GRADO INTERMEDIO Dfollicolare, prevalenza di grandi cellule Ediffuso, a piccole cellule clivate...

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GRADO INTERMEDIO Dfollicolare, prevalenza di grandi cellule Ediffuso, a piccole cellule clivate Fdiffuso, misto a piccole e grandi cellule Gdiffuso a grandi cellule ALTO GRADO Himmunoblastico Ilinfoblastico J piccole cellule non clivate (burkitt) BASSO GRADO Apiccoli linfociti Bfollicolare, prevalentemenete a piccole cellule clivate C follicolare misto, piccole cellule clivate e grandi cellule Slide 2 B-Cell Lymphoma Precursor B-lymphoblastic Small lymphocytic (CLL) Lymphoplasmacytic Mantle cell Follicle center, follicular Grade 1* Grade 2* Grade 3* Follicle center diffuse, small cell Marginal zone B-cell, MALT type Marginal zone B-cell, nodal Marginal zone B-cell, splenic Hairy cell leukemia Plasmacytoma Diffuse large B-cell Diffuse mediastinal large B-cell Burkitts High grade B-cell, Burkitt-like Unclassifiable low grade Unclassifiable high grade Table 1. International Lymphoma Study Group Classification T/NK-Cell Lymphoma Precursor T-lymphoblastic T-cell chronic lymphocytic leukemia Large granular lymphocyte leukemia Mycosis fungoides Peripheral T cell, unspecified Medium-sized Mixed medium and large cell Large cell Lymphoepithelioid Hepatosplenic Subcutaneous panniculitic Angioimmunoblastic Angiocentric, nasal Intestinal Adult T-cell lymphoma/leukemia Anaplastic large cell (including null phenotype) Anaplastic large cell, Hodgkins-like Unclassifiable low grade Unclassifiable high grade Blood, Vol 89, No 11 (June 1), 1997: pp 3909-3918 Slide 3 International Prognostic Index (I.P.I.) Fattoreassentepresente stadioI-IIIII-IV LDHnormalielevate performance status0-12 o > Categoria - rischio RC OS 5 anni basso092%83% int. basso178%69% int. alto257%46% alto346%32% Shipp et al., NEJM 329, 387-394. 1993 Slide 4 OS and IPI Age adjusted index, patients < 69 (n = 1274) Shipp N Engl J Med 329, 987, 1993 28-2-99 SONO TROPPPO BASSE Slide 5 OS and IPI Age adjusted index, patients < 69 (n = 1274) Shipp N Engl J Med 329, 987, 1993 28-2-99 SONO TROPPPO BASSE Slide 6 Slide 7 Slide 8 Fisher Slide 9 EFS Fisher RI, et al. New Engl J Med 328, 1002, 1993 Slide 10 Overall survival Fisher RI, et al. New Engl J Med 328, 1002, 1993 Slide 11 Slide 12 Slide 13 Slide 14 Dipartimento di Scienze Mediche, Oncologiche e Radiologiche - Universit di Modena - Marzo 1998 Slide 15 Slide 16 Slide 17 Slide 18 Gianni Slide 19 Slide 20 Slide 21 Slide 22 Slide 23 Slide 24 Slide 25 Slide 26 Slide 27 De vita, NEJM review Hodgkin Slide 28 Philip Slide 29 Philip T. et al. New Engl J Med 333, 1540, 1995 Slide 30 Slide 31 Haioun Slide 32 Survival benefit of High-Dose Therapy in Poor-Risk Aggressive Non-Hodgkins Lymphoma: Final Analysis of the Prospective LNH87-2 Protocol A Groupe dEtude des Lymphomes de lAdulte Study Haioun C, Lepage E, Gisselbrecht C et al. J Clin Oncol 18, 3025, 2000 Slide 33 LNH87-2median follow-up of 8 yearsfinal analysis: randomized study - consolidative sequential CHT (ifosfamide, etoposide, asparaginase, and cytarabine) vs - HDT using cyclophosphamide, carmustine, and etoposide (CBV regimen) followed by stem-ceIl transplantation Haioun C., et al. J Clin Oncol 18, 3025, 2000 Slide 34 in patients with aggressive NHL in first complete remission after induction higk/intermediate and high-risk patients identified by the age-ad justed internationai prognostic index. Haioun C., et al. J Clin Oncol 18, 3025, 2000 Slide 35 916 eligible patients 451 with two or three risk factors. 