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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.

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Presentation on theme: "GRADO INTERMEDIO Dfollicolare, prevalenza di grandi cellule Ediffuso, a piccole cellule clivate Fdiffuso, misto a piccole e grandi cellule Gdiffuso a grandi."— Presentation transcript:

1 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

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

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,

4 OS and IPI Age adjusted index, patients < 69 (n = 1274) Shipp N Engl J Med 329, 987, SONO TROPPPO BASSE

5 OS and IPI Age adjusted index, patients < 69 (n = 1274) Shipp N Engl J Med 329, 987, SONO TROPPPO BASSE

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9 EFS Fisher RI, et al. New Engl J Med 328, 1002, 1993

10 Overall survival Fisher RI, et al. New Engl J Med 328, 1002, 1993

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14 Dipartimento di Scienze Mediche, Oncologiche e Radiologiche - Università di Modena - Marzo 1998

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27 De vita, NEJM review Hodgkin

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29 Philip T. et al. New Engl J Med 333, 1540, 1995

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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

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

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

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

36 8 year OS ABMT64% (95% CI 55%-73%) CHT49% (95% CI 39%-59%)

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

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

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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: , 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.

41 Armitage, Cancer 63: , 1989.

42 Table 3. Distribution of NHL Cases by the Consensus Diagnosis % Diffuse large B-cell Follicular Marginal zone B-cell, MALT Peripheral T-cell Small B-lymphocytic (CLL) 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, nodal Precursor T-lymphoblastic231.7 Lymphoplasmacytoid Marginal zone B-cell, splenic11< 1 Mycosis fungoides11< 1 Burkitts10< 1 Blood, Vol 89, No 11 (June 1), 1997: pp

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 Mantle cell Marginal zone B-cell, MALT Marginal zone B-cell, nodal Small lymphocytic Lymphoplasmacytoid Diffuse large B-cell Primary mediastinal large B-cell Burkitts Burkitt-like T-lymphoblastic Peripheral T-cell, all types Anaplastic large T/ null-cell Blood, Vol 89, No 11 (June 1), 1997: pp

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 entities is clearly needed. Because the need for immunophe- Mantle cell notyping cannot be predicted before biopsy, it is vital that Marginal zone B-cell, MALT each patient have tissue available for immunophenotyping Marginal zone B-cell, nodal and other special studies to facilitate proper patient care. In Small lymphocytic (CLL) many cases, this will require communication between the Diffuse large B-cell oncologist, the surgeon, and the pathologist. Primary mediastinal large B-cell The 13 major types of NHL shown in Fig 1 made up over High grade B-cell, Burkitt-like Precursor T-lymphoblastic % of the cases in our study, with diffuse large B-cell Peripheral T-cell, all types lymphoma and follicular lymphoma comprising over 50% Anaplastic large T/null-cell 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

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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 (7): 1366

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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

70 Intermediate/ high-grade lymphomas response rate treatmentNoO.R.C.R CHOP 22580%44% m-BACOD 22382%48% Pro-MACE-CytaBOM 23387%56% MACOP-B 21883%51% Fisher et al, NEJM 328, 1002, 1993

71 Intermediate/ high-grade lymphomas response rate treatmentNoO.R.C.R CHOP 22580%44% m-BACOD 22382%48% Pro-MACE-CytaBOM 23387%56% MACOP-B 21883%51% Fisher et al, NEJM 328, 1002, 1993

72 Intermediate/ high-grade lymphomas 3 years overall survival treatmentNo CHOP 22554% m-BACOD 22352%P=0.9 Pro-MACE-CytaBOM 23350% MACOP-B 21850% Fisher et al, NEJM 328, 1002, 1993

73 Intermediate/ high-grade lymphomas 3 years overall survival treatmentNo CHOP 22554% m-BACOD 22352%P=0.9 Pro-MACE-CytaBOM 23350% MACOP-B 21850% Fisher et al, NEJM 328, 1002, 1993

74 Intermediate/ high-grade lymphomas 3 years D.F.S. treatmentNo CHOP 22541% m-BACOD 22346%P=0.35 Pro-MACE-CytaBOM 23346% MACOP-B 21841% Fisher et al, NEJM 328, 1002, 1993

75 Intermediate/ high-grade lymphomas 3 years D.F.S. treatmentNo CHOP 22541% m-BACOD 22346%P=0.35 Pro-MACE-CytaBOM 23346% MACOP-B 21841% Fisher et al, NEJM 328, 1002, 1993

76 Dipartimento di Scienze Mediche, Oncologiche e Radiologiche - Università di Modena - Marzo 1998

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88 Abstract: 575 (EBMT) Allogeneic stem cell transplantation for advanced hodgkin's disease: The M.D. Anderson experience P. Anderlini, B. Andersson, J. Gajewski, S. Giralt, R. Mehra, D. Claxton, N. Ueno, I. Khouri, D. Przepiorka, M. Donato, M. Körbling, R. Champlin M.D. Anderson Cancer Center, Houston, USA Since 1989 a total of nine allogeneic bone marrow (alloBMT) or blood stem cell transplantation (alloSCT) for relapsed/refractory Hodgkin's disease (HD) from HLA-identical related donors have been performed at MDACC. The results are as follows:

89 Time period present Stem cell sourceAlloBMT (n = 5)AlloSCT (n = 4). Median patient age (yrs)27 (23-41)30 (21-35) Conditioning regimenCBV (n = 3), Bu-Cy (n = 3), Bu-Cy (n = 2) other (n = 1) Status at transplantRefr (n = 1) Rel 2 or 3 (n = 4) rel 2/3 (n = 2), other (n = 2) Prior autologous BMT4/53/4 OutcomeExpired 5/5 Alive 4/4 (4 within 6 mos)(2 in remission) Median follow-up (mos)n.a.7 (2-10) P. Anderlini, e t al. EBMT 1998

