Non-Hodgkin

1
Non-Hodgkins 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
  (1.51.0).

2
Non-Hodgkins 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-Hodgkins
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-Hodgkins
lymphomas - Working Formulation (WF)

• 1. Low grade
• 2. Intermediate grade
• 3. High grade

5
Histologic classification of non-Hodgkins
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-Hodgkins
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-Hodgkins
lymphomas - Working Formulation (WF)

• High grade
• H. - Large cell immunoblastic.
• I. - Lymphoblastic.
• J. - Small noncleaved cell Burkitts

8
Non-Hodgkins lymphomas /NHL/

• - clinical features

9
For the diagnosis of non-Hodgkins lymphomas the
histological examination of a lymph node is
necessary!
10
Non-Hodgkins lymphomas - histological
classification
11
REAL /Revised European-American Lymphoma/-WHO
classification of non-Hodgkins lymphomas

• Precursor B- or T-cell lymphomas
• Peripheral B- or T-cell lymphomas

12
REAL /Revised European-American Lymphoma/-WHO
classification of non-Hodgkins lymphomas

• Precursor B cell lymphomas
• - acute lymphoblastic leukemia
• - lymphoblastic lymphoma

13
REAL /Revised European-American Lymphoma/-WHO
classification of non-Hodgkins 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-Hodgkins lymphomas

• Peripheral B cell lymphomas /continued/
• - Follicle center cell lymphoma
• - Plasma cell myeloma/plasmocytoma
• - Diffuse large B cell lymphoma
• - Burkitts lymphoma
• - Splenic marginal zone B cell lymphoma

15
REAL /Revised European-American Lymphoma/-WHO
classification of non-Hodgkins lymphomas

• Precursor T cell lymphomas
• - Acute lymphoblastic leukemia
• -Lymphoblastic lymphoma

16
REAL /Revised European-American Lymphoma/-WHO
classification of non-Hodgkins 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-Hodgkins 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-Hodgkins lymphomas

• B-, T-cell acute lymphoblastic leukemia
• B-, T-cell lymphoblastic lymphomas
• Burkitts lymphoma
• Adult T cell lymphoma/leukemia

19
High risk aggressive non-Hodgkins lymphomas

• 1. Age abowe 60 years.
• 2. Disease stage III and IV.
• 3. Extranodal involvement of more than 1 site.
• 4. Serum LDH concentration gt1 x normal.
• 5. Performance status lt 80.

20
Treatment results of aggressive non-Hodgkins
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-Hodgkins 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-Hodgkins 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-Hodgkins 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-Hodgkins lymphomas

• ______Program_____________________5-year survival
  
• CHOP 45
• mBACOD 39
• ProMACE-CytoBOM 41
• MACOP-B 23

25
Therapy of aggressive non-Hodgkins lymphomas

• 1. Chemotherapy CHOP
• complete remission 60-80
• permanent cure 40-60
• refractory/recurrent disease 30-50

26
Recommended treatment of aggressive non-Hodgkins
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-Hodgkins lymphomas

• Chemotherapy programs ESHAP, DHAP, IMVP16, MINE
• Complete remission 20 - 30
• 3. 2-3-year survival 10

28
Hematopoietic stem cell transplantation in
aggressive non-Hodgkins lymphomas - Indications

• 1. Refractory disease
• 2. Relapse
• 3. High risk in CR
• 4. Lymphoblastic and Burkitts lymphomas

29
Treatment results of aggressive non-Hodgkins
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-Hodgkins 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-Hodgkins 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 gt 7 cm),
• - high serum LDH concentration,
• - localization in gastrointestinal track,
  testicles

32
Therapy of very aggressive non-Hodgkins
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-Hodgkins lymphomas

• 1. Disease stage (I, II vs. III, IV).
• 2. Serum LDH concentration (lt 1x normal vs gt1 x
  normal).
• 3. Performance status (?80 vs lt 80).
• Age-adjasted International Prognostic Index