Le Neoplasie Ematologiche: Classificazione e Prognosi

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1 Le Neoplasie Ematologiche: Classificazione e Prognosi Giuseppe Longo Dipartimento di Oncologia, Ematologia e Patologie dell Apparato Respiratorio Azienda Ospedaliero Universitaria Policlinico di Modena Modena 22 Dicembre 2011

2 Malattie ematologiche neoplastiche Linfomi di Hodgkin Linfomi non Hodgkin Leucemie Acute Mieloidi (M0,M1,M2,M3,M4,M5,M6,M7) Linfoidi (L1,L2,L3) Leucemie Croniche Leucemia Linfatica Cronica Leucemia Mieloide Cronica Malattie Mieloproliferative Croniche Policitemia Vera, Mielofibrosi, Idiopatica, Leucemia Mieloide Cronica, Trombocitemia Essenziale Sindromi Mielodisplastiche Anemie refrattarie, Anemia refrattaria con sideroblasti ad anello, Anemia refrattaria con eccesso di Blasti tipo I e tipo II, Leucemia Mielomonocitica Cronica Neoplasia delle plasmacellule Mieloma multiplo Leucemia Plasmacellulare

3 The WHO Classification of Hematological Malignancies Pathology Grand Rounds 2008

4 No, it s not that kind of Who

5 Chronic lymphocytic leukemia/small lymphocytic lymphoma B-cell prolymphocytic leukemia Splenic marginal zone lymphoma Hairy cell leukemia Splenic lymphoma/leukemia, unclassifiable Splenic diffuse red pulp small B-cell lymphoma* Hairy cell leukemia-variant* Lymphoplasmacytic lymphoma Waldenström macroglobulinemia Heavy chain diseases Alpha heavy chain disease Gamma heavy chain disease Mu heavy chain disease Plasma cell myeloma Solitary plasmacytoma of bone Extraosseous plasmacytoma

6 Extranodal marginal zone B-cell lymphoma of mucosaassociated lymphoid tissue (MALT lymphoma) Nodal marginal zone B-cell lymphoma (MZL) Pediatric type nodal MZL Follicular lymphoma Pediatric type follicular lymphoma Primary cutaneous follicle center lymphoma Mantle cell lymphoma Diffuse large B-cell lymphoma (DLBCL), not otherwise specified T cell/histiocyte rich large B-cell lymphoma DLBCL associated with chronic inflammation Epstein-Barr virus (EBV)+ DLBCL of the elderly Lymphomatoid granulomatosis Primary mediastinal (thymic) large B-cell lymphoma Intravascular large B-cell lymphoma

7 Primary cutaneous DLBCL, leg type ALK+ large B-cell lymphoma Plasmablastic lymphoma Primary effusion lymphoma Large B-cell lymphoma arising in HHV8-associated multicentric Castleman disease Burkitt lymphoma B-cell lymphoma, unclassifiable, with features intermediate between diffuse large B-cell lymphoma and Burkitt lymphoma B-cell lymphoma, unclassifiable, with features intermediate between diffuse large B-cell lymphoma and classical Hodgkin lymphoma

8 Survival Chronic Lymphocytic Leukemia

9 Survival Lymphoma

10 Survival Lymphoma

11 Survival Lymphoma

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18 Survival Myeloma

19 Hodgkin Lymphoma Nodular lymphocyte-predominant Hodgkin lymphoma Classical Hodgkin lymphoma Nodular sclerosis classical Hodgkin lymphoma Lymphocyte-rich classical Hodgkin lymphoma Mixed cellularity classical Hodgkin lymphoma Lymphocyte-depleted classical Hodgkin lymphoma

20 Linfoma di Hodgkin

21 T-cell prolymphocytic leukemia T-cell large granular lymphocytic leukemia Chronic lymphoproliferative disorder of NKcells* Aggressive NK cell leukemia Systemic EBV+ T-cell lymphoproliferative disease of childhood (associated with chronic active EBV infection) Hydroa vacciniforme-like lymphoma Adult T-cell leukemia/ lymphoma Extranodal NK/T cell lymphoma, nasal type Enteropathy-associated T-cell lymphoma Hepatosplenic T-cell lymphoma

22 Subcutaneous panniculitis-like T-cell lymphoma Mycosis fungoides Sézary syndrome Primary cutaneous CD30+ T-cell lymphoproliferative disorder Lymphomatoid papulosis Primary cutaneous anaplastic large-cell lymphoma Primary cutaneous aggressive epidermotropic CD8+ cytotoxic T-cell lymphoma* Primary cutaneous gamma-delta T-cell lymphoma Primary cutaneous small/medium CD4+ T-cell lymphoma* Peripheral T-cell lymphoma, not otherwise specified Angioimmunoblastic T-cell lymphoma Anaplastic large cell lymphoma (ALCL), ALK+ Anaplastic large cell lymphoma (ALCL), ALK *

23 So what is it? Classification that includes myeloid, lymphoid, histiocytic and mast cell neoplasms applies the principles of the REAL classification to hematological neoplasms morphology immunophenotype genetic features clinical features

