NCCN Non Hodgkins Lymphoma Treatment Guidelines.pdf
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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
1.800.ACS.2345 1.888.909.NCCN
www.cancer.org www.nccn.org