90 The causes of death in the alloBMT pts. were relapse (n = 1), transplant-related mortality (TRM) (n = 3) and unknown (n = 1). Conclusions: (1) As reported in the literature (mainly from registry data), alloBMT in relapsed/refractory HD was associated with high TRM and relapse rates. (2) The reason for the seemingly improved early TRM and short-term outcome recently seen in allografted HD patients at MDACC is unclear. Several factors, such as better supportive care, FK506- based GVHD prophylaxis and possibly the introduction of alloSCTs and IV busulfan may be responsible for this very encouraging trend. P. Anderlini, e t al. EBMT 1998

91 patients number42 median age33 (16-56) follicular large cell6 diffuse mixed5 diffuse large cell21 immunoblastic10 stage III-IV37 (88%) bulky > 8 cm36 (86%) IPI High25 (60%) IPI HI17 (40%) Nademanee, Blood 90, 3844, 1997

92 standard intensive n.3433 median age49 (19-60)37 (23-60) centroblastic1819 immunoblastic21 T cell43 unclassified58 Ki-131 other21 bulky22/34 18/33 stage IV27/34 25/33 adverse features 223/3415/33 adverse features 311/3418/33 Pettengel J Clin Oncol 14, 586, 1996

93 standardintensive number6061 median age49(19-60)45 (18-60) large cleaved (G)3737 l.c. with LG component56 immunoblastic167 anaplastic211 stage II1718 stage III-IV4343 bulky > 10cm2631 bone marrow1015 adverse features adverse features Cortelazzo Br J Haematol 99, 379, 1997

94 CHOPm-BACODProMACE MACOP-B CytaBOM number age (median)56 (15-79)57 (18-81)54 (17-81)57 (19-79) > Bulky % Marrow % LDH >250 % WF group D-E F-G-H J5444 Fisher, NEJM 328, 1002, 1993

95 standard (50)intensive (48) age35 (17-60)34 (18-59) group G88%91% group H12%10% T cell00 stage I-II32%28% stage III-IV68%72% Marrow00 Bulky 70%76% IPI L-IL2%0 IPI HI-H74%94% Gianni et al, NEJM 336, 1290, 1997

96 TI: Comparison of a second-generation combination chemotherapeutic regimen (m-BACOD) with a standard regimen (CHOP) for advanced diffuse non-Hodgkin's lymphoma AU: Gordon-LI; Harrington-D; Andersen-J; Colgan-J; Glick-J; Neiman-R; Mann-R; Resnick-GD; Barcos-M; Gottlieb-A; et-al AD: Northwestern University Medical School, Department of Medicine, Chicago, IL SO: N-Engl-J-Med Nov 5; 327(19): AB: In 1984, the Eastern Cooperative Oncology Group began a randomized controlled clinical trial of patients with advanced (stage III or IV) diffuse mixed or diffuse large- cell lymphoma to determine whether complete-remission rates, survival, and toxicity differed when patients were treated with CHOP as compared with m-BACOD.

97 From July 1984 through January 1988, 392 patients were enrolled. After a median follow-up of four years, there were no significant differences in rates of complete remission, time to treatment failure, disease-free survival, or overall survival in the patients treated with CHOP as compared with those treated with m-BACOD. However, there was more severe and life-threatening pulmonary, infectious, and hematologic toxicity associated with the m-BACOD regimen. CONCLUSIONS. For patients with stage III or IV diffuse mixed or diffuse large-cell lymphoma, CHOP is superior to m-BACOD. Gordon-LI; et al. N-Engl-J-Med Nov 5; 327(19):

98 TI: Randomized comparison of MACOP-B with CHOP in patients with intermediate-grade non-Hodgkin's lymphoma. The Australian and New Zealand Lymphoma Group. AU: Cooper-IA; Wolf-MM; Robertson-TI; Fox-RM; Matthews-JP; Stone-JM; Ding-JC; Dart-G; Matthews-J; Firkin-FC; et-al AD: Department of Haematology and Medical Oncology, Peter MacCallum Cancer Institute, Melbourne, Victoria, Australia. SO: J-Clin-Oncol Apr; 12(4): Between October 1986 and June 1991, 304 patients were randomized to compare complete response rates, time to failure, survival, and toxicity for patients with intermediate-grade NHL treated with CHOP versus those treated with MACOP-B, in a multicenter, randomized controlled trial performed by 22 centers of the Australian and New Zealand Lymphoma Group (ANZLG).

99 RESULTS: There was no significant difference in complete response rates (51% for MACOP-B v 59% for CHOP), failure-free survival, or overall survival in the two treatment arms. Toxicity was significantly more severe with MACOP-B. CHOP remains the standard chemotherapy for this disease, against which all new regimens should be compared. Cooper-IA; et al. J-Clin-Oncol Apr; 12(4):

100 CASISTICA Pazienti 17 –sesso maschi 9 femmine 8 Età –media 39 (20-58) –mediana 41 CASISTICA Stato al trapianto RC 1 10 RP5 Recidiva >22 Patologia LNH 11 MdH 2 LLA 2 LMA 1 MM 1

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103 TI: Benefit of autologous bone marrow transplantation over sequential chemotherapy in poor-risk aggressive non-Hodgkin's lymphoma: updated results of the prospective study LNH87-2. Groupe d'Etude des Lymphomes de l'Adulte. AU: Haioun-C; Lepage-E; Gisselbrecht-C; Bastion-Y; Coiffier-B; Brice-P; Bosly-A; Dupriez-B; Nouvel-C; Tilly-H; Lederlin-P; Biron-P; Briere-J; Gaulard-P; Reyes- F AD: Hopital Henri Mondor, Creteil, France. SO: J-Clin-Oncol Mar; 15(3): PURPOSE: To compared consolidative sequential treatment (ifosfamide, etoposide, asparaginase, and cytarabine) versus the high-dose regimen of cyclophosphamide, carmustine, and etoposide (CBV) followed by autotransplantation in patients with aggressive non-Hodgkin's lymphoma in first complete remission.