277 (61%) reached complete remission 236 randomized 125 patients HDT 111 sequential CHT Haioun C., et al. J Clin Oncol 18, 3025, 2000 Slide 36 8 year OS ABMT64% (95% CI 55%-73%) CHT49% (95% CI 39%-59%) Slide 37 Haioun C., et al. J Clin Oncol 18, 3025, 2000 ABMT 8 year DFS ABMT55% (95% CI 46%-64%) CHT39% (95% CI 30%-48%) CHT Slide 38 Conclusion: On the basis of the final analysis of this prospectively treated series of patients, retrospectively analyzed on the basis of the International Prognostic Index, we hypotesize that HDT benefits patients at higher risk who achieve complete remission after induction treatment Haioun C., et al. J Clin Oncol 18, 3025, 2000 Slide 39 T - cell Slide 40 Peripheral T-CeII Lymphoma - - JAMES O. ARMITAGE: MD, JOHN P GREER. MD.t ALEXANDRA M. LEViNE. MDDENNIS D. WEISENBURGER. MD. SILVIA C. FORMENTI, MD.* MAWT1N BAST. BS, SUE CONLEY, BA. JENE PIERSON. BS, JAMES UNDER. MD, JOHN B. COUSAR. MD AND BHARAT N. NATHWANI, MD Cancer 63:158-163, 1989. Clinical data were reviewed from 134 cases of peripheral T-cell lymphoma diagnosed in three centers. The median age of the patients was 57 years (range, 4-97 yasrs), 59% were male, and 36 patients (27%) had a history of a preceeding disorder of the immune system. The tumors were grooped histologically into large cell (43%), mixed large and small cell (40%), sud small cell (17%). The stage at diagnosis was I(7%), II (21%), III (22%), and IV (50%). B symptoms were present in 57%. The most frequent sites of extranodal involvement were bone marrow (35%), skin (13%), and lung (11%). Eighty patients were treated with a multiagent chemotherapy regimen with proven curative potential in aggressive non-Hodgkins lymphomas and the remainder of the patients received less intensive chemotherapy (36 patients), radiotherapy (9 patients), or no treatment (9 patients). Fifty percent of the Intensively treated patients achieved complete remission and the actuarial 4-years survival was 45%. However, the 4-year disease free survival in patients with Stage IV disease was only 10%. Although peripheral T-cell lymphomas appeared similar in many ways to their B-cell counterpart, disease-free survival by stage was low and patients with Stage IV disease had an especially poor outlook. Slide 41 Armitage, Cancer 63:158-163, 1989. Slide 42 Table 3. Distribution of NHL Cases by the Consensus Diagnosis % Diffuse large B-cell 422 30.6 Follicular304 22.1 Marginal zone B-cell, MALT 1057.6 Peripheral T-cell 96 7.0 Small B-lymphocytic (CLL)93 6.7 Mantle cell836.0 Primary mediastinal large B-cell332.4 Anaplastic large T/null-cell332.4 High grade B-cell, Burkitt-like292.1 Marginal zone B-cell, nodal25 1.8 Precursor T-lymphoblastic231.7 Lymphoplasmacytoid16 1.2 Marginal zone B-cell, splenic11< 1 Mycosis fungoides11< 1 Burkitts10< 1 Blood, Vol 89, No 11 (June 1), 1997: pp 3909-3918 Slide 43 Table 6. Patient Characteristics by Histologic Type %Median%Stage% Marr% PI% PI % 5-yr % 5-yr DiagnosisMaleAge 1 or 2 Pos 0/14/5OAS FFS Follicular, all grades 4259334239672 40 Mantle cell7463196319192711 Marginal zone B-cell, MALT45616614385 