Transcript Non-Hodgkin’s lymphomas-definition and epidemiology 1. Definition: malignant disease of the lymphoid system, highly heterogeneous, both histologically and clinically. 2.

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).
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).
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
-
1966
1974
1974
1974
1974
1976
1982
1994
1999
Histologic classification of non-Hodgkin’s
lymphomas - Working Formulation (WF)
1. Low grade
2. Intermediate grade
3. High grade
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.
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.
Histologic classification of non-Hodgkin’s
lymphomas - Working Formulation (WF)
High grade
H. - Large cell immunoblastic.
I. - Lymphoblastic.
J. - Small noncleaved cell: Burkitt’s
Non-Hodgkin’s lymphomas /NHL/
- clinical features
For the diagnosis of non-Hodgkin’s
lymphomas the histological
examination of a lymph node is
necessary!
Non-Hodgkin’s lymphomas - histological
classification
REAL /Revised European-American
Lymphoma/-WHO classification of
non-Hodgkin’s lymphomas
• Precursor B- or T-cell lymphomas
• Peripheral B- or T-cell lymphomas
REAL /Revised European-American
Lymphoma/-WHO classification of
non-Hodgkin’s lymphomas
• Precursor B cell lymphomas
- acute lymphoblastic leukemia
- lymphoblastic lymphoma
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
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
REAL /Revised European-American
Lymphoma/-WHO classification of
non-Hodgkin’s lymphomas
• Precursor T cell lymphomas
- Acute lymphoblastic leukemia
-Lymphoblastic lymphoma
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
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
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
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%.
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
Treatment results of patients under age 60 with
aggressive non-Hodgkin’s lymphomas
according to the risk group
Risk group
Low
No of risk
CR
5-year survival
factors________%_______________%_________
0
92
87
Low intermediate
1
78
69
High intermediate
2
57
46
High
3
46
32
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%
Comparative evaluation of treatment results in
aggressive advanced non-Hodgkin’s lymphomas
3-year survival
Mortality
___%________________%____
CHOP
mBACOD
ProMACE-CytoBOM
MACOP-B
41
46
46
41
1
5
3
6
Southwest Oncology Group
Treatment results in patients over 60 years with
aggressive advanced non-Hodgkin’s lymphomas
______Program_____________________5-year survival %
CHOP
mBACOD
ProMACE-CytoBOM
MACOP-B
45
39
41
23
Therapy of aggressive non-Hodgkin’s
lymphomas
1. Chemotherapy: CHOP
– complete remission:
– permanent cure:
– refractory/recurrent disease
60-80%
40-60%
30-50%
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
Treatment results of refractory/ recurrent
aggressive non-Hodgkin’s lymphomas
1. Chemotherapy programs: ESHAP, DHAP, IMVP16,
MINE
2. Complete remission:
20 - 30%
3. 2-3-year survival:
± 10%
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
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%
Radiotherapy of aggressive non-Hodgkin’s
lymphomas
1. Exclusively in pathologic stage I and IE.
2. No indications for combined therapy.
Results of radiotherapy in pathologic stage
I/IE aggressive non-Hodgkin’s lymphomas
1. Complete remission
2. 10-year survival
- patients under 60 years
-
90%
54%
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
Therapy of very aggressive non-Hodgkin’s
lymphomas
1. Previous results:
2. At present
2-3 year survival:
15%
- 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
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”