Non-Hodgkin lymphoma

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1 Non-Hodgkin lymphoma

2 Non-Hodgkin s lymphoma Definition: - clonal tumours of mature and immature B cells, T cells or NK cells - highly heterogeneous, both histologically and clinically

3 Non-Hodgkin lymphoma Epidemiology annual incidence: 2-18 new cases per 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

4 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)

5 Clinical Presentation Nontender lymph nodes enlargement cervical, supraclavicular, axillary, inguinal, mediastinal, retroperitoneal, mesenteric, pelvic area Extranodal disease gastrointestinal, testicular masses, solitary bone lesions, CNS Other symptoms fatigue, weakness fever cough, chest pain, shortness of breath, vena cava syndrome abdominal pain, bowel disturbances, ascites neurological symptoms cytopenia, autoimmunologic reaction

6 For the diagnosis of non-hodgkin lymphoma the histological examination of a lymph node is necessary!

7 Non-Hodgkin s lymphomas - histological classification

8 Classification of non-hodgkin s lymphomas 1. Rappaport Lukes and Collins Dorfman Bennet et al., Lennert WHO Working Formulation REAL WHO

9 2016 WHO Lymphoid Neoplasms

10 2016 WHO Lymphoid Neoplasms

11 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

12 Staging Classification Lugano Classification

13 Staging Classification Lugano Classification

14 Staging evaluation for lymphoma (1) pathologic documentation physical examination laboratory evaluation complete blood count, ESR liver function tests renal function tests lactate dehydrogenase monoclonal protein viral tests (HIV, CMB, EBV, HCV, HBV)

15 Staging evaluation for lymphoma (2) chest radiograph ultrasonography CT scan of chest, abdomen and pelvis PET bone marrow aspiration / biopsy endoscopy bone radiographs MRI cell-surface marker phenotypic analysis cytogenetics / gene rearrangement analysis

16 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 - - -/

17 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)

18 Treatment results of aggressive non-hodgkin s lymphomas according to the risk group Risk group No of risk CR 5-year survival factor % % Low Low intermediate High intermediate High

19 Treatment of lymphoma Chemotherapy Immunotherapy Hematopoietic stem cell transplantation autologous allogeneic Radioimmunotherapy Surgery Radiotherapy Antibiotic therapy

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

21 Treatment of lymphoma - chemotherapy Monotherapy Chlorambucil Purin analogs Targeted therapy (ibrutinib, idelalisib) Polichemotherapy COP CHOP +/- rituximab CBV ESHAP DHAP EPOCH CODOX/IVAC ProMACE-cytaBOM

22 Treatment of lymphoma Immunotherapy Monoclonal antibodies Anty-CD20 (Rituximab, Mabthera) Anty-CD30 (Brentuximab, Adcetris) Targeted therapy ibrutinib idelalisib Combination therapy CHOP+Rituximab Radioimmunotherapy Zevalin : antycd20+y-ibritumomab tiuxetan Bexxar: antycd20+ I-tositumomab

23 Follicular lymphoma CVP vs R-CVP (n=321). Marcus R et al. Blood 2005

24 Diffuse large B-cell lymphoma OS in DLBCL > 60 yrs (n=399) CHOP vs CHOP-R. Coiffier et al. NEJM 2002

25 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

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