104 541 patients in complete remission were assigned to receive consolidation by either sequential chemotherapy (n = 273) or autotransplant (n = 268). In the higher risk population: 5 years estimated DFSOS CBV 59% 65% CHT39% 52% P =.01 P =.06 CONCLUSION: Dose-intensive consolidation therapy should be considered for patients at higher risk who achieve complete remission after induction treatment. Haioun-C; et al-J-Clin-Oncol Mar; 15(3):

105 TI: Single and double autotransplants for relapsing/refractory Hodgkin's disease: results of two consecutive trials. AU: Ahmed-T; Lake-DE; Beer-M; Feldman-EJ; Preti- RA; Seiter-K; Helson-L; Mittelman-A; Kancherla-R; Ascensao-J; Akhtar-T; Cook-P; Goldberg-R; Coleman-M AD: Division of Oncology and Hematology, New York Medical College, Valhalla 10595, USA. SO: Bone-Marrow-Transplant Mar; 19(5): AB: Patients with refractory disease were offered a second transplant with different conditioning in the absence of progression or excessive toxicity. 45 refractory patients (24 with primary refractory disease and 21 with refractory relapse) received a second cycle. After the first cycle, 12 were in CR and 11 in PR and 10 of these 11 in PR achieved a durable CR with the second transplant.

106 The CR rate is 37% in patients with refractory relapse and 19% in those with primary refractory disease. At a median follow-up of 4 years, median survival is 45 months. Progression-free survival of the refractory patients who could receive a second cycle was similar to that of patients with sensitive disease. Conclusion A sequential transplant strategy is feasible. A subgroup of patients with refractory disease can achieve long-term survival after sequential BMT. Ahmed-T; et al. Bone-Marrow-Transplant Mar; 19(5):

107 BEC-2BCNU400 mg/m2 day -5 VP mg/m2 day -5 cyclophosphamide 2500 mg /m2 days -5 and -4 TMJThiotepa 250 mg/m2 days -7, -6, -5 Mitoxantrone 40 mg/m2 day -7 Carboplatin 330 mg/m2 days -7, -6, -5 Ahmed-T; et al. Bone-Marrow-Transplant Mar; 19(5):

108 CONDIZIONAMENTO BEAM 12 CBV 1 BuCy 1 MTM 2 HD L-PAM 1 REGIME DI CONDIZIONAMENTO

109 RISULTATI ATTECCHIMENTO17/17(100%) VIVI17/17(100%) –in remissione15/17 –in recidiva2/17(12%) T.R.M. 0/17(0%) Follow-up –media5 mesi(1-10) –mediana5 mesi

110 Linfomi CHOP 4 cicli Cy 4gr/m2 +G-CSF PBPCs HD CHT (BEAM) diagnosi reinfusione - conta CD34 - colonie - citogenetica - diagnostica molecolare - criopreservazione

111 NHL INTERMEDIATE/HIGH GRADE AUTOGRAFTING CR 2 n = 472 CR 1 n = % 63% PFS % EBMT registry 1995 years

112 NHL at relapse disease free survival % sensitive relapse resistant relapse years after transplantation 678

113 Trapianto Autologo Perché nei linfomi?

114 TI: Autologous bone marrow transplantation in poor-prognosis intermediate-grade and high-grade B-cell non-Hodgkin's lymphoma in first remission: a pilot study. AU: Freedman-AS; Takvorian-T; Neuberg-D; Mauch-P; Rabinowe-SN; Anderson-KC; Soiffer- RJ; Spector-N; Grossbard-M; Robertson-MJ; et-al AD: Division of Tumor Immunology, Dana- Farber Cancer Institute, Boston, MA SO: J-Clin-Oncol May; 11(5): 931-6

115 AB: Twenty-six patients with advanced-stage diffuse intermediate/high-grade B-cell NHL (including 16 patients with diffuse small cleaved- cell [DSC]) were selected at presentation by histologic and clinical characteristics to have less than a 25% probability of long-term DFS with conventional treatment. After induction chemotherapy, 16 patients were in complete remission (CR) and 10 were in a minimal disease state. Patients were then treated with high-dose cyclophosphamide, total-body irradiation (TBI), and anti-B-cell monoclonal antibody-purged ABMT. Freedman-AS; et al., J-Clin-Oncol May; 11(5): 931-6

116 RESULTS: no acute in-hospital treatment deaths occurred. The median follow-up period for the 21 patients who are alive and disease-free is 32 months. The DFS rate is estimated to be 85% at 28 months and thereafter. CONCLUSION: This pilot study suggests that consolidation of first remission with ABMT may improve the long-term DFS rate for diffuse intermediate/high-grade NHL patients at high risk for relapse. Freedman-AS; et al., J-Clin-Oncol May; 11(5): 931-6

