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Non-Hodgkin’s lymphomas-definition and epidemiology

Non-Hodgkin’s lymphomas-definition and epidemiology. 1. Definition: malignant disease of the lymphoid system, highly heterogeneous, both histologically and clinically. 2. Epidemiology: - annual incidence: 5-10 new cases per 100 000 persons,

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Non-Hodgkin’s lymphomas-definition and epidemiology

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  1. Non-Hodgkin’s lymphomas-definition and epidemiology 1. Definition: malignant disease of the lymphoid system, highly heterogeneous, both histologically and clinically. 2. Epidemiology: - annual incidence: 5-10 new cases per 100 000 persons, - age distribution: middle-age patients and the elderly, - males are affected more often than females (1.5:1.0).

  2. Non-Hodgkin’s lymphomas-Clinical features 1. Constitutional symptoms (fever, night sweats, weight loss) 2. Lymphadenopathy (cervical, supraclavicular, axillary, inguinal, mediastinal, retroperitoneal, mesenteric, pelvic). 3. Mediastinal adenopathy (T cell lymphoma) 4. Extralymphatic involvement (gastrointestinal, testicular masses, solitary bone lesions, CNS). 5. Unexplained anemia and thrombocytopenia ( bone marrow infiltration).

  3. Histologic classification of non-Hodgkin’s lymphomas 1. Rappaport - 1966 2. Lukes and Collins - 1974 3. Dorfman - 1974 4. Bennet et al., - 1974 5. Lennert - 1974 6. WHO - 1976 7. Working Formulation - 1982 8. REAL - 1994 9. WHO - 1999

  4. Histologic classification of non-Hodgkin’s lymphomas - Working Formulation (WF) 1. Low grade 2. Intermediate grade 3. High grade

  5. Histologic classification of non-Hodgkin’s lymphomas - Working Formulation (WF) Low grade A. - Small lymphocytic cell. B. - Follicular, predominantly small cleaved cell C. - Follicular mixed, small cleaved and large cell.

  6. Histologic classification of non-Hodgkin’s lymphomas - Working Formulation (WF) Intermediate grade D. - Follicular, predominantly large cell. E. - Diffuse small cleaved cell. F. - Diffuse mixed, small and large cell. G. - Diffuse large cell.

  7. Histologic classification of non-Hodgkin’s lymphomas - Working Formulation (WF) High grade H. - Large cell immunoblastic. I. - Lymphoblastic. J. - Small noncleaved cell: Burkitt’s

  8. Non-Hodgkin’s lymphomas /NHL/ - clinical features

  9. For the diagnosis of non-Hodgkin’s lymphomas the histological examination of a lymph node is necessary!

  10. Non-Hodgkin’s lymphomas - histological classification

  11. REAL /Revised European-American Lymphoma/-WHO classification of non-Hodgkin’s lymphomas • Precursor B- or T-cell lymphomas • Peripheral B- or T-cell lymphomas

  12. REAL /Revised European-American Lymphoma/-WHO classification of non-Hodgkin’s lymphomas • Precursor B cell lymphomas - acute lymphoblastic leukemia - lymphoblastic lymphoma

  13. REAL /Revised European-American Lymphoma/-WHO classification of non-Hodgkin’s lymphomas • Peripheral B cell lymphomas - Chronic lymphocytic leukemia/lymphocytic lymphoma - Chronic prolymphocytic leukemia - Immunocytoma/lymphoplasmocytic lymphoma - Mantle cell lumphoma - Marginal zone lymphoma /MALT-type/ - Hairy cell leukemia

  14. REAL /Revised European-American Lymphoma/-WHO classification of non-Hodgkin’s lymphomas • Peripheral B cell lymphomas /continued/ - Follicle center cell lymphoma - Plasma cell myeloma/plasmocytoma - Diffuse large B cell lymphoma - Burkitt’s lymphoma - Splenic marginal zone B cell lymphoma

  15. REAL /Revised European-American Lymphoma/-WHO classification of non-Hodgkin’s lymphomas • Precursor T cell lymphomas - Acute lymphoblastic leukemia -Lymphoblastic lymphoma

  16. REAL /Revised European-American Lymphoma/-WHO classification of non-Hodgkin’s lymphomas • Peripheral T cell lymphomas • T cell chronic lymphocytic leukemia • T cell chronic prolymphocytic leukemia • Large granular lymphocyte leukemia /LGL/ • Mycosis fungoides /Sézary syndrome • Peripheral T cell lymphomas, unspecified

  17. REAL /Revised European-American Lymphoma/-WHO classification of non-Hodgkin’s lymphomas • Peripheral T cell lymphomas/continued/ • Angioimmunoblastic T cell lymphoma • Angiocentric lymphoma • Intestinal T cell lymphoma • Adult T cell lymphoma/leukemia • Anaplastic large cell lymphoma

  18. Very aggressive non-Hodgkin’s lymphomas • B-, T-cell acute lymphoblastic leukemia • B-, T-cell lymphoblastic lymphomas • Burkitt’s lymphoma • Adult T cell lymphoma/leukemia

  19. High risk aggressive non-Hodgkin’s lymphomas 1. Age abowe 60 years. 2. Disease stage III and IV. 3. Extranodal involvement of more than 1 site. 4. Serum LDH concentration >1 x normal. 5. Performance status < 80%.

