         may not be reproduced in any form for commercial purposes without the
                                                         expressed written permission of the ACS. Single copies of each page may be
                                                         reproduced for personal and non-commercial uses by the reader.




    A CT of the neck may be helpful if there is          oved or have only a single tumor outside the
suspicion of enlarged lymph nodes in this                abdomen. They can be entered into a clinical
area. A blood test for beta-2-microglobulin              trial or given chemotherapy with combina-
might be useful. Finally, because treatment              tions of drugs such as cyclophosphamide,
may affect fertility, this needs to be discussed         vincristine, doxorubicin and high doses of
if the patient wants to have a family.                   methotrexate or a similar combination that
    Certain patients are considered low risk,            also includes dexamethasone and cytarabine.
meaning they have an excellent chance of cure.           If the lymphoma completely disappears, no
They have a normal blood LDH level and have              further treatment is needed and routine follow-
had a single abdominal tumor completely rem-             up care is recommended. If it doesn’t disappear,

                                                                                                                                      63
                                    Treatment Guidelines for Patients


     How Serious Is                                             Initial Treatment
     the Lymphoma?



                                                                 Clinical trial
     Low risk
                                                                 OR
     • Normal LDH
                                                                 Combination chemotherapy with:
     • Surgery completely
       removes abdominal                                         •   High doses of alkylating agents
       tumor or only tumor                                       •   Anthracycline
       outside abdomen                                           •   Chemotherapy into spinal fluid
                                                                 •   High doses of methotrexate




                                                                 Clinical trial
                                                                 OR
                                                                 Combination chemotherapy with:
     High risk
                                                                 •   High doses of alkylating agents
                                                                 •   Anthracycline
                                                                 •   High doses of methotrexate
                                                                 •   Chemotherapy into spinal fluid




     then entrance into a clinical trial is the best   be added. Chemotherapy is also given into
     next step, or they can receive another chemo-     the spinal fluid.
     therapy regimen chosen by their doctor                If the lymphoma completely disappears
         For patients who are at high risk — high      after treatment, no more treatment may be
     LDH or multiple tumors that can’t be com-         needed and patients can be observed with
     pletely removed — a clinical trial may be most    frequent checkups. Another option is entrance
     appropriate. Other treatment can be combi-        into a clinical trial to test whether more
     nation chemotherapy that includes high doses      treatment is worthwhile. If the lymphoma
     of alkylating agents such as cyclophosphamide     doesn’t go away completely, patients can
     or ifosfamide and anthracyclines such as          receive further treatment in a clinical trial or
     doxorubicin along with methotrexate and           may be treated with a chemotherapy regimen
     cytarabine given in high doses. Rituximab may     chosen by their doctor. They may also decide
64
                      Burkitt’s Lymphoma (continued)


     Response                     Follow-up                                                    Additional
                                                                                               Treatment

                                  Follow-up every 2 months
     Lymphoma                     for 1 year, then every 3                                      Clinical trial
     completely                   months for 1 year, then                                       OR
     disappears                   every 6 months (relapse                                       Supportive care
                                  after 2 years is rare)


                                                                                                Clinical trial
     Lymphoma
                                                                                                OR
     doesn’t
     completely                                                                                 Individual treatment
     disappear                                                                                  agreed on by doctor
                                                                                                and patient

                                  Follow-up every 2 months
                                  for 1 year, then every 3
     Lymphoma                     months for 1 year, then                                       Clinical trial
     completely                   every 6 months                                                OR
     disappears                   OR                                                            Supportive care
                                  Additional treatment as
                                  part of a clinical trial

                                                                                                Clinical trial
     Lymphoma
                                                                                                OR
     doesn’t
     completely                                                                                 Individual treatment
     disappear                                                                                  agreed on by doctor
                                                                                                and patient



