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Non-Hodgkin抯Lymphoma Powered By Docstoc
					Non-Hodgkin’s Lymphoma

    Shahid Waheed, M.D.
Non-Hodgkin’s Lymphoma
•   Increasing in incidence
•   1973-1989 increased by 60%
•   One of the largest increases of any cancer
•   Multiple reasons
    – Increase in diagnostic tools
    – Access to medical care
    – HIV
• Currently accounts for 4% of all cancers
• Approximately 60,000 new cases in U.S.
• Slightly higher in males
• Most common in children
• Second peak ages are 35-64 years
• Whites are at higher risk than blacks and
• HTLV-1 Human T-cell leukemia virus-1,
  associated T-cell lymphoma/leukemia
  occurs more frequently in Japan and
• Burkitt’s lymphoma more common in
• Middle East lymphoma or alpha-chain
  – Alpha heavy-chain disease is a disorder of
    B-lymphoid cells by diffuse thickening of small
    intestine due to a lymphoplasmacytic infiltrate
    with secretion of incomplete IgA heavy chains
• Follicular lymphomas more common in
  U.S. and Europe but rare in Caribbean,
  Africa, China, Japan and the Middle East
Disease Site
• Malignant lymphomas are a heterogeneous group
  – Usually arise from the lymphoid tissue such as lymph
    nodes, spleen and bone marrow, but may arise from any
  – Most frequent sites of extranodal lymphomas
     •   Stomach
     •   Skin
     •   Oral cavity
     •   Pharynx
     •   Small intestine
     •   CNS

• 5-year survival of non-Hodgkin’s
  lymphoma has increased from 30% to 50%
  – Survival improvements mainly in young adults
    and children

• Several genetic rearrangements play an
  important role in non-Hodgkin’s lymphoma
Environmental Factors
• Increased risk occupations
   –   Pesticide applicators
   –   Grain-flour millers
   –   Meat workers
   –   Wood and forestry workers
   –   Farmers
   –   Painters
   –   Chemists
   –   Printers
   –   Mechanics
   –   Workers in the rubber-plastic-synthetic industry
Environmental Factors