24 WHO classification of myeloid neoplasms Myeloproliferative disease (MPD) Myelodysplastic/Myeloproliferative disease Myelodysplastic disease (MDS) Acute myeloid leukemia (AML) AML w/recurrent cytogenetic translocations AML w/ myelodysplasia-related features Therapy-related AML and MDS AML not otherwise categorized

25 Myeloproliferative Disease clonal stem cell disorder with effective hematopoiesis resulting in elevated peripheral blood cells and hepatosplenomegaly Ph1 + CML polycythemia vera idiopathic myelofibrosis essential thrombocytopenia

26 Juvenile myelomonocytic leukemia (JMML) distinct from adult CML or CMML classified as a MDS/MPD lack Ph1 or BCR/ABL translocation usually <3 years old at diagnosis dysplasia present but not prominent

27 Chronic myelomonocytic leukemia (CMML) some patients with MDS features - normal PMN counts, multilineage dysplasia, no organomegaly, and BM morphology of RAEB with monocytosis some patients with MPD features - neutrophilia, monocytosis, and splenomegaly classified as MDS/MPD

28 Atypical CML (acml) lack Ph1 or BCR/ABL translocation predominantly neutrophil series dysplastic as well as proliferative features often multilineage dysplasia worse prognosis than Ph1 + CML classified as MDS/MPD

29 Refractory cytopenia with multilineage dysplasia (RCMD) RA and RARS (FAB) - dysplasia is largely limited to erythroid lineage MDS with <5% blasts but multilineage dysplasia have worse prognosis and are more likely to die of marrow failure or progress to acute leukemia (like RAEB) Multilineage dysplasia is defined as dysplastic features in the cells of two or more cell lines

30 What blast count should define AML? Recent studies have shown that patients with 20-30% blasts (RAEB-T) have similar prognosis to those who have >30% blasts (AML) WHO - AML is defined as >20% blasts RAEB-T category dropped

31 Cytogenetic/molecular categories of AML specific cytogenetic abnormalities do not correlate precisely with FAB categories these should be recognized as distinct entities include low blast count cases previously categorized as MDS (<20% blasts) currently include four categories

32 Cytogenetic/molecular categories of AML AML with t(8;21)(q22;q22),aml1(cbf α)/eto Acute promyelocytic leukemia (AML with t(15;17)(q22;q11-12) and variants, PML/RAR α) AML with abnormal bone marrow eosinophils (inv(16)(p13q22) or t(16;16)(p13;q11), CBF β/myh11x) AML with 11q23 (MLL) abnormalities

33 Dysplasia and AML multilineage dysplasia associated with poor outcomes dysplasia in two or more cell lines history of prior MDS associated with poor outcomes

34 Prior therapy and AML- Alkylating agents different from de novo AML associated with characteristic cytogenetic alterations 3q-, -5, 5q-, -7, 7q-, +8, +9, 11q-, 12p-, -18, -19, 20q-, +21, t(1;7), t(2;11), and complex karyotypes associated with a worse prognosis

35 Prior therapy and AML- Topoisomerase II inhibitors epipodophyllotoxins and adriamycin associated with secondary leukemias (may be lymphoid) associated with cytogenetic abnormalities of de novo AML 11q23 (MLL), occ. t(8;21), inv(16) or t(15;17)

36 Acute Leukemia Survival

37 Haematological Malignancies Chemotherapy Treatment Monoclonal Antibody TK inhibitors Blood and Marrow Transplantation (Bone Marrow, Cord Blood, PBSC) Autologous Allogeneic Syngeneic (Identical Twin) Related (Full Compatibility, Aploidentical) Unrelated

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41 Late Toxicity Treatment Related Cardiotoxicity Gonadal dysfunction Thyroid dysfunction Neurocognitive effects Immunological Defect Second Cancer

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43 Caso Clinico 1 60 aa maschio da diversi mesi dolori ossei Diagnosi di Mieloma Multiplo stadio IIIA Inizia terapia Thal Dex 4 cicli ogni 28 gg e ac. Zoledronico per 2 anni Mobilizzazione e raccolta Staminali con Ciclofosfamide Autotrapianto di midollo Dopo 5 anni di malattia stabile ripresa della malattia Terapia di seconda linea con lenalidomide (RP per 24 mesi) Ripresa di malattia con crolli vertebrali Terapia con Bortezomib risposta per 12 mesi Nuova Progressione di Malattia Terapia con Bendamustina progressione dopo 6 mesi Progressivo deterioramento delle condizioni generali e morte dopo 3 mesi

44 Uomo LMA alto rischio Caso Clinico 2 Chemioterapia d induzione ricovero per 45 gg. Complicanze infettive. Trapianto allogenico da fratello compatibile, ricovero di 60 gg per complicanze infettive intercorse nel post trapianto GVHD cutanea e polmonare trattata con immunosoppressori Numerosi episodi infettivi intercorrenti Dopo 5 anni dal trapianto persiste GVHD cronica con insufficienza respiratoria