                                                    ©2005 by the National Comprehensive Cancer Network (NCCN) and the
                                                    American Cancer Society (ACS). All rights reserved. The information herein
                                                    may not be reproduced in any form for commercial purposes without the
                                                    expressed written permission of the ACS. Single copies of each page may be
                                                    reproduced for personal and non-commercial uses by the reader.




to receive supportive care to relieve their         of the body with breakdown products of the
symptoms. These choices are also suggested          dead lymphoma cells (tumor lysis syndrome).
for patients whose lymphoma comes back              These breakdown products can interfere with
after completely disappearing.                      heart and kidney function. Drugs such as
    The doctor must consider the possibility        allopurinol or rasburicase and large amounts
that the lymphoma might be destroyed quickly        of intravenous fluids containing sodium
by the chemotherapy. This can lead to flooding      bicarbonate can prevent this problem.
                                                                                                                                 65
                                       Treatment Guidelines for Patients


     Diagnosis




     Lymph node biopsy or bone marrow
     biopsy for diagnosis of lymphoma
     Review by pathologist experienced in
     diagnosis of lymphomas.
     Special tests of biopsy specimen to
     establish the exact type of lymphoma
     • Cell surface markers
     • Genetic studies (if needed)




     Lymphoblastic Lymphoma                           will also examine other organ systems, ask
     The diagnosis is made by biopsy of a lymph       about the patient’s general health and whether
     node or, sometimes, bone marrow. A pathol-       there has been any fever or weight loss.
     ogist experienced in diagnosing lymphomas           Blood tests are done to check the blood
     should examine these samples. The diagno-        counts, liver function, kidney function, and
     sis should be confirmed by studying the cell     calcium, uric acid, and LDH levels. All these
     surface markers. Sometimes genetic studies       tests provide information about the patient’s
     are useful. A complete history and physical      general health and how advanced the lym-
     examination should be done. The doctor will      phoma is. A chest x-ray or CT scan of the
     want to know if lymph nodes are enlarged or      chest is done, as well as a bone marrow test if
     if the spleen or liver is enlarged. The doctor   it hasn’t been done already. A CT of the

66
                                Lymphoblastic Lymphoma


      Evaluation




      Doctor must do:
      • Physical examination with special attention to areas with lymph nodes,
        back of throat, liver, and spleen
      • Determine general health and activity level
      • Determine if symptoms of fever and/or weight loss are present
      • Complete blood count
      • Blood tests of kidney and liver function and LDH, calcium, and uric
        acid levels
                                                                                                                Continued
      • Chest x-ray and CT scan
                                                                                                                on next page
      • CT scans of abdomen and pelvis
      • Bone marrow aspiration and biopsy on one or both sides of pelvic bone
      • Spinal tap to test fluid for lymphoma

      Useful to do in some cases:
      • CT or MRI of head
      • Pregnancy test; fertility discussion
      • Blood test for beta-2-microglobulin




                                                         ©2005 by the National Comprehensive Cancer Network (NCCN) and the
                                                         American Cancer Society (ACS). All rights reserved. The information herein
                                                         may not be reproduced in any form for commercial purposes without the
                                                         expressed written permission of the ACS. Single copies of each page may be
                                                         reproduced for personal and non-commercial uses by the reader.




abdomen and pelvis is also recommended.                  brain and a blood test for beta-2-microglobulin
Because this lymphoma often involves the                 might be helpful. Finally, because treatment
central nervous system, a spinal tap should              may affect fertility, this needs to be discussed
be done to look for lymphoma cells in the                if the patient wants to have a family.
spinal fluid. In some patients, an MRI of the

                                                                                                                                      67
                                     Treatment Guidelines for Patients


     Stage                                                    Initial Treatment




                                                               Clinical trial
                                                               OR
                                                               Combination chemotherapy that
     All stages—this lymphoma                                  may include:
     is rarely, if ever, localized                             • High doses of cyclophosphamide
                                                               • Anthracycline
                                                               • Vincristine and asparaginase
                                                               • Chemotherapy into spinal fluid