117 A phase II multicenter trial of high-dose sequential chemotherapy and peripheral blood stem cell transplantation as initial therapy for patients with high-risk non-Hodgkin's lymphoma. Schenkein-DP; et al. (Tupper Research Institute, New England Medical Center, Boston, MA, USA). Biol-Blood-Marrow-Transplant Oct; 3(4): 210-6

118 Thirty-two patients with high-risk NHL (defined by the age-adjusted international index) underwent HDS chemotherapy followed by PBSC transplantation. HDS consisted of Phase I (adriamycin, vincristine, and prednisone); Phase II (cyclophosphamide, filgrastim [G-CSF], and PBSC harvest); Phase III (methotrexate, leucovorin, vincristine; Phase IV (etoposide, filgrastim [G-CSF]); and Phase V (mitoxantrone, melphalan, autologous peripheral blood stem cell infusion, and filgrastim [G-CSF]). Radiation therapy was given to sites of previous bulk disease, 2400 cGy, (D )]. Schenkein-DP; et al. Biol-Blood-Marrow-Transplant Oct; 3(4): 210-6

119 TRM6.25% median follow-up 18.8 months (4-44) OS at 18 months78% (95% CI 37-90%) RFS at 18 months67% (95% CI 46-88%) High-dose sequential chemotherapy with initial PBSC transplantation is well tolerated and appears effective in high-risk NHL. Superior results were noted in patients with intermediate grade versus those with small noncleaved or lymphoblastic NHL. Schenkein-DP; et al. Biol-Blood-Marrow-Transplant Oct; 3(4): 210-6

120 TI: Autotransplantation for relapsed or refractory non-Hodgkin's lymphoma (NHL): long-term follow-up and analysis of prognostic factors. AU: Rapoport-AP; et. al. AD: Department of Medicine, University of Rochester, School of Medicine and Dentistry, NY, USA. SO: Bone-Marrow-Transplant May; 19(9):

121 AB: One hundred and thirty-six patients autografted for relapsed or refractory non-Hodgkin's lymphoma (NHL) were evaluated to assess long- term event-free survival and to identify important prognostic factors. Patients were treated with 1-3 cycles o DHAP or other regimens until a complete response was obtained or there was no significant change and riceived high-dose therapy (primarily carmustine (BCNU), etoposide, cytarabine, and cyclophosphamide (BEAC)) followed by unpurged autologous stem cell rescue. Rapoport-AP; et. al. Bone-Marrow-Transplant May; 19(9):

122 TRM4.4%. 5-year EFS34% (95% CI 24-44%) median FU3 years (range years). New strategies are needed to reduce the high rate of relapse (50-60%) following auto-transplantation for relapsed or refractory NHL. Rapoport-AP; et al. Bone-Marrow-Transplant May; 19(9):

123 TI: Primary diffuse large B-cell lymphoma of the mediastinum: outcome following high-dose chemotherapy and autologous hematopoietic cell transplantation. AU: Sehn-LH; Antin-JH; Shulman-LN; Mauch-P; Elias-A; Kadin-ME; Wheeler-C AD: Hematology-Oncology Division, Brigham and Women's Hospital, Boston, MA, USA. SO: Blood Jan 15; 91(2): AB: We performed a retrospective analysis of 35 patients with primary diffuse large B-cell lymphoma of the mediastinum treated with high-dose cyclophosphamide, carmustine, and etoposide (CBV) plus autologous hematopoietic cell transplantation to determine outcome and prognostic features for progression-free survival (PFS).

124 Patients transplanted in first response had an estimated 5-year PFS rate of 83%, compared with 58% and 27% for primarily refractory and relapsed patients, respectively (P =.02). The strongest predictor of PFS was chemotherapy responsiveness immediately before transplantation. Sehn-LH; et al., Blood Jan 15; 91(2):

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137 AGGRESSIVE REALWorking FormulationKielLineage Follicular centerD. FollicularCentroblasticB (grade III)predominantly(follicular) large cell Mantle cellE: Diffuse small CentrocyticB cleaved cells F. Diffuse mixed small and large cell Diffuse large G. Diffuse largeCentroblasticB B-cell cell(diffuse) H. Large cell immunoblastic Primary mediastinalG. Diffuse largeLarge cell. B (thymic) B cellcellsclerosing B cell lympohoma of mediastinum

138 AGGRESSIVE REALWorking FormulationKielLineage PeripheralF. Diffuse mixedLymphoepiteliod, T-cellsmall and large cellpleiomorphic (small.T G. Diffuse large cellmedium or H. Large celllarge cell) immunoblastic AngioimmunoblasticAngioimmunoblasticT T cell Adult T cellPleiomorphicT lymphoma/leukemia(small, medium or large cell HTLV +) AngiocentricPleiomorphicT Intestinal T cell(small, medium or large cell

139 AGGRESSIVE REALWorking FormulationKielLineage AnaplasticH. Large cellLarge cellT (70%) large cellimmunoblasticanaplasticnull (30%) (Ki-1+) LymphoblaasticI. LymphoblasticLymphoblasticT (90%) lymphomaB (10%) Lymphoblastic Leukemia BurkittsJ. Small non cleavedBurkittsB (95%) cell; BurkittsT (5%)

140 HDT + auto HSCs prolunga il DFS (studi randomizzati) NHL at relapse (Philip et al., N Eng l J Med 333, 1540, 1995) AML RC1 (Zittoun et al., N Engl J Med 332, 217, 1995) MM at diagnosis (Attal et al., N Engl J Med 335, 91, 1996) NHL at diagnosis (Gianni) N Engl J Med 336, 1290, 1997

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142 TI: Chlorambucil/prednisone vs. CHOP in symptomatic low-grade non-Hodgkin's lymphomas: a randomized trial from the Lymphoma Group of Central Sweden. AU: Kimby-E; Bjorkholm-M; Gahrton-G; Glimelius-B; Hagberg- H; Johansson-B; Johansson-H; Juliusson-G; Jarnmark-M; Lofvenberg-E; et-al AD: Dept of Medicine, Danderyd Hospital, Sweden. SO: Ann-Oncol. 1994; 5 Suppl 2: AB: Two hundred fifty-nine previously untreated patients with low-grade non-Hodgkin's lymphomas (NHLs), Ann Arbor stages III and IV, entered a randomized multicenter trial comparing the therapeutic effect of chlorambucil/prednisone (ChP) vs. CHOP. All patients had symptomatic disease.

