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Non-Hodgkin's Lymphoma

Histopathology

Accurate characterization is critical in assessing prognosis and in planning appropriate management

Immunophenotyping is a useful adjunct to morphologic description of limfoma

NCI modification of Working Formulation is clinically useful classification schema

NCI Clinical Schema for malignant

Indolent

Small lymphocytic

Follicular small cleaved cell

Follicular mixed

Diffuse small cleaved cell

Diffuse intermediate

Aggressive

Follicular, large cell

Diffuse mixed

Diffuse large cell

Diffuse immunoblastic

Highly aggressive (leukemia-like)

Diffuse, small noncleaved cell (Burkitt's and non-Burkitt's)

Lymphoblastic

Adult T-cell leukemia

B. Staging Evaluation limfoma, limphoma

1. History and physical

2. CBC and inspection of smear; LDH

3. CT scanning of torso

4. Gallium scan in aggressive subtypes

5. GI series if symptoms, mass, or blood in stool

6. Bone marrow biopsy

7. Laparotomy is rarely indicated--localized gastric is an exception

C. Indolent ("Favorable")

1. Clinical characteristics

a. Middle-aged (45-60)

b. Usually disseminated at diagnosis but generally confined to nodes, spleen, marrow, and liver

c. Long natural history (median survival 5-7 years)

d. Therapy achieves complete remission in 45-80%

e. Continuous tendency to relapse over time

f. Approximately 40% will transform to a higher grade histology

2. Review of therapeutic approaches

a. Single oral alkylating agent will produce complete remission (CR) in 50% but slowly

b. Combination chemotherapy, e.g. cytoxan, vincristine, and prednisone, produces comparable or slightly higher CR rate but no improvement in relapse-free or overall survival

c. Addition of other drugs to CVP and/or use of total nodal radiation therapy has not clearly improved the outlook

d. Maintenance therapy after CR with chemotherapy doesn't extendoverall survival; unknown role of alpha interferon

e. No initial therapy

i. Asymptomatic stage III-IV patients followed without initial therapy

ii. Median overall survival 11 years

iii. Median time to require therapy 36 months

iv. Spontaneous regression observed in 20%

3. The major question: Are indolent curable?

a. Intensive standard therapies have failed to accomplish this

b. Role of high dose Cytoxan plus total body irradiation and bone marrow transplantation, with or without purged marrow, to be established

c. Contribution of newer agents (Fludarabine, 2-CDA) and immunotherapy