         The treatment of this type of lymphoma         If the lymphoma completely disappears
     can be given as part of a clinical trial. Or    after treatment, no more treatment may be
     treatment can be combination chemotherapy       needed, and patients can be followed with
     that includes intensive treatment with alky-    frequent checkups. A clinical trial of more
     lating agents such as cyclophosphamide and      treatment may be suggested. If the lymphoma
     anthracyclines such as doxorubicin along with   doesn’t completely disappear, patients can
     vincristine and asparaginase. Chemotherapy      receive further treatment in a clinical trial
     is also given into the spinal fluid.            or may be treated with chemotherapy and

68
                 Lymphoblastic Lymphoma (continued)


     Response               Additional Treatment




                                                                                                Combination
    Lymphoma                 Observation
                                                             If relapse                         chemotherapy
    completely               OR
                                                             occurs                             OR
    disappears               Clinical trial
                                                                                                Clinical trial




    Lymphoma                 Clinical trial
    doesn’t
                             OR
    completely
    disappear                Supportive care




                                                ©2005 by the National Comprehensive Cancer Network (NCCN) and the
                                                American Cancer Society (ACS). All rights reserved. The information herein
                                                may not be reproduced in any form for commercial purposes without the
                                                expressed written permission of the ACS. Single copies of each page may be
                                                reproduced for personal and non-commercial uses by the reader.




supportive care to relieve their symptoms.      to flooding of the body with breakdown
Patients whose lymphoma comes back may          products of the dead lymphoma cells. These
still respond to chemotherapy and another       breakdown products can interfere with heart
course of chemotherapy, or participation in a   and kidney function. Drugs such as allopurinol
clinical trial is suggested.                    or rasburicase and large amounts of intra-
    The doctor must consider the possibility    venous fluids containing sodium bicarbonate
that the lymphoma might be destroyed            can prevent this problem.
quickly by the chemotherapy. This can lead

                                                                                                                             69
                                         Treatment Guidelines for Patients


     Diagnosis




     Lymph node biopsy or bone marrow
     biopsy for diagnosis of lymphoma
     Review by pathologist experienced
     in diagnosis of lymphomas. Repeat
     biopsy if specimen inadequate for
     diagnosis
     Special tests of biopsy specimen to
     establish the exact type of lymphoma
     • Cell surface markers
     • Genetic studies (if needed)




     AIDS-Related B-Cell Lymphoma                      want to know if lymph nodes, spleen, or liver is
     The diagnosis is made by biopsy of a lymph        enlarged. The doctor will also examine other
     node or, sometimes, bone marrow. A pathol-        organ systems and the patient’s general health.
     ogist experienced in diagnosing lymphomas            Blood tests are done to check the blood
     should examine these samples. The diagnosis       counts, liver function, kidney function, and
     should be confirmed by studying the cell sur-     calcium, uric acid, and LDH levels. All these
     face markers. Sometimes genetic studies are       tests provide information about the patient’s
     useful. A complete medical history and physical   general health and how advanced the lym-
     examination should be done. The doctor will       phoma is. A chest x-ray or CT scan of the

70
                           AIDS-Related B-cell Lymphoma


        Evaluation


        Doctor must do:
        • Physical examination with special attention to areas
          with lymph nodes, back of throat, liver, and spleen
        • Check general health and activity
        • Ask about fever and/or weight loss
        • Complete blood count
        • Blood tests of kidney and liver function and LDH,
          calcium, and uric acid levels
        • Chest x-ray or CT scan
        • CT scans of abdomen and pelvis
        • Bone marrow biopsy
                                                                                                                See next page
        • Spinal tap to test fluid for lymphoma
                                                                                                                for initial
        • CD4 cell count                                                                                        treatment
        • Blood test for amount of HIV present

        Useful in some cases:
        • CT scan of the neck
        • CT or MRI of head
        • Upper and lower gastrointestinal x-ray or endoscopy
        • Discuss effect of chemotherapy on fertility
        • Bone x-rays and bone scan
        • Blood test for beta-2-microglobulin
        • Gallium scan or PET scan
        • Stool blood test if anemic