143 ChPCHOP N R.R. (CR+PR at 8 months)36%60% p < year survival59%64% n.s. 5-year survival41%44% n.s. *corrected 5-year survival49%54% n.s. median survival months4652 n.s. *After correction for intercurrent deaths Kimby-E et al., Ann-Oncol. 1994; 5 Suppl 2: 67-71

144 The median survival time from diagnosis was 68 months, with no differences between the treatment groups. In all histological subgroups (CLL, IC, CC, and CB-CC), a higher remission rate was seen with the CHOP regimen but with no statistically significant influence on survival. Comparing patients below and above 65 years of age, no significant difference in survival was noted between the two treatment groups. The results do not support the use of intensive chemotherapy as first-line therapy in symptomatic low-grade NHL. Kimby-E et al., Ann-Oncol. 1994; 5 Suppl 2: 67-71

145 BEAM chemotherapy followed by autologous stem cell support in lymphoma patients: analysis of efficacy, toxicity and prognostic factors. Caballero-MD, et al. Bone-Marrow- Transplant. 20, 451, 1997 AB: Patients with NHL (n = 112) received BEAM followed by infusion of bone marrow (n = 55), peripheral blood stem cells (n = 79) or both (n = 14): 78% were in CR following ASCT, including 25 out of 45 patients (56%) who were transplanted with active disease.

146 Only two of the 11 patients transplanted with resistant disease achieved CR. In conclusion, the present results demonstrate the efficacy and low toxicity of the BEAM regimen in high-risk lymphoma patients with sensitive disease. Other strategies should be investigated for patients with refractory lymphoma. Caballero-MD, et al. Bone-Marrow-Transplant. 20, 451, 1997

147 TI: Results of high-dose therapy and autologous bone marrow/stem cell transplantation during remission in poor-risk intermediate- and high-grade lymphoma: international index high and high- intermediate risk group. AU: Nademanee-A; et al. AD: Department of Hematology and Bone Marrow Transplantation, City of Hope National Medical Center, Duarte, CA, USA. - Bone Marrow Transplant Programme, Stanford University Medical Center, Stanford, CA SO: Blood Nov 15; 90(10): AB: We have conducted a pilot study to investigate the role of high-dose therapy and autologous bone marrow/stem cell transplantation (ASCT) during first complete or partial remission in 52 patients with poor- risk aggressive lymphoma..

148 patients number42 median age33 (16-56) follicular large cell6 diffuse mixed5 diffuse large cell21 immunoblastic10 stage III-IV37 (88%) bulky > 8 cm36 (86%) IPI High25 (60%) IPI HI17 (40%) Nademanee, Blood 90, 3844, 1997

149 Thirty-nine were transplanted in first complete remission and 13 in first partial remission after conventional therapy. Conditioning regimens consisted of total body irradiation (TBI) administered as a single fraction 750 cGy in 3 patients and in fractionated doses for a total of 1,200 cGy in 44 patients, in combination with 60 mg/kg etoposide and 100 mg/kg cyclophosphamide. Five patients with prior radiotherapy received 450 mg/m2 carmustine instead of TBI. Stem cell sources were either bone marrow and/or peripheral blood. No in vitro purging was used. Nademanee-A; et al., Blood Nov 15; 90(10):

150 FU median44 months (1-113) estimated 3-year OS84% (95% CI 70% to 92%) estimated 3-year DFS82% (95% CI, 68% to 91%) These results suggest that high-dose therapy and ASCT during first remission may improve the survival and prognosis of patients with poor-risk intermediate- and high-grade lymphoma. A prospective randomized study comparing high-dose therapy and ASCT with conventional chemotherapy in IPI high-risk patients with aggressive non-Hodgkin's lymphoma should be undertaken. Nademanee-A; et al., Blood Nov 15; 90(10):

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152 standard intensive n.3433 median age49 (19-60)37 (23-60) centroblastic1819 immunoblastic21 T cell43 unclassified58 Ki-131 other21 bulky22/34 18/33 stage IV27/34 25/33 adverse features 223/3415/33 adverse features 311/3418/33 Pettengel J Clin Oncol 14, 586, 1996

153 standardintensive number6061 median age49(19-60)45 (18-60) large cleaved (G)3737 l.c. with LG component56 immunoblastic167 anaplastic211 stage II1718 stage III-IV4343 bulky > 10cm2631 bone marrow1015 adverse features adverse features Cortelazzo Br J Haematol 99, 379, 1997

154 CHOPm-BACODProMACE MACOP-B CytaBOM number age (median)56 (15-79)57 (18-81)54 (17-81)57 (19-79) > Bulky % Marrow % LDH >250 % WF group D-E F-G-H j5444 Fisher, NEJM 328, 1002, 1993

