Presentation is loading. Please wait.

Presentation is loading. Please wait.

Disordini linfoproliferativi (II) classificazione linfomi staging system prognosi terapia.

There are copies: 1
Linfomi: diagnosi e classificazione. LINFOADENOPATIA definizione: linfonodi di dimensioni anormali (> 1,0-1,5 cm) linfonodi di consistenza anormale epidemiologia:

Similar presentations


Presentation on theme: "Disordini linfoproliferativi (II) classificazione linfomi staging system prognosi terapia."— Presentation transcript:

1 disordini linfoproliferativi (II) classificazione linfomi staging system prognosi terapia

2 B-Cell Neoplasms I. Precursor B-cell neoplasm: a. Precursor B-lymphoblastic leukemia/lymphoma II. Mature (peripheral) B-cell neoplasms a. B-cell chronic lymphocytic leukemia / small lymphocytic lymphoma b. B-cell prolymphocytic leukemia c. Lymphoplasmacytic lymphoma d. Splenic marginal zone B-cell lymphoma (+/- villous lymphocytes) e. Hairy cell leuekmia f. Plasma cell myeloma/plasmacytoma g. Extranodal marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue type h. Nodal marginal zone lymphoma (+/- monocytoid B-cells) i. Follicle center lymphoma, follicular, j. Mantle cell lymphoma k. Diffuse large cell B-cell lymphoma Mediastinal large B-cell lymphoma Primary effusion lymphoma l. Burkitt's lymphoma/Burkitt's cell leukemia

3 T-Cell and Natural Killer Cell Neoplasms I. Precursor T cell neoplasm: a. Precursor T-lymphoblastic lymphoma/leukemia II. Mature (peripheral) T cell and NK-cell neoplasms a. T cell prolymphocytic leukemia b. T-cell granular lymphocytic leukemia c. Aggressive NK-Cell leukemia d. Adult T cell lymphoma/leukemia (HTLV1+) e. Extranodal NK/T-cell lymphoma, nasal type f. Enteropathy-type T-cell lymphoma g. Hepatosplenic gamma-delta T-cell lymphoma h. Subcutaneous panniculitis-like T-cell lymphoma i. Mycosis fungoides/Sézary's syndrome j. Anaplastic large cell lymphoma, T/null cell, primary cutaneous type k. Peripheral T cell lymphoma, not otherwise characterized l. Angioimmunoblastic T cell lymphoma m. Anaplastic large cell lymphoma, T/null cell, primary systemic type

4 * 1) non-Hodkin lymphomas are a diverse collection of approximately * 40 entities, with different immunopathologic and cytogenetic characteristics * 2) the most frequent entities are the: * - Follicle Centre lymphoma (FCL) * - Diffuse Large Cell lymphoma (DLCL) * 3) B-cell derived are by far more frequent compared to T-cell derived * (90% vs. 10%) NON-HODGKIN LYMPHOMAS:

5 FCL non follicular low grade NHL B-cell DLCL T-cell NHL Other lymphomas 30% 6% 16% 28% 20% INCIDENZA DEI VARI TIPI DI LINFOMA NON-HODGKIN

6 Hodgkin's lymphoma (Hodgkin's Disease) a.Nodular lymphocyte predominance Hodgkin's lymphoma b.Classical Hodgkin's lymphoma Nodular sclerosis Hodgkin's lymphoma Lymphocyte-rich classical Hodgkin's lymphoma Mixed cellularity Hodgkin's lymphoma Lymphocyte depletion Hodgkin's lymphoma

7 Hodgkin's Disease - Classification Type Histologic Features Frequency Prognosis Nodular sclerosis Bands of fibrosis, Most frequent type, Good Lacunar cells more common in womenmost are stage I-II Mixed cellular Composed of many Most frequent Fair different cells in older persons, most are stage III second most frequent overall Lymphocyte predominance Mostly B-cells and few Uncommon Good Reed-Sternberg variant cellsmost are stage I or II Lymphocyte depletion Many Reed-Sternberg Uncommon Poor cells and variantsmost are stage III or IV

8 CARATTERIZZAZIONE RISCHIO PROGNOSTICO: biopsia linfonodale biopsia osteo-midollare tipizzazione immunofenotipica tipizzazione molecolare stadiazione della malattia

9

10

11

12

13 DEFINIZIONE RISCHIO PROGNOSTICO: biopsia linfonodale biopsia osteo-midollare tipizzazione immunofenotipica tipizzazione molecolare stadiazione della malattia fattori di rischio

14 Fattori con valore prognostico sfavorevole indipendente: performance status > 2 LDH > normale siti extranodali 2 stadio III o IV età > 60 anni No. di fattori presenti Tipo di rischio prognostico 0-1 basso (L) 2 intermedio-basso (LI) 3 intermedio-alto (HI) 4-5 alto (H)

15

16

17

18 Overall Survival in DLCL according to risk group defined by Age-Adjusted IPI (PS, stage, LDH) Risk groupScore C R Rate (%) 5-yr survival (%) Low09283 Low-intermediate17869 High-intermediate25746 High34632

19 Age ( 60 vs) Sex (F vs M) Extranodal sites (0-1 vs 2) Serum LDH (normal vs elevated) B symptoms (absent vs present) ESR (less than 30 vs at least 30) IIL prognostic system

20 Federico M et al., Blood 2000, 95: Prognosis of follicular lymphoma: a predictive model based on a retrospective analysis of 987 cases