                                                         ©2005 by the National Comprehensive Cancer Network (NCCN) and the
                                                         American Cancer Society (ACS). All rights reserved. The information herein
                                                         may not be reproduced in any form for commercial purposes without the
                                                         expressed written permission of the ACS. Single copies of each page may be
                                                         reproduced for personal and non-commercial uses by the reader.




chest is done, as well as a bone marrow test if          be done to look for lymphoma cells in the
it hasn’t been done already. A CT of the                 spinal fluid. Finally, the number of CD4 lym-
abdomen and pelvis is also suggested.                    phocytes (helper T cells) in the blood (CD4
Because this lymphoma often involves the                 count) should be measured along with the
central nervous system, a spinal tap should              blood level of HIV.

                                                                                                                                      71
                                     Treatment Guidelines for Patients


     Diagnosis


                                                        CD4 cell count is
                                                        over 200
                                                        OR
                                                        There has been no
                                                        anti-HIV therapy
     Burkitt’s lymphoma




                                                        CD4 cell count is
                                                        below 100




     Diffuse large B-cell lymphoma




     Primary lymphoma of the
     brain and/or spinal canal




        Treatment depends on the type of lym-           CD4 count is below 100, patients may enter a
     phoma. If the diagnosis is Burkitt’s lymphoma      clinical trial, or they can receive combination
     and the CD4 count is over 200 or there has         chemotherapy like CHOP. High-dose chemo-
     been no anti-HIV therapy, treatment can be         therapy including methotrexate can be added.
     either a clinical trial or combination chemo-      They should also receive G-CSF. Treatment
     therapy that includes high doses of                for the HIV infection and radiation therapy
     methotrexate or high doses of alkylating           should also be given.
     agents. All patients should receive granulocyte-       If the lymphoma is diffuse large B-cell, then
     colony stimulating factor (G-CSF) to help          patients can be treated as part of a clinical
     keep up their white blood cell counts. If the      trial, or they can receive standard treatment

72
                 AIDS-Related B-cell Lymphoma (continued)


        Initial Treatment

         Clinical trial
         OR
         • Anitretroviral drugs for the HIV infection
         • Treatment with combination chemotherapy as for Burkitt’s that includes
           high doses of methotrexate or cyclophosphamide
         • All patients should receive G-CSF to keep up their white blood cell counts


         Clinical trial
         OR
         • Treatment with combination chemotherapy like CHOP that includes high
           doses of methotrexate or cyclophosphamide
         • All patients should receive G-CSF to keep up their white blood cell counts
         • Antiretroviral drugs for the HIV infection
         • Radiation treatment


         See treatment for diffuse B-cell lymphoma (page 64)
         OR
         •   Clinical trial
         •   Chemotherapy such as EPOH, CDE, or CHOP
         •   Antiretroviral drugs for the HIV infection
         •   All patients should receive G-CSF to keep up their white blood cell counts
         •   Chemotherapy should be given into the spinal fluid


         Clinical trial
         OR
         • Treatment with high doses of methotrexate
         • Radiation treatment alone
         • All patients should receive drugs for the HIV infection


                                                           ©2005 by the National Comprehensive Cancer Network (NCCN) and the
                                                           American Cancer Society (ACS). All rights reserved. The information herein
                                                           may not be reproduced in any form for commercial purposes without the
                                                           expressed written permission of the ACS. Single copies of each page may be
                                                           reproduced for personal and non-commercial uses by the reader.




for this type of lymphoma as outlined earlier.             patients with this type of lymphoma, treatment
The only difference is that they should also               can be radiation to the lymphoma or high
receive anti-HIV treatment and G-CSF.                      doses of methotrexate. Treatment for the HIV
    Another AIDS-related lymphoma is pri-                  infection should also be given.
mary central nervous system lymphoma. For

