Non-Hodgkin lymphoma
Non-Hodgkin’s lymphoma
Definition:
- clonal tumours of mature and immature B cells, T
cells or NK cells
- highly heterogeneous, both histologically and clinically
Non-Hodgkin lymphoma
• Epidemiology
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annual incidence: 2-18 new cases per 100 000 persons
4% of new cancers each year
age distribution: middle-age patients and the elderly
males are affected more often than females (1.5:1.0)
mature B-cell neoplasms comprise over 90% of lymphomas
worldwide
– the incidence of lymphomas is increasing wordwide
Non-Hodgkin lymphoma
• Etiology
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Viruses: EBV, HTLV1, HHV8, HIV, HCV
Bacteria: Helicobacter pylori, Campylobacter jejuni
Autoimmune disorders
Primary immunodeficiency (SCID, CVID, XLP, Wiskott-Aldrich)
Secondary immunodeficiency (AIDS, PTLD, chemotherapy)
Environmental exposure (herbicide, pesticide)
Clinical Presentation
• Nontender lymph nodes enlargement
– cervical, supraclavicular, axillary, inguinal, mediastinal,
retroperitoneal, mesenteric, pelvic area
• Extranodal disease
– gastrointestinal, testicular masses, solitary bone lesions, CNS
• Systemic symptoms (B symptoms)
– fever
– night sweats
– unexplained weight loss (10% per 6 months)
• Other symptoms
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fatigue, weakness
cough, chest pain, shortness of breath, vena cava syndrome
abdominal pain, bowel disturbances, ascites
neurological symptoms
cytopenia, autoimmunologic reaction
For the diagnosis of non-Hodgkin
lymphoma the histological examination
of a lymph node is necessary!
Non-Hodgkin’s lymphomas - histological
classification
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
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1966
1974
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1974
1976
1982
1994
1999 - 2008
REAL /Revised European-American Lymphoma/WHO classification of lymphoma
• Precursor B- or T-cell lymphomas
• Peripheral B- or T-cell lymphomas
REAL /Revised European-American Lymphoma/WHO classification of lymphoma
• Precursor B cell lymphomas
- acute lymphoblastic leukemia
- lymphoblastic lymphoma
REAL /Revised European-American Lymphoma/WHO classification of lymphoma
Peripheral B cell lymphomas
• Indolent
- Small lymphocytic lymphoma/CLL
- Lymphoplasmocytic lymphoma/immunocytoma
- Marginal zone lymphoma /MALT-type
- Splenic marginal zone B cell lymphoma
- Follicular lymphoma, grade 1-3
• Aggressive
- Diffuse large B cell lymphoma
- Mantle cell lymphoma
- Burkitt’s lymphoma
REAL /Revised European-American Lymphoma/WHO classification of lymphoma
• Precursor T cell lymphomas
- Acute lymphoblastic leukemia
- Lymphoblastic lymphoma
REAL /Revised European-American Lymphoma/WHO classification of lymphoma
• Peripheral T cell lymphomas
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T cell chronic lymphocytic leukemia
T cell chronic prolymphocytic leukemia
Large granular lymphocyte leukemia /LGL/
Mycosis fungoides /Sézary syndrome
Peripheral T cell lymphomas, unspecified
Angioimmunoblastic T cell lymphoma
Angiocentric lymphoma
Intestinal T cell lymphoma
Adult T cell lymphoma/leukemia
Anaplastic large cell lymphoma
Staging Classification
Ann Arbor
• Stage I:
involvement of single lymph node region or a single
extralymphatic organ or site
• Stage II: involvement of two or more lymph node regions on
same side of diaphragm or localized involvement of
an extralymphatic organ or site
• Stage III: involvement of lymph node regions on both sides of
the diaphragm or localized involvement of an
extralymphatic
• Stage IV: diffuse or disseminated involvement of one or
more extralymphatic organs with or without lymph
nod involvement
A. Asymptomatic
B. Symptomatic (B symptoms)
X. Bulky disease ( > 1/3 widening of mediastinum, > 10cm max.dimension of nodal mass)
E. Involvement of a single, localised, extranodal site
Staging evaluation for lymphoma (1)
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pathologic documentation
physical examination
documentation of B symptoms
laboratory evaluation
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complete blood count, ESR
liver function tests
renal function tests
lactate dehydrogenase
monoclonal protein
viral tests (HIV, CMB, EBV, HCV, HBV)
Staging evaluation for lymphoma (2)
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chest radiograph
ultrasonography
CT scan of chest, abdomen and pelvis
bone marrow aspiration / biopsy
PET
endoscopy
bone radiographs
MRI
cell-surface marker phenotypic analysis
cytogenetics / gene rearrangement analysis
Immunophenotyping in B-lymphomas
Type/Ag
SIg
CD5
CD20
CD10
CD19
CD23
CD38
CD103
CLL
+dim
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+
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FL
+vb
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+
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MCL
+m
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+
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+
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PLL
+b
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SMZL
+m
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+
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HCL
+m
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+
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+
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MM
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-/+
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+
-
Non-Hogdkin lymphoma - cytogenetics
International Prognostic Index (IPI)
1.
