Non-Hodgkin lymphoma

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Non-Hodgkin lymphoma
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Non-Hodgkins lymphoma

• Definition
• - clonal tumours of mature and immature B cells,
  T
• cells or NK cells
• - highly heterogeneous, both histologically and
  clinically

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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
  (1.51.0)
• mature B-cell neoplasms comprise over 90 of
  lymphomas worldwide
• the incidence of lymphomas is increasing wordwide

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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)

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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

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For the diagnosis of non-Hodgkin lymphoma the
histological examination of a lymph node is
necessary!
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Non-Hodgkins lymphomas - histological
classification
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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 - 2008

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REAL /Revised European-American Lymphoma/-WHO
classification of lymphoma

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

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REAL /Revised European-American Lymphoma/-WHO
classification of lymphoma

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

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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
• - Burkitts lymphoma

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REAL /Revised European-American Lymphoma/-WHO
classification of lymphoma

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

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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

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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 ( gt 1/3 widening of mediastinum,
  gt 10cm max.dimension of nodal mass)
• E. Involvement of a single, localised, extranodal
  site

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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)

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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

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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 - - -/ - - - -
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Non-Hogdkin lymphoma - cytogenetics
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International Prognostic Index (IPI)

• Disease stage (I or II vs III or IV)
• Age (60? vs gt60)
• Serum LDH concentration (lt1 x normal vs gt1 x
  normal)
• ECOG performance status (2lt vs ?2)

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Treatment results of aggressive non-Hodgkins
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
  
  

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Treatment of lymphoma

• Chemotherapy
• Immunotherapy
• Hematopoietic stem cell transplantation
• autologous
• allogeneic
• Radioimmunotherapy
• Surgery
• Radiotherapy
• Antibiotic therapy

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Treatment of lymphoma

• First line treatment
• Treatment of relapse
• Treatment of refractory disease
• Treatment of high-risk patients in CR1
• Supportive treatment

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Treatment of lymphoma - chemotherapy

• Monotherapy
• Chlorambucil
• Purin analogs
• Polichemotherapy
• COP
• CHOP /- rituximab
• CBV
• ESHAP
• DHAP
• EPOCH
• CODOX/IVAC
• ProMACE-cytaBOM

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Treatment of lymphoma

• Immunotherapy
• Monoclonal antibodies
• Anty-CD20 (Rituximab, Mabthera)
• Anty-CD52 (alemtuzumab, Campath)
• Interferons
• Interleukin 2
• Combination therapy
• CHOPRituximab
• Radioimmunotherapy
• Zevalin antyCD20Y-ibritumomab tiuxetan
• Bexxar antyCD20 I-tositumomab

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Follicular lymphoma
CVP vs R-CVP (n321). Marcus R et al. Blood 2005
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Diffuse large B-cell lymphoma
OS in DLBCL gt 60 yrs (n399) CHOP vs CHOP-R.
Coiffier et al. NEJM 2002
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Hematopoietic stem cell transplantation in
non-Hodgkins lymphomas

• 1. Refractory disease
• 2. Relapse
• 3. High risk in CR1
• - T-cell lymphoma
• - primary mediastinal B-cell lymphoma
• - mantle cell lymphoma

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Probability of survival after autologous
transplant for follicular lymphoma, by disease
status, 2000-2008
Chemosensitive (N1,995)
Probability of Survival,
Chemoresistant (N160)
P lt 0.0001
0
2
6
1
3
4
5
Years
Slide 44
SUM10_51.ppt
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Probability of survival after autologous
transplant for diffuse large B-cell lymphoma, by
disease status, 2000-2008
Chemosensitive (N6,203)
Probability of Survival,
Chemoresistant (N447)
P lt 0.0001
0
2
6
1
3
4
5
Years
Slide 46
SUM10_53.ppt