non-hodgkin lymphoma. non-hodgkin’s lymphoma definition: - clonal tumours of mature and immature b...
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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– 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– 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 – 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 - 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 - 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– 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 singleextralymphatic 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. AsymptomaticB. 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)
– pathologic documentation – physical examination– documentation of B symptoms– laboratory evaluation
• 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)
– 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 + + - + + - -
FL +vb - + + + - - -
MCL +m + + - + - - -
PLL +b - + - + - - -
SMZL +m - + - + - - -
HCL +m - + - + - - +
MM - - -/+ - - - + -
Non-Hogdkin lymphoma - cytogenetics
International Prognostic Index (IPI)
1. Disease stage (I or II vs III or IV)2. Age (60 vs >60)3. Serum LDH concentration (<1 x normal vs >1 x normal)4. ECOG performance status (2< vs 2)
Treatment results of aggressive non-Hodgkin’s lymphomas according to the risk group
Risk group No of risk CR 5-year survival
factor % %
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
• Radioimmunotherapy • Surgery• Radiotherapy• Antibiotic therapy
Treatment of lymphoma
• 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– 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 disease2. Relapse3. High risk in CR1 - T-cell lymphoma - primary mediastinal B-cell lymphoma - mantle cell lymphoma
Years
0 2 61 3 4 5
Probability of survival after autologous transplant for follicular lymphoma,
by disease status, 2000-2008
Chemosensitive (N=1,995)
Chemoresistant (N=160)
0
20
40
60
80
100
10
30
50
70
90
0
20
40
60
80
100
10
30
50
70
90
Pro
babili
ty o
f Surv
ival, %
P < 0.0001
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Years
0 2 61 3 4 5
Probability of survival after autologous transplant for diffuse large B-cell lymphoma,
by disease status, 2000-2008
Chemosensitive (N=6,203)
Chemoresistant (N=447)
0
20
40
60
80
100
10
30
50
70
90
0
20
40
60
80
100
10
30
50
70
90
Pro
babili
ty o
f Surv
ival, %
P < 0.0001
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