                                                                                                                                        73
     NOTES




74
                                       Glossary

Abdomen                                            against foreign agents, such as bacteria.
The part of the body between the chest and         These agents contain certain substances
pelvic bones. It contains the stomach, small       called antigens. Each antibody works against
and large intestine, liver, gallbladder, spleen,   a specific antigen.
and pancreas.
                                                   Autologous transplant
Alkylating agents                                  This kind of transplant is mainly used to treat
Specific types of chemotherapy drugs.              lymphomas, although it is sometimes used
Cyclophosphamide and ifosfamide are two            for other cancers. In this type of transplant,
examples.                                          you act as your own donor, using stem cells
                                                   from either your bone marrow or circulating
Allogeneic transplant
                                                   blood. Your stem cells are removed through a
A type of stem cell transplant. The stem cells
                                                   process called “harvesting,” and then frozen.
come not from the patient, but from a donor
                                                   The stem cells will be given back to you after
whose tissue type best matches the patient.
                                                   you have received high doses of chemotherapy,
The donor is most often a family member,
                                                   radiation, or both.
usually a sibling, but if there is not a good
match in the family, one can often be found        Benign
from the general public through a national         Not cancer; not malignant.
registry. One new source of stem cells is blood
                                                   Beta-2-microglobulin
taken from the placenta and umbilical cord
                                                   A protein made by immune cells and lym-
of newborns. This blood contains a relatively
                                                   phoma cells.
high number of stem cells. Still, the numbers
are often too low for adults and this source of    Biopsy
stem cells is used mostly in children.             The removal of a sample of tissue to see
                                                   whether cancer cells are present. There are
Anthracyclines
                                                   several kinds of biopsies. In fine needle aspi-
Specific chemotherapy drugs. Doxorubicin
                                                   ration (FNA) biopsy, a very thin needle is used
(Adriamycin) is one example.
                                                   to draw fluid and cells from a lump. In an
Antibody                                           excisional biopsy, the whole lump or tumor is
A protein produced by immune system cells          removed.
and released into the blood. Antibodies defend



                                                                                                     75
     Bone marrow                                          Contrast agent
     The soft tissue in the hollow of flat bones of       A substance that is injected or swallowed
     the body that produces new blood cells.              before an x-ray examination to help outline
                                                          body structures more clearly.
     CD4 count
     The CD4 is a protein found on the surface of         Cytogenetics
     helper T lymphocytes and some macro-                 This refers to looking at the chromosomes —
     phages. The human immunodeficiency virus             are they normal or abnormal?
     (HIV) attaches to this protein. As the helper
                                                          Cytokine
     T lymphocytes become infected, they die. A
                                                          A product of cells of the immune system that
     CD4 count identifies the number of helper T
                                                          may stimulate immunity and cause the
     lymphocytes circulating in the blood, which
                                                          regression of some cancers.
     is an indication of the body’s immunity.
                                                          Diaphragm
     Cell Surface Markers
                                                          The breathing muscle that aids breathing. It
     Proteins on the surface of lymphoma cells
                                                          separates the chest from the abdomen.
     that help to identify the type of lymphoma.
     For example, in lymphoblastic lymphomas              DNA
     CD10, CD19. and Tdt are present.                     Deoxyribonucleic acid; DNA holds genetic
                                                          information on cell growth, division, and
     Chemotherapy
                                                          function.
     Treatment with drugs to destroy cancer cells.
     Chemotherapy is often used with surgery or           Endoscopy
     radiation to treat cancer when the cancer has        Procedure in which a flexible lighted tube
     spread, when it has come back (recurred), or         (gastroscope, sometimes called an endoscope)
     when there is a strong chance that it could          is placed into the stomach through the throat
     recur.                                               and esophagus (swallowing tube) so that the
                                                          stomach lining can be seen and a biopsy
     Computed tomography
                                                          taken.
     An imaging test in which many x-rays are taken
     from different angles of a part of the body. A       Growth factor
     computer combines these images to produce            A naturally occurring protein that causes
     cross-sectional pictures of internal organs.         cells to grow and divide. Too much growth
     Except for the injection of a dye (needed in         factor production by some cancer cells helps
     some but not all cases), this is a painless proce-   them grow quickly, and new treatments to
     dure that can be done in an outpatient clinic. It    block these growth factors are being tested
     is often referred to as a “CT” or “CAT” scan.        in clinical trials. Other growth factors help
                                                          normal cells recover from side effects of
                                                          chemotherapy.