2.
3.
4.
Disease stage (I or II vs III or IV)
Age (60 vs >60)
Serum LDH concentration (<1 x normal vs >1 x normal)
ECOG performance status (2< vs 2)
Treatment results of aggressive non-Hodgkin’s
lymphomas according to the risk group
Risk group
No of risk
factor
CR
%
5-year survival
%
Low
0-1
87
73
Low intermediate
2
67
50
High intermediate
3
55
43
High
4-5
44
26
Treatment of lymphoma
• Chemotherapy
• Immunotherapy
• Hematopoietic stem cell transplantation
– autologous
– allogeneic
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Radioimmunotherapy
Surgery
Radiotherapy
Antibiotic therapy
Treatment of lymphoma
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First line treatment
Treatment of relapse
Treatment of refractory disease
Treatment of high-risk patients in CR1
Supportive treatment
Treatment of lymphoma - chemotherapy
• Monotherapy
– Chlorambucil
– Purin analogs
• Polichemotherapy
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COP
CHOP +/- rituximab
CBV
ESHAP
DHAP
EPOCH
CODOX/IVAC
ProMACE-cytaBOM
Treatment of lymphoma
• Immunotherapy
– Monoclonal antibodies
• Anty-CD20 (Rituximab, Mabthera)
• Anty-CD52 (alemtuzumab, Campath)
– Interferons
– Interleukin 2
• Combination therapy
– CHOP+Rituximab
• Radioimmunotherapy
– Zevalin : antyCD20+Y-ibritumomab tiuxetan
– Bexxar: antyCD20+ I-tositumomab
Follicular lymphoma
CVP vs R-CVP (n=321). Marcus R et al. Blood 2005
Diffuse large B-cell lymphoma
OS in DLBCL > 60 yrs (n=399) CHOP vs CHOP-R. Coiffier et al. NEJM 2002
Hematopoietic stem cell transplantation in
non-Hodgkin’s lymphomas
1. Refractory disease
2. Relapse
3. High risk in CR1
- T-cell lymphoma
- primary mediastinal B-cell lymphoma
- mantle cell lymphoma
Probability of survival after autologous transplant for
follicular lymphoma,
by disease status, 2000-2008
Probability of Survival, %
100
100
90
90
80
80
Chemosensitive (N=1,995)
70
70
60
60
50
50
Chemoresistant (N=160)
40
40
30
30
20
20
10
10
P < 0.0001
0
0
0
1
2
3
Years
4
5
6
Slide 44
SUM10_51.ppt
Probability of survival after
autologous transplant for diffuse large B-cell lymphoma,
by disease status, 2000-2008
Probability of Survival, %
100
100
90
90
80
80
70
70
Chemosensitive (N=6,203)
60
60
50
50
40
40
30
30
Chemoresistant (N=447)
20
20
10
10
P < 0.0001
0
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0
1
2
3
Years
4
5
6
Slide 46
SUM10_53.ppt