  20. Treatment results of aggressive non-Hodgkin’s lymphomas according to the risk group Risk group No of risk CR 5-year survival __________________factors ________%______________%______ Low 0,1 87 73 Low intermediate 2 67 50 High intermediate 3 55 43 High 4,5 44 26

  21. Treatment results of patients under age 60 with aggressive non-Hodgkin’s lymphomas according to the risk group Risk group No of risk CR 5-year survival factors________%_______________%_________ Low 0 92 87 Low intermediate 1 78 69 High intermediate 2 57 46 High 3 46 32

  22. Treatment results of aggressive advanced non-Hodgkin’s lymphomas using different chemotherapy programs 1. First-generation: CHOP - CR: 50-55%. Long-term survival: 35-50 %. 2. Second-generation: mBACOD, ProMACO-MOPP - CR: 70-80%. Long-term survival: 50-60%. 3. Third-generation: MACOP-B - CR: 84%. Long-term survival: 75% - CR: 52-57%. Long-term survival: 47-56%

  23. Comparative evaluation of treatment results in aggressive advanced non-Hodgkin’s lymphomas 3-year survival Mortality ___%________________%____ CHOP 41 1 mBACOD 46 5 ProMACE-CytoBOM 46 3 MACOP-B 41 6 Southwest Oncology Group

  24. Treatment results in patients over 60 years with aggressive advanced non-Hodgkin’s lymphomas ______Program_____________________5-year survival % CHOP 45 mBACOD 39 ProMACE-CytoBOM 41 MACOP-B 23

  25. Therapy of aggressive non-Hodgkin’s lymphomas 1. Chemotherapy: CHOP • complete remission: 60-80% • permanent cure: 40-60% • refractory/recurrent disease 30-50%

  26. Recommended treatment of aggressive non-Hodgkin’s lymphomas 1. Low risk patients -CHOP 2. High risk patients - CHOP - ablative therapy and hematopoietuc stem cell transplantation

  27. Treatment results of refractory/ recurrent aggressive non-Hodgkin’s lymphomas 1. Chemotherapy programs: DHAP, IMVP16, MINE, ESHAP 2. Complete remission: 20 - 30% 3. 2-3-year survival: ± 10%

  28. Hematopoietic stem cell transplantation in aggressive non-Hodgkin’s lymphomas - Indications 1. Refractory disease 2. Relapse 3. High risk in CR 4. Lymphoblastic and Burkitt’s lymphomas

  29. Treatment results of aggressive non-Hodgkin’s lymphomas with high risk 1. Ablative therapy and hematopoietic stem cell transplantation - 5 year survival (DFS): 70-90% 2. Consolidation chemotherapy (DHAP) - 5-year survival (DFS): 25-50%

  30. Radiotherapy of aggressive non-Hodgkin’s lymphomas 1. Exclusively in pathologic stage I and IE. 2. No indications for combined therapy.

  31. Results of radiotherapy in pathologic stage I/IE aggressive non-Hodgkin’s lymphomas 1. Complete remission - 90% 2. 10-year survival - 54% - patients under 60 years - 75% 3. Chemotherapy - if one of the following symptoms are present: - bulk of disease (lymph node > 7 cm), - high serum LDH concentration, - localization in gastrointestinal track, testicles

  32. Therapy of very aggressive non-Hodgkin’s lymphomas (lymphoblastic, Burkitt’s lymphomas) 1. Previous results: 2-3 year survival: 15% 2. At present - remission induction treatment as in ALL (High risk), - consolidation: a/ ablative therapy and hematopoietic stem cell transplantation (allogeneic or autologous) - CR: 80-100% - 3-5 year survival (DFS) 50-70% b/ high - dose cytarabine

  33. Age-adjasted prognostic index in aggressive non-Hodgkin’s lymphomas 1. Disease stage (I, II vs. III, IV). 2. Serum LDH concentration (< 1x normal vs >1 x normal). 3. Performance status (80% vs < 80%). “Age-adjasted International Prognostic Index”

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