155 standard (50)intensive (48) age35 (17-60)34 (18-59) group G88%91% group H12%10% T cell00 stage I-II32%28% stage III-IV68%72% Marrow00 Bulky 70%76% IPI L-IL2%0 IPI HI-H74%94% Gianni et al, NEJM 336, 1290, 1997

156 TI: Autologous stem cell transplantation for aggressive non-Hodgkin's lymphomas in first complete or partial remission: a retrospective analysis of the outcome of 52 patients according to the age- adjusted International Prognostic Index. AU: Fanin-R; Silvestri-F; Geromin-A; Infanti-L; Sperotto-A; Cerno-M; Stocchi-R; Savignano-C; Rinaldi- C; Damiani-D; Baccarani-M AD: Department of Medical and Morphological Research, University Hospital, Udine, Italy. SO: Bone-Marrow-Transplant Feb; 21(3):

157 Fifty-two consecutive patients, aged less than 60 years, with intermediate- or high-grade NHL, and at least one of the following adverse risk factors: bulky disease, B symptoms or Ann Arbor stage III-IV, and at least a PR after CHT (and radiotherapy (RT) on residual mediastinal mass when required), underwent ASCT conditioned with BAVC. Sixty-five percent (33/52) of the patients achieved CR after CHT; 69% (36/52) after CHT + RT; 90% (47/52) after CHT +/- RT + ASCT. One death during conditioning and three major toxic events after ASCT were recorded. Overall survival (OS) is 98% at 37 months (16-88); disease-free survival (DFS) is 100% at 27 months (7-82). Fanin-R. et al., Bone-Marrow-Transplant. 1998, 21, 263

158 Comparing the observed results with those expected if patients were treated only with CHT, the sequential treatment including ASCT conferred an advantage in terms of CR rate of 14, 23 and 54%, respectively, in the low-intermediate (LI), high- intermediate (HI) and high (H)-risk groups, respectively. The 2-year OS advantage is 10, 21, 31 and 63%, respectively, and the 2-year DFS advantage is 12, 26, 38 and 39%, respectively. Even more striking is the 5-year projected advantage in the number of patients alive without disease, even when considering only the low (L) (P < ) and the LI (P < ) risk groups. Fanin-R. et al., Bone-Marrow-Transplant. 1998, 21, 263

159 For patients in the higher (HI + H) risk groups, ASCT should be included in the initial plan of treatment as consolidation of first CR or PR The differences seen in this study suggest a formal comparison in a randomized study also for patients in the LI risk group. Fanin-R. et al., Bone-Marrow-Transplant. 1998, 21, 263

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161 pazienti51 sessomaschi30 femmine21 etàmedia42 mediana43 range15-65 LINFOMI - Trapianto autologo 1 ottobre 98 Dipartimento di Oncoematologia - Università di Modena

162 Tipo istologico (WF): A-B-C9 (17,6%) D-E-F-G31 (60,7%) H-I-J11 (21,5%) LineaB 39 T8 nd4 LINFOMI - Trapianto autologo 2 Dipartimento di Oncoematologia - Università di Modena ottobre 98

163 stadioII7 (13.7%) III12 (23,5%) IV32 (62.7%) Bulky33/50 (66%) Midollo + 19/46 (41,3%) LINFOMI - Trapianto autologo 3 Dipartimento di Oncoematologia - Università di Modena ottobre 98

164 Prospective randomized trial by the NHL Cooperative Study Group: 221 patients with intermediate- high grade NHL (Working Formulation F, G, H, K): 3 yearsCROSPFS MACOP-B52%52%36% ProMACE-MOPP49%45%36% Conclusion: NO significant differences Sertoli MR et al. J Clin Oncol 12, 1366, 1994

165 MACOP-B +/- radiatio therapy fo diffuse olarge cell lymphoma. Analysis of the stanford results according to prognostic indices. n3 year FFP 4752% Compared to historical CHOP data, MACOP-B does not appear to improve outcome for patients with poor prognostic features Bartlett NL, et al Cancer 71, 4034, 1993

166 Intermediate- high grade NHL 4 yearsnCR RFS ProMECE-CytaBOM10662%59% MACOP-B10467%69% p 0.11 Silingardi V. et al, Leuk-Lymphoma 17, 313, 1995

167 Lineaprima45 recidiva6 RegimeBEAM41 HDS7 TBI-Cy1 altro2 LINFOMI - Trapianto autologo 4 ottobre 98 Dipartimento di Oncoematologia - Università di Modena

168 Università di Modena - Azienda Policlinico Dipartimento di Scienze Mediche, Oncologiche e Radiologiche Linfomi 51 LINFOMI - Trapianto autologo 5

169 Università di Modena - Azienda Policlinico Dipartimento di Scienze Mediche, Oncologiche e Radiologiche Trapianti 148

170 Stato pre-trapiantoRisposta Valutati 44Valutati 47 RC27 (61,3%)RC46 (97,8%) VGPR6 (13,6%)RP1 RP6 (13,6%) Refractory1 n.v. (HDS)7n.v. (F.U.)5 LINFOMI - Trapianto autologo 6 ottobre 98 Dipartimento di Oncoematologia - Università di Modena

171 Pazienti51 FU (dal trapianto) mesimediana21 (1-41) vivi45/51 (88%)vivi RC43 (84%) vivi Rec2 (4%) deceduti6/51 (12%)T.R.M.1 (2%) D.R.M.5 (10%) Totale recidive7/51 (14%) LINFOMI - Trapianto autologo 7 ottobre 98 Dipartimento di Oncoematologia - Università di Modena

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176 Diversi studi ormai suggeriscono che HD-CHT è globalmente superiore in pazienti con malattia chemiosensibile la tossicità è accettabile Problemi: conferma da studi prospettici randomizzati fattibile ? selezione dei pazienti (overtreatment, costi) individuare fattori di rischio timing e strategia: allesordio o come consolidamento? Purging? non è la soluzione per pazienti con malattia refrattaria

177 High-Dose Therapy With Autologous Hematopoietic Rescue for Follicular Low-Grade Non-Hodgkin's Lymphoma By Philip J. Bierman, Julie M. Vose, James R. Anderson, Michael R. Bishop, Anne Kessinger, and James O. Armitage J Clin Oncol 15: Patients and Methods: We performed a retrospective review of 100 patients undergoing autologous transplantation for follicular low-grade lymphoma between April 22, 1983 and December 31, 1993.