• Chemotherapy and radiation therapy
  patients are at increased risk for
  non-Hodgkins lymphoma plus leukemias
• Several viruses are implicated including:
  – EBV
  – HTVL-1
  – Kaposi’s sarcoma – associated herpes virus,
    also known as human herpes 8 or HHV-8, and
    Hepatitis C virus
• Immunodeficiency patients with congenital
  and acquired states of immunosuppression
  are at an increased risk for non-Hodgkin’s
• Conditions associated with congenital
  immunodeficiency states that are associated
  with increased risk
  –   Ataxia-telangiectasia
  –   Wiskott-Aldrich syndrome
  –   Common variable hypogammalobulinemia
  –   X-linked lymphoproliferative syndrome
  –   Severe combined immunodeficiency
• Conditions associated with acquired immunodeficiency
  states that are associated with increased risk
   – HIV infection
   – Iatrogenic immunosuppression
       • For example, bone marrow and organ transplant recipients
   – Long term survivors of Hodgkin’s disease
   – Collagen vascular and autoimmune disease
       •   Sjogren
       •   Rheumatoid
       •   Felty’s syndrome
       •   SLE
       •   Chronic lymphocytic thyroiditis
       •   Angioimmunoblastic lymphadenopathy
GI Lymphomas
• Increased incidence of GI lymphomas seen
  in patients with celiac sprue and
  inflammatory bowel disease, particularly
  Crohn’s disease
Signs and Symptoms
•   Fever
•   Weight loss    B Symptoms
•   Night sweats
•   Fatigue
•   Weakness
Malignant Lymphomas
• Low grade
• Intermediate
• High grade
Diagnostic Evaluation
• Initial diagnostic evaluation should include:
  – Careful history including paying special
    attention to B symptoms
  – Physical examination including evaluation of
  – Biopsy of the lymphadenopathy, which is more
    easily accessible
  – Chest x-ray/CT scans
Diagnostic Evaluation (con’t)
• Bilateral bone marrow biopsies
• Gallium scan/PET scan
• Bone scans
• Chemistries, CBC, liver functions, basal metabolic
  panel and B2-microglobulin
• HIV serology if the history indicates a HTLV-1
  serology especially if there is a continuous
  involvement of hypercalcemia
• Cytogenetic and molecular analyses of bone
  marrow and peripheral blood if indicated
Diagnostic Evaluation (con’t)
• Examination of the CSF especially with
   – Diffuse aggressive non-Hodgkin’s lymphoma if there is
     epidural, bone marrow, testicular, paranasal sinus or
     nasopharyngeal involvement
   – High-grade lymphoblastic lymphomas and small
     noncleaved cell lymphomas (Burkitt’s and non-
     Burkitt’s type)
   – HIV related lymphomas
   – Primary CNS lymphomas
• Selected patient spinal MRI
• One of the most common classifications used in the
  clinical setting is the Working Formulation for Prognostic
  and Therapeutic Decisions. Historically, proposed in 1982
  and is a modification of the Rappaport classification of
  non-Hodgkin’s lymphoma
• Established a uniform language that is clinically relevant
  and useful in predicting survival and curability.
• Classifications based on two criteria
   – Morphology
   – Biologic aggressiveness (low grade, intermediate and high grade)
Pathology (continued)
• Lymphomas and atypical lymphoproliferative
  disorders not recognized by the Working
  – Mantel cell lymphoma
  – Monocytoid B-cell lymphoma
  – Lymphoma of mucosa-associated lymphoid tissue
  – Anaplastic large-cell lymphoma
  – Mycosis fungoides
Pathology (continued)
• Disorders not recognized by the Working
  Formulation (continued)
   –   Angiocentric lymphoma
   –   T-cell rich B-cell lymphoma
   –   Angiotropic (intravascular) large cell lymphoma
   –   Angio-immunoblastic lymphadenopathy
   –   Divergent or discordant lymphoma
   –   Composite lymphoma
   –   Castleman’s disease
   –   Adult T-cell leukemia/lymphoma
Staging and Prognosis
• Determining the extent of the disease in malignant
  lymphoma patients provides prognostic
  information and helpful in treatment planning.
• Ann Arbor stating system most commonly used:
   – I      One lymph node region
   – IE     One extralymphatic organ or site
   – II     Two or more lymph node regions on the same
            side of the diaphragm
   – III    Lymph node regions on both sides of the
Staging and Prognosis (con’t)
 – III E     One extralymphatic organ or site in
             addition to criteria for stage III
 – III S     Spleen in addition to criteria for
             stage III
 – III SE Spleen and one extralymphatic organ or
             site in addition to criteria for stage III
 – IV        One or more extralymphatic organs
             with or without associated lymph node
             involvement (diffuse or disseminated);
                      involved organs should be designated
   by                        subscript letters (P for lung, H
   for liver and M                    for bone marrow).
Staging and Prognosis (con’t)
• Further Classification
  – Class A patients experience no symptoms
  – Class B patients experience unexplained fever
    of more than 101.5, unexplained drenching
    night sweats, or loss of more than 10% of body
    weight within the previous 6 months
The International Index
• Prognostic international index was
  developed by 16 institutions and
  cooperative groups in the U.S., Europe and
  Canada for aggressive non-Hodgkin’s
  lymphoma treated with doxorubicin-
  containing regimens.
The International Index (con’t)
• Clinical features were independently
  predictive of survival, included:
  – Age (less than 60 vs more than 60 years)
  – LDH (less than 1 vsmore than 1 times normal)
  – Performance status (Eastern Cooperative
    Oncology Group [ECOG] 0-1 vs 2-4)
  – Ann Arbor stage (I-II vs III-IV) and a number
    of extranodal sites (less than 1 vs more than 1
• Many treatments available for
  non-Hodgkin’s lymphoma
  – Most commonly used regimen is CHOP
     • Includes Cyclophosphamide, Doxorubicin, Oncovin,
       and Prednisone
  – Treatment of low-grade lymphomas sometimes
    a watch-and-wait approach as the median
    survival is around 6-10 years
• Stage I and II diseases can be treated with a
  combination of chemo/radiation.
• Stage III and IV patients – for younger
  patients the treatment options are quite
  controversial including chemo, radiation or
  even stem cell transplant.

• Newer agents available are interferon-alpha,
  Rituxan, monoclonal antibody that targets
  CD20 antigen found on the surface of most
  B-cell lymphomas.
• Treatment of intermediate-grade lymphomas Stage
  I and II disease the 5-year relapse-free survival
  rates with radiation therapy alone are 50-60% for
  Stage I and Stage IE disease and 10-40% for Stage
  II and IIE disease.
• Multi-drug chemotherapy together with involved-
  field radiation therapy was produced disease-free
  and overall survival rates significantly superior to
  radiation alone.
• Combined modality approaches have yielded 5-
  year relapse free survival rates of 78-95% for
  Stage I-IE disease and 70-75% for Stage II and IIE
• Stage III and IV disease response rates are
  between 50-55% with a 35% long-term disease-
  free survival.
• CHOP is the most commonly used regimen in the
  setting. There are several other regimens that are
• For high-grade lymphomas the same
  chemotherapy regimens are used and CNS
• In lymphoblastic lymphomas regimens used are
  those traditionally used for acute lymphoblastic
• CNS prophylaxis is required in histology of high-
  grade, small, noncleaved and lymphoblastic and
  special sites of involvement bone marrow, testis,
  paranasal sinus, nasopharyngeal and epidural by
  diffuse aggressive non-Hodgkin’s lymphoma.
• Drugs that can be used are Methotrexate
  (12-15 mg) or cytarabine (Ara-C; 25 mg/m)
  can be used for intrathecal therapy.
• Other options include stem cell transplant.

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