76
Helicobacter pylori                                Localized cancer
A bacterium that infects the stomach and is        A cancer that is confined to the place where
thought to cause stomach lymphomas and             it started; that is, it has not spread to distant
stomach cancers.                                   parts of the body.
HIV                                                Lymph nodes
Human Immunodeficiency Virus, the virus            Small bean-shaped collections of immune
that causes AIDS.                                  system tissue, such as lymphocytes, found
                                                   along lymphatic vessels. They remove cell
Imaging tests
                                                   waste and fluids from lymph. They help fight
Methods used to produce a picture of internal
                                                   infections and also have a role in fighting
body structures. Some imaging methods
                                                   cancer. Also called lymph glands.
used to help diagnose cancer are x-rays, CT
scans, magnetic resonance imaging (MRI),           Lymphocytes
and ultrasound.                                    A type of white blood cell that helps the body
                                                   fight infection.
Immune system
The complex system by which the body               Lymphoid tissue (lymphatic system)
resists infection by microbes such as bacteria     The tissues and organs (including lymph
or viruses and rejects transplanted tissues or     nodes, spleen, thymus, and bone marrow)
organs. The immune system may also help            that produce and store lymphocytes (cells
the body fight some cancers.                       that fight infection) and the channels that
                                                   carry the lymph fluid. The entire lymphatic
Immunohistochemistry
                                                   system is an important part of the body’s
A laboratory test that uses antibodies to
                                                   immune system. Invasive cancers sometimes
detect specific chemical antigens in cells or
                                                   penetrate the lymphatic vessels (channels)
tissue samples viewed under a microscope.
                                                   and spread (metastasize) to lymph nodes.
This procedure can be used to help detect
and classify cancer cells. It is also one of the   Magnetic resonance imaging (MRI)
methods used for estrogen receptor assays          A method of taking pictures of the inside of
and progesterone receptor assays. See also         the body. Instead of using x-rays, MRI uses a
monoclonal antibodies.                             powerful magnet and transmits radio waves
                                                   through the body; the images appear on a
LDH
                                                   computer screen as well as on film.
Lactate dehydrogenase; an enzyme, or pro-
tein, that will be elevated in the blood when a    Mediastinum
lot of cancer is present or when cancer has        The area between the two lungs. It is the space
invaded the liver.                                 behind the chest bone and in front of the heart.