74 60 Marginal zone B-cell, nodal415818413695729 Small lymphocytic53 65 6 73 17 10 51 25 Lymphoplasmacytoid 5363207320135925 Diffuse large B-cell5564511731164641 Primary mediastinal large B-cell34376634495048 Burkitts8931563344224444 Burkitt-like5955502125184743 T-lymphoblastic7425134335222624 Peripheral T-cell, all types5661183714272518 Anaplastic large T/ null-cell6933501250197758 Blood, Vol 89, No 11 (June 1), 1997: pp 3909-3918 Slide 44 Table 7. Survival by Histologic Type and the International Prognostic Index immunologic data. For other types, such as the lymphoplas-macytoid, nodal marginal zone B-cell, and high-grade B-cell % 5-yr OAS % 5-yr FFS Burkitt-like lymphomas, imprecise histologic criteria and the Index Index Index Index lack of specific immunologic markers led to a diagnostic Consensus Diagnosis 0/1 4/5 0/1 4/5 accuracy of only 53% to 65%. Further definition of these Follicular, all grades 84 17 55 6 entities is clearly needed. Because the need for immunophe- Mantle cell 57 0 27 0 notyping cannot be predicted before biopsy, it is vital that Marginal zone B-cell, MALT 89 40 83 0 each patient have tissue available for immunophenotyping Marginal zone B-cell, nodal 76 50 30 0 and other special studies to facilitate proper patient care. In Small lymphocytic (CLL) 76 38 35 13 many cases, this will require communication between the Diffuse large B-cell 73 22 63 19 oncologist, the surgeon, and the pathologist. Primary mediastinal large B-cell 77 0 69 0 The 13 major types of NHL shown in Fig 1 made up over High grade B-cell, Burkitt-like 71 0 71 0 Precursor T-lymphoblastic 29 40 29 40 90% of the cases in our study, with diffuse large B-cell Peripheral T-cell, all types 36 15 27 10 lymphoma and follicular lymphoma comprising over 50% Anaplastic large T/null-cell 81 83 49 83 of the cases and the newly recognized entities comprising 21% of the cases (Table 3). The clinical features of the Abbreviations: PI, International Prognostic Index; OAS, overall sur-vival; FFS, failure-free survival; CLL, chronic lymphocytic leukemia. various lymphoma types were remarkably different, as were Blood, Vol 89, No 11 (June 1), 1997: pp 3909-3918 Slide 45 Slide 46 Slide 47 Slide 48 MACOP-B vs ProMACE-MOPP in the treatment of advanced diffuse NHL: results of a prospective randomized trial by the non-Hodgkin's Lymphoma Cooperative Study Group. ProMACE-MOPP MACOP-B CR49.1% 52.3% 3-year OS45.2%52.3% 3-yearPFS36.4%36.1% CONCLUSION: No significant differences in terms of efficacy and/or toxicity between ProMACE-MOPP and MACOP-B are evident. These results are consistent with recent randomized trials showing that the new- generation aggressive regimens are no better than previous ones. Sertoli-MR; et-al J-Clin-Oncol. 1994 12(7): 1366 Slide 49 Slide 50 Slide 51 Slide 52 Slide 53 Slide 54 Slide 55 Slide 56 Slide 57 Slide 58 Slide 59 Slide 60 Slide 61 Slide 62 Slide 63 Slide 64 Slide 65 Slide 66 Slide 67 Slide 68 Slide 69 Follicular low grade lymphoma Patients No 91 5 years survival66% median overall survival 111 months 5 years survival sexmale57% female73%0.03 age< 7067% > 7028%0.004 StageI or II89% III or IV57%0.06 B symptomsyes41% no69%0.03 Morel et al., Ann Hematol 66, 303, 1993 Slide 70 Intermediate/ high-grade lymphomas response rate treatmentNoO.R.C.R CHOP 22580%44% m-BACOD 22