1. Non-Hodgkin’s Lymphoma Thomas Kochuparambil 10/20/10

2. Non-Hodgkin’s Lymphoma
6th most common cause of cancer death in United States.
Increasing in incidence and mortality.
Since 1970, the incidence of lymphoma has almost doubled.

3. Types of Lymphoma Indolent (low grade) Intermediate
Life expectancy in years, untreated
85-90% present in Stage III or IV
Incurable
Intermediate
Aggressive (high grade)
Life expectancy in weeks, untreated
Potentially curable

4. Classification Rappaport Classification
Kiel and Lukes & Collins Classification
Working Formulation
REAL
WHO Classification 

5. WHO- B Cell
Precursor B-cell neoplasm Precursor B-lymphoblastic leukemia/lymphoma Mature (peripheral) B-cell neoplasms B-cell chronic lymphocytic leukemia / small lymphocytic lymphoma B-cell prolymphocytic leukemia Lymphoplasmacytic lymphoma Splenic marginal zone B-cell lymphoma (+/- villous lymphocytes) Hairy cell leuekmia Plasma cell myeloma/plasmacytoma Extranodal marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue type Nodal marginal zone lymphoma (+/- monocytoid B-cells) Follicle center lymphoma, follicular, Mantle cell lymphoma Diffuse large cell B-cell lymphoma • Mediastinal large B-cell lymphoma • Primary effusion lymphoma Burkitt's lymphoma/Burkitt's cell leukemia

6. WHO-T Cell Precursor T cell neoplasm:
Precursor T-lymphoblastic lymphoma/leukemia
Anaplastic large cell lymphoma, T/null cell, primary systemic type
 Mature (peripheral) T cell and NK-cell neoplasms
T cell prolymphocytic leukemia
T-cell granular lymphocytic leukemia
Aggressive NK-Cell leukemia
Adult T cell lymphoma/leukemia (HTLV1+)
Extranodal NK/T-cell lymphoma, nasal type
Enteropathy-type T-cell lymphoma
Hepatosplenic gamma-delta T-cell lymphoma
Subcutaneous panniculitis-like T-cell lymphoma
Mycosis fungoides/Sézary's syndrome
Anaplastic large cell lymphoma, T/null cell, primary cutaneous type
Peripheral T cell lymphoma, not otherwise characterized
Angioimmunoblastic T cell lymphoma

7. Etiology of NHL Immune suppression DNA repair defects
congenital (Wiskott-Aldrich)
organ transplant (cyclosporine)
AIDS
increasing age
DNA repair defects
ataxia telangiectasia
xeroderma pigmentosum

8. Etiology of NHL Chronic inflammation and antigenic stimulation
Helicobacter pylori inflammation, stomach
Chlamydia psittaci inflammation, ocular adnexal tissues
Sjögren’s syndrome
Viral causes
EBV and Burkitt’s lymphoma
HTLV-I and T cell leukemia-lymphoma
HTLV-V and cutaneous T cell lymphoma
Hepatitis C

9. Clinical Features Lymphadenopathy Cytopenias Systemic symptoms
Hepatosplenomegaly
Fever
Night sweats

10. Clinical Features
Lymphadenopathy may fluctuate or spontaneously remit, especially in low-grade lymphomas.
B symptoms more common in high-grade lymphomas.
Hematogenous spread of disease, with no predictable pattern.

11. Epidemiology
Indolent lymphomas are rare in young people and increase in incidence with age.
Large cell lymphoma is less age related, and is among most common cancers affecting the young.
Burkitt’s and lymphoblastic lymphoma are common in adolescents.
AIDS patients develop aggressive, high grade lymphomas.

12. Clinical Features
Classic lymphoma: arises in lymph node or bone marrow.
Extranodal primary more common in high-grade lymphoma.
Waldeyer’s ring involvement frequent in GI lymphomas.

13. Staging Workup CBC, chemistries, urinalysis
CT scans of chest, abdomen and pelvis
Bone marrow biopsy and aspirate
(Lumbar puncture)
AIDS lymphoma
T cell lymphoblastic lymphoma
High grade lymphoma with positive marrow

14. Diagnosis of NHL Chromosome changes
14;18 translocation in follicular lymphoma
bcl-2 oncogene
t(8;14), t(2;8), t(8;22) in Burkitt’s lymphoma
c-myc oncogene
t(11;14) in mantle cell lymphoma
cyclin D1 gene

15. Staging Workup CBC, chemistries, urinalysis
CT scans of chest, abdomen and pelvis
Bone marrow biopsy and aspirate
(Lumbar puncture)
AIDS lymphoma
T cell lymphoblastic lymphoma
High grade lymphoma with positive marrow

