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 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
2. Lukes and Collins
3. Dorfman
4. Bennet et al.,
5. Lennert
6. WHO
7. Working Formulation
8. REAL
9. WHO

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 year survival
__________________factors ________%______________%______
Low ,
Low intermediate
High intermediate
High ,

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
Low intermediate
High intermediate
High

22. Treatment results of aggressive advanced non-Hodgkin’s lymphomas using different chemotherapy programs
1. First-generation: CHOP
- CR: 50-55%. Long-term survival: %.
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
mBACOD
ProMACE-CytoBOM
MACOP-B
Southwest Oncology Group

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

25. Therapy of aggressive non-Hodgkin’s lymphomas
1. Chemotherapy: CHOP
complete remission: %
permanent cure: %
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: %
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): %
2. Consolidation chemotherapy (DHAP)
- 5-year survival (DFS): %

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 %
2. 10-year survival %
- 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: %
- 3-5 year survival (DFS) %
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”