178 Results: Sixty-seven patients remained alive and 48 were failure-free. The median follow-up duration of surviving patients was 2.6 years (range, 1.0 to 11.7). There were eight (8%) deaths within 100 days of transplantation. Six additional patients died of nonrelapse causes up to 912 days after transplantation. Overall survival at 4 years was estimated to be 65% (95% confidence interval [CI], 54% to 75%) and failure-free survival was estimated to be 44% (95% CI, 33% to 55%). There was no definite evidence of a plateau in the failure-free survival curve. J Clin Oncol 15:

179 The only factor significantly associated with overall survival and failure-free survival was the number of chemotherapy regimen received before transplantation. No significant differences in outcome were observed between patients with follicular small cleaved-cell lymphoma and follicular mixed lymphoma, or between patients who received peripheral-blood stem-cell transplants and unpurged autologous bone marrow transplants. Conclusion: Prolonged failure-free survival is possible following high-dose therapy and autologous hematopoietic rescue for follicular low-grade lymphoma. It is unclear whether patients are cured with this therapy or if survival is prolonged. J Clin Oncol 15:

180 Donor Leukocyte Infusions in 140 Patients With Relapsed Malignancy After Allogeneic Bone Marrow Transplantation By Robert H. Collins, Jr, Ofer Shpilberg, William R. Drobyski, David L. Porter, Sergio Giralt, Richard Champlin, Stacey A. Goodman, Steven N. Wolff, Wendy Hu, Catherine Verfaillie, Alan List, William Dalton, Nadine Ognoskie, Angela Chetrit, Joseph H. Antin, and John Nemunaitis Patients and Methods: We surveyed 25 North American BMT programs regarding their use of donor leukocyte infusions (DLI). Reports of 140 patients were thus available for analysis.

181 Results: Complete responses were observed in 60% (95% confidence interval [CI], 51.9% to 68.1%) of chronic myelogenous leukemia (CML) patients who received DLI and did not receive pre-DLI chemotherapy; response rates were higher in patients with cytogenetic and chronic-phase relapse (75.7%; 95% CI, 68.2% to 83.2%) than in patients with accelerated-phase (33.3%; 95% CI, 19.7% to 46.9%) or blastic-phase (16.7%; 95% CI, 1.9% to 31.9%) relapse. The actuarial probability of remaining in complete remission at 2 years was 89.6%. Complete remission rates in acute myelogenous leukemia (AML) (n = 39) and acute lymphocytic leukemia (ALL) (n = 11) patients who had not received pre-DLI chemotherapy were 15.4% (95% CI, 9.6% to 21.2%) and 18.2% (95% CI, 6.6% to 29.8%), respectively. Complete remissions were also observed in two of four assessable myeloma patients and two of five assessable myelodysplasia patients. Complications of DLI included acute graft-versus-host disease (GVHD) (60%; 95% CI, 51.4% to 68.6%), chronic GVHD (60.7%; 95% CI, 50.3% to 71.1%), and pancytopenia (18.6%; 95% CI, 12.2% to 25.0%). Conclusion: DLI results in complete remissions in a high percentage of patients with relapsed chronic-phase CML. Complete remissions are observed less frequently in patients with advanced CML and acute leukemia. GVHD and pancytopenia occur commonly; GVHD is highly correlated with response. J Clin Oncol 15:

182 Hyper-CVAD and High-Dose Methotrexate/Cytarabine Followed by Stem-Cell Transplantation: An Active Regimen for Aggressive Mantle-Cell Lymphoma By Issa F. Khouri, Jorge Romaguera, Hagop Kantarjian, J. Lynn Palmer, William C. Pugh, Martin Korbling, Fredrick Hagemeister, Barry Samuels, Alma Rodriguez, Sergio Giralt, Anas Younes, Donna Przepiorka, David Claxton, Fernando Cabanillas, and Richard Champlin Purpose: Diffuse and nodular forms of mantle-cell lymphoma (MCL) are consistently associated with poor prognosis. J Clin Oncol 16:

183 In an effort to improve the outcome, we adopted a treatment plan that consisted of four courses of fractionated cyclophosphamide (CY) 1,800 mg/m2 administered with doxorubicin (DOX), vincristine (VCR), and dexamethasone (Hyper- CVAD) that alternated with high-dose methotrexate (MTX) and cytarabine (Ara-C). After four courses, patients were consolidated with high-dose CY, total-body irradiation, and autologous or allogeneic blood or marrow stem-cell transplantation. Patients and Methods: Forty-five patients were enrolled; 25 patients were previously untreated, 43 patients had Ann Arbor stage IV disease, and 42 patients had marrow involvement. Forty-one patients had diffuse histology, two patients had nodular, and two patients had blastic variants. J Clin Oncol 16:

184 Results: Hyper-CVAD/MTX-Ara-C induced a response rate of 93.5% (complete response [CR], 38%; partial response [PR], 55.5%) after four cycles of pretransplantation induction chemotherapy. All patients who went on to undergo transplantation achieved CRs. For the 25 previously untreated patients, the overall survival (OS) and event-free survival (EFS) rates at 3 years were 92% (95% confidence interval [CI], 80 to 100) and 72% (95% CI, 45 to 98) compared with 25% (95% CI, 12 to 62; P =.005) and 17% (95% CI, 10 to 43; P =.007), respectively, for the previously treated patients. When compared with a historic control group who received CHOP-like regimen, untreated patients in the study had a 3-year EFS rate of 72% versus 28% (P =.0001) and a better OS rate (92% v 56%; P =.05). J Clin Oncol 16:

185 Treatment-related death occurred in five patients: all were previously treated and two received allogeneic transplants. Conclusion: The Hyper-CVAD/MTX-Ara-C program followed by stem-cell transplantation is a promising new therapy for previously untreated patients with MCL. J Clin Oncol 16:

186 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,

187 NHL - Overall Survival 49% 64% p = 0.4 high intermediate and high risk patients Haioun et al, J Clin Oncol 18, 3025, 2000

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192 BEAM chemotherapy followed by autologous stem cell support in lymphoma patients: analysis of efficacy, toxicity and prognostic factors. Caballero-MD, et al. Bone-Marrow- Transplant. 20, 451, 1997 AB: Patients with NHL (n = 112) received BEAM followed by infusion of bone marrow (n = 55), peripheral blood stem cells (n = 79) or both (n = 14): 78% were in CR following ASCT, including 25 out of 45 patients (56%) who were transplanted with active disease.

193 BEAM chemotherapy followed by autologous stem cell support in lymphoma patients: analysis of efficacy, toxicity and prognostic factors. Caballero-MD, et al. Bone-Marrow- Transplant. 20, 451, 1997 AB: Patients with NHL (n = 112) received BEAM followed by infusion of bone marrow (n = 55), peripheral blood stem cells (n = 79) or both (n = 14): 78% were in CR following ASCT, including 25 out of 45 patients (56%) who were transplanted with active disease.

194 Only two of the 11 patients transplanted with resistant disease achieved CR. In conclusion, the present results demonstrate the efficacy and low toxicity of the BEAM regimen in high-risk lymphoma patients with sensitive disease. Other strategies should be investigated for patients with refractory lymphoma. Caballero-MD, et al. Bone-Marrow-Transplant. 20, 451, 1997

195 Gianni A.M. et al. N Engl J Med 336, 1290, 1997 MACOP-BHDS-CHT RC70%96%P=0.001 FFP49%84%P<0.001 FFR70%88%P=0.055 EFS49%76%P=0.004 OS 7 years55%81%P=0.09

196 Only two of the 11 patients transplanted with resistant disease achieved CR. In conclusion, the present results demonstrate the efficacy and low toxicity of the BEAM regimen in high-risk lymphoma patients with sensitive disease. Other strategies should be investigated for patients with refractory lymphoma. Caballero-MD, et al. Bone-Marrow-Transplant. 20, 451, 1997

197 Fisher, Cancer Chemother Pharmacol 1997, 40:suppl S42 6 yearOSPFS ProMACE CytaBOM46%34% MACOP-B41%32% m-BACOD40%36% CHOP42%33%

198 Fisher, Cancer Chemother Pharmacol 1997, 40:suppl S42 6 yearOSPFS ProMACE CytaBOM46%34% MACOP-B41%32% m-BACOD40%36% CHOP42%33%

199 Fisher, Cancer Chemother Pharmacol 1997, 40:suppl S42 Quali approcci sperimentali? 1. aumentare la dose intensity dei farmaci già in uso nei protocolli standard 2. Terapia sovramassimale e rescue con progenitori emopoietici autologhi (midollo o periferiche) 3. Nuovi farmaci (ndr) oggi: monoclonali allogenico

200 Fisher, Cancer Chemother Pharmacol 1997, 40:suppl S42 Quali approcci sperimentali? 1. aumentare la dose intensity dei farmaci già in uso nei protocolli standard 2. Terapia sovramassimale e rescue con progenitori emopoietici autologhi (midollo o periferiche) 3. Nuovi farmaci (ndr) oggi: monoclonali allogenico

201 Se un paziente non vuole partecipare ad uno studio clinico, il CHOP rimane il gold standard poiché i pazienti guariti dalla chemioterapia sono <50%, sono giustificati approcci terapeutici sperimentali per migliorare la nostra possibilità di curarare la malattia Fisher, Cancer Chemother Pharmacol 1997, 40:suppl S42

202 Se un paziente non vuole partecipare ad uno studio clinico, il CHOP rimane il gold standard poiché i pazienti guariti dalla chemioterapia sono <50%, sono giustificati approcci terapeutici sperimentali per migliorare la nostra possibilità di curarare la malattia Fisher, Cancer Chemother Pharmacol 1997, 40:suppl S42

203 NHL: PARMA protocol 215 patients at relapse DHAP BM harvesting N.R. out responders (109) DHAP X 4 ABMT Philip et al., N Eng l J Med 333, 1540, 1995)

204 rispetto alla terapia convenzionale il trapianto autologo porta ad un aumento della OS e della EFS per il futuro dovremmo condurre studi che consentano di stabilire se la tossicità può essere ridotta dallimpiego di cellule staminali periferiche e di fattori di crescita Philip NEJM 333, 1540, 1995 ABMT vs CHT in relapsed CHT sensitive NHL

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