16. Diagnosis of NHL
Excisional biopsy is preferred to show nodal architecture (follicular vs diffuse).
Immunohistochemistry to confirm cells are lymphoid
LCA (leukocyte common antigen)
Monoclonal staining with Igk or Igl
Flow cytometry:
CD 19, CD20 for B cell lymphomas
CD 3, CD 4, CD8 for T cell lymphomas

17. Staging: Ann Arbor I. 1 lymph node region or structure
II. >1 lymph node region or structure, same side of diaphragm
III. Both sides of diaphragm
IV. Extranodal sites beyond “E” designation
subscripts: A, B, E, S

18. Treatment Options: Indolent lymphomas
Diffuse well-differentiated lymphocytic,
Nodular poorly differentiated lymphocytic
10-15% in Stage I or II
potentially curable
local radiotherapy
85-90% Stage III or IV
incurable
treatment does not prolong survival

19. Reasons to Treat in Advanced Indolent Lymphomas
Constitutional symptoms
Anatomic obstruction
Organ dysfunction
Cosmetic considerations
Painful lymph nodes
Cytopenias

20. Treatment Options in Advanced Indolent Lymphomas
Observation only.
Radiotherapy to site of problem.
Systemic chemotherapy
oral agents: chlorambucil and prednisone
IV agents: CHOP, COP, fludarabine, 2-CDA.
Antibody against CD20: Rituxan, Bexxar, Zevalin.
Stem cell or bone marrow transplant.

21. CHOP Chemotherapy Cyclophosphamide (Cytoxan)
Hydroxydaunorubicin (Adriamycin)
Oncovin (vincristine)
Prednisone

22. Treatment Options: Aggressive Lymphomas
Diffuse large cell lymphoma, large cell anaplastic lymphoma, peripheral T cell lymphoma.
Very Aggressive
Burkitt’s lymphoma and lymphoblastic lymphoma.

23. Treatment Options for Early Stage Aggressive Lymphomas
Often in Stage I or II
potentially curable
disseminates through bloodstream early
must use systemic chemotherapy
CHOP x 6 cycles
CHOP x 3 cycles followed by radiotherapy

24. Treatment Options for Advanced Stage Aggressive Lymphomas
Systemic chemotherapy
CHOP (± Rituxan for over 70 age group)
± Intrathecal chemotherapy
AIDS patients and CNS involvement
± Radiotherapy
Spinal cord compression, bulky disease

25. R-CHOP French group ‘GELA’ Randomized trial 399 pts
Elderly (higher risk pts)
CHOP x 8 +/- Rituximab
Improved results with addition of ‘Rituxaimab’
RR 63% 75%
2yr EFS 38%57%
2 yr OS 57%70%
(Coiffier B; N Eng J Med 2002:346:235)

26. Lymphoblastic Lymphoma
T cell malignancy.
Male adolescents.
Mediastinal mass.
T cell variant of T cell acute lymphoblastic leukemia.
Prognosis improving with intensive ALL regimens.

27. Burkitt’s Lymphoma
African variety: jaw tumor, strongly linked to Epstein-Barr Virus infection.
In U.S., about 50% EBV infection.
May present as abdominal mass.
Most rapidly growing human tumor.
Typical chromosome abnormality: c-myc oncogene linked to one of the immunoglobulin genes.

28. Treatment CHOP alone is not sufficient CAL GB 9251 CODOX M EPOCH
HYPER CVAD with alternating Mx + R
Tumorlysis Syndrome
-Resburicase:  recombinant version of a urate oxidase enzyme 

29. Mycosis Fungoides Malignancy of helper T cells. Affinity for skin.
Can be treated with electron beam radiation, ultraviolet light, or topical alkylating agents.

30. Adult T Cell Leukemia-Lymphoma
Associated with HTLV-I infection.
Caribbean, southeastern U.S.
Hepatosplenomegaly, leukocytosis, lymphadenopathy, skin involvement, lytic lesions of bone, hypercalcemia.
May respond to AZT and interferon.

31. AIDS Lymphoma Aggressive lymphomas of B cell origin.
Burkitt’s, Burkitt’s-like, and large cell immunoblastic.
Treatment often limited by immune compromise of the patient.
Prognosis improved with HAART therapy.

32. MALT Lymphoma Mucosa-Associated Lymphoid Tissue
Chronic infection of the stomach by Helicobacter pylori.
Localized to the stomach, indolent course.
Can be cured in many cases by antibiotics against H. pylori.

33. THANK YOU !