21 Hodgkin's lymphoma (Hodgkin's Disease) a.Nodular lymphocyte predominance Hodgkin's lymphoma b.Classical Hodgkin's lymphoma Nodular sclerosis Hodgkin's lymphoma Lymphocyte-rich classical Hodgkin's lymphoma Mixed cellularity Hodgkin's lymphoma Lymphocyte depletion Hodgkin's lymphoma

22 Hodgkin's Disease - Classification Type Histologic Features Frequency Prognosis Nodular sclerosis Bands of fibrosis, Most frequent type, Good Lacunar cells more common in womenmost are stage I-II Mixed cellular Composed of many Most frequent Fair different cells in older persons, most are stage III second most frequent overall Lymphocyte predominance Mostly B-cells and few Uncommon Good Reed-Sternberg variant cellsmost are stage I or II Lymphocyte depletion Many Reed-Sternberg Uncommon Poor cells and variantsmost are stage III or IV

23 Prognostic classificationFactor Factors with independent prognostic valuefor survival in lymphomas of both high and low grade histology I P I (New Engl J Med 1993) age >60 performance status serum LDH level Ann Arbor stage extranodal involvement aa I P I (New Engl J Med 1993) Performance status serum LDH level Ann Arbor stage I I L (Blood 2000) Age (>60) Sex (male) ESR ( ) Serum LDH level ( ) Systemic symptoms extranodal involvement

24

25

26

27 13-gene predictor: cured gene-espression signature fatal/refractory gene-espression signature

28 13-gene outcome predictor: IPI-outcome predictor:

29 13-gene predictor: cured gene-espression signature fatal/refractory gene-espression signature

30

31 Overall Survival of advanced-stage DLCL with 3rd generation chemotherapy regimens

32 Overall Survival of FCL patients

33

34 Turin-group experience with the i-HDS scheme Corradini P et al, Blood 1997 Jan 15;89: Tarella C et al, Leukemia 2000 Apr 14:740-7 a high-dose approach aimed to obtain maximal tumor cytoreduction and to exploit the in vivo-purging effect operated by chemotherapy

35 VP-16 2 g/sqm APO x 2 DHAP x 2 G - C S F CTX 7 g/sqm PBPC/BM harvest MITOX + L-PAM + PBPC autograft I-HDS SCHEME FOR HIGH-RISK FCL PATIENTS G - C S F MTX 8 g/sqm DEX 40

36 I-HDS REGIMEN IN FCL: results of the Torino group experience Leukemia 2000, 14: CR RATE OF 79% ACCEPTABLE RATE OF EARLY AND LATE TOXICITIES A PROJECTED EFS AT 9 YEARS OF 62% AND A PROJECTED OS OF 78% years % surviving Event-free survival years % surviving Overall survival

37 Gianni AM et al; NEJM 1997; 336: HDS vs MACOP-B in aggressive B-cell NHL

38 MOUSE CHIMERICAL HUMANIZED HUMAN DEVELOPMENT OF MONOCLONAL ANTIBODIES

39 UNLABELED CHIMERIC ANTIBODY IMMUNOTOXIN RADIOCONJUGATE

40 Meccanismo dazione mAbs effetto diretto signaling apoptosi citossico (tossine o radiomarcati) effetto indiretto complemento ADCC (NK, GN) immunosensibilizzazione

41 Principali anticorpi monoclonali unlabelled ANTIGENNAME INDICAZIONI CD20 CD25 CD52 CD22 STRUTTURA Rituximab Basiliximab Daclizumab Campath 1H Epratuzumab Chimerico umanizzato FCL,MCL,HCL, DLCL Trapianto LLC, Trapianto FCL

42 Radiation-induced cytolysis Effector mechanisms TARGET ANTIGENS: NOT SHED NOT INTERNALIZED ? RADIOIMMUNOCONJUGATE NB. Properties of each immunoconiugate depend on which isotope is chosen

43 hd-CY VP16 + CDDP hd- Ara-C PBSC autografting A P O PBSC harvest G-CSF PBSC harvest G-CSF C-HDS + Rituximab schedule RITUXIMAB

44 C-HDS + Rituximab in high-risk DLCL patients: a multicenter italian study R- HDS historical 82% 46-57% 71 % (3yr.) CROS 32-46% (5yr.)

45 identification of residual disease The role of 67 Ga scanning or FDG-PET in discriminating between active or fibrotic residual masses is well established

46 identification of residual disease The value of molecular biology techniques (PCR) in evaluating the minimal residual disease in patients with Bone Marrow involvement at presentation

47 DFS comparison between PCR-positive and PCR-negative patients

48 IMMUNOTERAPIA NEI DISORDINI LINFOPROLIFERATIVI percentuale di guarigione ancora insufficiente crescita abbastanza lenta markers tumore-specifici o lineage-specifici chemioterapia efficace ma non eradicante monitoraggio della malattia minima residua (MMR) MMR spesso MDR+ immunosensibilita della MMR modelli animali disponibili

49 Bendandi et al., Nat Med 5: , 1999

50 week Id/KLH (0.5 mg mg) GM-CSF (150 µg/sqm) VACCINATION SCHEDULE 15 MM in first remission after HDS and PBPC infusion; Protein-based vaccine

51

52 tumor burden remission threshold time diagnosisrelapse remission phase

53 Early detection of recurrent disease 1. The efficacy of salvage treatment is well known in both high and low-grade lymphomas

54 Early detection of recurrent disease 2. salvage treatments are more effective if the recurrent disease is not extensively spread

55 % III-IV (n=259) I-II (n=153) Years after relapse SURVIVAL by Ann Arbor stage at relapse I. I. L p<0.0001


Download ppt "Disordini linfoproliferativi (II) classificazione linfomi staging system prognosi terapia."

Similar presentations


Ads by Google