                                                                                                       77
     Monoclonal antibodies                             Pelvis
     Antibodies manufactured in the laboratory         The part of the body below the abdomen
     and designed to target substances, called         within the confines of the pelvic bones.
     antigens, recognized by the immune system.
                                                       Performance status
     Monoclonal antibodies that have been
                                                       A measure of how active a patient is. Two
     attached to chemotherapy drugs or radioac-
                                                       scales used in the United States are the
     tive substances are being studied for their
                                                       Eastern Cooperative Oncology Group (ECOG)
     potential to seek out antigens unique to
                                                       Performance Scale, which ranks the health of
     cancer cells and deliver these treatments
                                                       people with cancer from 0 (the best) to 4, and
     directly to the cancer, thus killing the cancer
                                                       the Karnofsky scale, which goes from 100 (the
     cell and not harming healthy tissue.
                                                       best) to 0. Performance status is an excellent
     Monoclonal antibodies are also often used in
                                                       predictor of a patient’s outlook and ability to
     immunohistochemistry to help detect and
                                                       tolerate certain kinds of therapy
     classify cancer cells. Other studies are being
     done to see if radioactive atoms attached to      Platelet
     monoclonal antibodies can be used in imag-        A part of the blood that plugs up holes in
     ing tests to detect and locate small groups of    blood vessels after an injury. Chemotherapy
     cancer cells.                                     can cause a drop in the platelet count, a con-
                                                       dition called thrombocytopenia that carries
     MUGA scan
                                                       a risk of excessive bleeding.
     A special scan of the heart that uses a radio-
     active substance that is injected into the        Positron emission tomography (PET)
     blood. It measures how well the heart pumps.      A PET scan creates an image of the body (or
                                                       of biochemical events) after the injection of a
     Nonmyeloablative transplants
                                                       very low dose of a radioactive form of a sub-
     A kind of allogeneic transplant that uses low
                                                       stance such as glucose (sugar). The scan
     doses of chemotherapy and allows the donor
                                                       computes the rate at which the tumor is
     stem cells to take over.
                                                       using the sugar. In general, high-grade
     Pathologist                                       tumors use more sugar, and normal and low-
     A doctor who specializes in diagnosis and         grade tumors use less. PET scans are espe-
     classification of diseases by laboratory tests    cially useful in taking images of the brain,
     such as examination of tissue and cells under     although they are becoming more widely
     a microscope. The pathologist determines          used to find the spread of cancer of the
     whether a tumor is benign or cancerous and,       breast, colon, rectum, ovary, or lung. PET
     if cancerous, the exact cell type and grade.      scans may also be used to see how well the
                                                       tumor is responding to treatment.




78
Prognosis                                             Stem Cells
A prediction of the course of disease; the out-       The blood cells that circulate in our bodies
look for the chances of survival.                     start out as young (immature) cells called stem
                                                      cells. Stem cells mostly live in the bone mar-
Radiation therapy
                                                      row, where they produce blood cells. Since
Treatment with high-energy rays (such as x-
                                                      they can change into different types of blood
rays) to kill or shrink cancer cells. The radiation
                                                      cells the body needs, stem cells are said to be
may come from outside of the body (external
                                                      “pluripotent.” The stem cells that circulate in
radiation) or from radioactive materials
                                                      the bloodstream are called peripheral blood
placed directly in the tumor (internal or
                                                      stem cells or PBSCs. There are fewer of them
implant radiation).
                                                      in the bloodstream than in the bone marrow.
Radioimmunotherapy                                    Stem cells make the 3 main types of blood
Treatment using a radioactive substance               cells: red blood cells (RBCs), white blood cells
linked to a specific antibody that attaches to        (WBCs), and platelets.
a tumor when it is injected into the patient
                                                      Thymus
Spleen                                                A small lymphatic gland in the center-front
An organ with large amounts of lymphatic              part of the chest. It is largest in very young
tissue that filters blood. It lies just below the     children and normally shrinks with aging. It
left rib cage.                                        is responsible for T-cell development.
Staging                                               X-rays
The process of finding out whether cancer             One form of radiation that can be used at low
has spread and, if so, how far. More than one         levels to produce an image of the body on
system is used for staging.                           film or at high levels to destroy cancer cells.




                                                                                                         79
     Current ACS/NCCN Treatment Guidelines
     for Patients
     Advanced Cancer and Palliative Care Treatment Guideline for Patients
     (English and Spanish)
     Bladder Cancer Treatment Guidelines for Patients (English and Spanish)
     Breast Cancer Treatment Guidelines for Patients (English and Spanish)
     Cancer Pain Treatment Guidelines for Patients (English and Spanish)
     Cancer-Related Fatigue and Anemia Treatment Guidelines for Patients
     (English and Spanish)
     Colon and Rectal Cancer Treatment Guidelines for Patients (English and Spanish)
     Distress Treatment Guidelines for Patients with Cancer (English)
     Fever and Neutropenia Treatment Guidelines for Patients with Cancer
     (English and Spanish)
     Lung Cancer Treatment Guidelines for Patients (English and Spanish)
     Melanoma Treatment Guidelines for Patients (English and Spanish)
     Nausea and Vomiting Treatment Guidelines for Patients (English and Spanish)
     Ovarian Cancer Treatment Guidelines for Patients (English and Spanish)
     Prostate Cancer Treatment Guidelines for Patients (English and Spanish)




80
The Non-Hodgkin’s Lymphoma Treatment Guidelines for Patients were developed by a diverse group
of experts and were based on the NCCN clinical practice guidelines. These patient guidelines were
translated, reviewed, and published with help from the following individuals.

Terri Ades, MS, APRN-BC, AOCN          Joan McClure, MS                      Mitchell Smith, MD, PhD
American Cancer Society                National Comprehensive                Fox Chase Cancer Center
                                       Cancer Network
Herman Kattlove, MD                                                          Andrew D, Zelenetz, MD, PhD
American Cancer Society                Shannon Rafine                        Memorial Sloan-Kettering
                                       National Comprehensive                Cancer Center
                                       Cancer Network



The NCCN Non-Hodgkin’s Lymphoma Clinical Practice Guidelines were developed by the following
NCCN Panel Members.

Francis Buadi, MD                      Martha J. Glenn, MD                   Pierluigi Porcu, MD
St. Jude Children’s Research           Huntsman Cancer Institute at the      Arthur G. James Cancer Hospital &
Hospital/University of Tennessee       University of Utah                    Richard J. Solove Research Institute
Cancer Institute University of                                               at The Ohio State University
                                       Jon P. Gockerman, MD
Tennessee Cancer Institute
                                       Duke Comprehensive Cancer Center      Leonard Prosnitz, MD
Fernando Cabanillas, MD                                                      Duke Comprehensive Cancer Center
                                       Leo I. Gordon, MD
The University of Texas
                                       Robert H. Lurie                       Mitchell R. Smith, MD, PhD
M. D. Anderson Cancer Center
                                       Comprehensive Cancer Center           Fox Chase Cancer Center
Michael A. Caligiuri, MD               of Northwestern University
                                                                             Eduardo M. Sotomayor, MD
Arthur G. James Cancer Hospital &
                                       Nancy Lee Harris, MD                  H. Lee Moffitt Cancer Center
Richard J. Solove Research Institute
                                       Dana-Farber/Partners CancerCare       & Research Institute at the
at The Ohio State University
                                                                             University of South Florida
                                       Richard T. Hoppe, MD
Myron S. Czuczman, MD
                                       Stanford Hospital & Clinics           Julie M. Vose, MD
Roswell Park Cancer Institute
                                                                             UNMC Eppley Cancer Center at
                                       Ann S. LaCasce, MD
Lloyd E. Damon, MD                                                           The Nebraska Medical Center
                                       Dana-Farber/Partners CancerCare
UCSF Comprehensive Cancer Center
                                                                             Joachim Yahalom, MD
                                       Kevin T. McDonagh, MD
Luis Fayad, MD                                                               Memorial Sloan-Kettering
                                       University of Michigan
The University of Texas                                                      Cancer Center
                                       Comprehensive Cancer Center
M. D. Anderson Cancer Center
                                                                             Andrew D. Zelenetz, MD, PhD / Chair
                                       Auyporn Nademanee, MD
Ian W. Flinn, MD, PhD                                                        Memorial Sloan-Kettering
                                       City of Hope Cancer Center
The Sidney Kimmel Comprehensive                                              Cancer Center
Cancer Center at Johns Hopkins         Oliver Press, MD, PhD
                                       Fred Hutchinson Cancer Research
Andres Forero, MD
                                       Center/Seattle Cancer Care Alliance
University of Alabama at Birmingham
Comprehensive Cancer Center
©2005, American Cancer Society, Inc.
No.9528.10




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