11 results on '"Eric Deconninck"'
Search Results
2. Front-line high-dose chemotherapy with rituximab showed excellent long-term survival in adults with aggressive large b-cell lymphoma: final results of a Phase II GOELAMS Study
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Eric Deconninck, Philippe Casassus, Thierry Lamy, Diane Damotte, Marie-Sarah Dilhuydy, Christine Le Maignan, Remy Gressin, Noel Milpied, Charles Foussard, Service des maladies du sang, CHU Bordeaux [Bordeaux]-Hôpital Haut-Lévêque [CHU Bordeaux], CHU Bordeaux [Bordeaux]-Groupe Hospitalier Sud, Service d'hématologie clinique, Université de Rennes (UR)-Hôpital Pontchaillou, Service d'hématologie, Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM)-PRES Université Nantes Angers Le Mans (UNAM)-Hôtel Dieu, Département de cancérologie et d'hématologie, CHU Grenoble-Hôpital Michallon, Service d'hématologie clinique [Avicenne], Université Paris 13 (UP13)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Avicenne [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon), Interactions hôte-greffon-tumeur, ingénierie cellulaire et génique - UFC (UMR INSERM 1098) (RIGHT), Institut National de la Santé et de la Recherche Médicale (INSERM)-Etablissement français du sang [Bourgogne-Franche-Comté] (EFS [Bourgogne-Franche-Comté])-Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC), Service d'hématologie A [CHU HEGP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Européen Georges Pompidou [APHP] (HEGP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO), Service d'anatomo-pathologie [CHU HEGP], Saas, Philippe, CHU Bordeaux [Bordeaux]-Groupe Hospitalier Sud-Hôpital Haut-Lévêque [CHU Bordeaux], CHU Bordeaux [Bordeaux], Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Hôpital Pontchaillou, Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC)-Etablissement français du sang [Bourgogne-Franche-Comté] (EFS [Bourgogne-Franche-Comté]), Université de Rennes 1 ( UR1 ), Université de Rennes ( UNIV-RENNES ) -Université de Rennes ( UNIV-RENNES ) -Hôpital Pontchaillou, CHU Angers-Hôtel Dieu, Université Paris 13 ( UP13 ) -Assistance publique - Hôpitaux de Paris (AP-HP)-Hôpital Avicenne, Centre Hospitalier Régional Universitaire [Besançon] ( CHRU Besançon ) -hopital Jean Minjoz, Interactions hôte-greffon-tumeur, ingénierie cellulaire et génique - UFC (UMR INSERM 1098) ( HOTE GREFFON ), Université de Franche-Comté ( UFC ) -Etablissement français du sang [Bourgogne-France-Comté] ( EFS [Bourgogne-France-Comté] ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Assistance publique - Hôpitaux de Paris (AP-HP)-Hôpital Européen Georges Pompidou [APHP] ( HEGP ), and Institut National de la Santé et de la Recherche Médicale (INSERM)-Etablissement français du sang [Bourgogne-Franche-Comté] (EFS BFC)-Université de Franche-Comté (UFC) more...
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Male ,Oncology ,Aggressive lymphoma ,Immunochemotherapy ,Antibodies, Monoclonal, Murine-Derived ,0302 clinical medicine ,International Prognostic Index ,Risk Factors ,immune system diseases ,hemic and lymphatic diseases ,Antineoplastic Combined Chemotherapy Protocols ,[ SDV.IMM ] Life Sciences [q-bio]/Immunology ,High-dose therapy ,B-cell lymphoma ,Remission Induction ,Cytarabine ,Hematopoietic Stem Cell Transplantation ,Antibodies, Monoclonal ,Hematology ,Middle Aged ,3. Good health ,Survival Rate ,030220 oncology & carcinogenesis ,[SDV.IMM]Life Sciences [q-bio]/Immunology ,Female ,Rituximab ,Lymphoma, Large B-Cell, Diffuse ,medicine.drug ,Adult ,medicine.medical_specialty ,Adolescent ,[SDV.IMM] Life Sciences [q-bio]/Immunology ,Transplantation, Autologous ,Disease-Free Survival ,Drug Administration Schedule ,03 medical and health sciences ,Internal medicine ,medicine ,Humans ,Survival rate ,Transplantation ,business.industry ,medicine.disease ,Surgery ,Regimen ,Methotrexate ,Autologous stem cell transplant ,business ,Follow-Up Studies ,030215 immunology - Abstract
International audience; To evaluate the effect of rituximab in poor-prognosis patients with diffuse large B-cell lymphoma (DLBCL), a multicenter phase II trial combining rituximab with chemotherapy followed by high-dose therapy (HDT) with autologous stem cell transplant was conducted by the Groupe Ouest-Est des Leucémies et des Autres Maladies du Sang (GOELAMS). Patients were aged 18 to 60 years, with newly diagnosed CD20-expressing DLBCL, and at least 2 adverse risk factors as defined by the age-adjusted International Prognostic Index (aa-IPI). The treatment consisted of 2 courses of high-dose CHOP-like regimen on day 1 and 15 and 1 course of methotrexate and cytarabine on day 36. Four doses of rituximab (375 mg/m(2)) were infused on days 1, 15, 22, and 36. For patients who achieved at least a partial remission (PR), HDT followed by autologous stem cell transplant was performed on day 66. From April 2002 to May 2003, 42 patients were eligible. Half were high aa-IPI risk patients. Thirty-eight patients (90%) completed the treatment. Treatment-related mortality was 7% and no toxic death was related to rituximab. Complete response rate after the end of the full treatment was 67%. With a median follow-up of 66 months, event-free survival and overall survival rates were 55% and 74%, respectively. Median survival was not reached. First-line HDT with rituximab offers promising results for young adults with intermediate high or high aa-IPI high-grade lymphoma. Immediate and late toxicities were low. This treatment is being randomly compared prospectively with CHOP-14-rituximab in young adults with DLBCL (GOELAMS 075 trial). more...
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- 2010
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Catalog
3. Outcome is not improved by the use of alternating chemotherapy in elderly patients with aggressive lymphoma
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Georges Fillet, Christian Gisselbrecht, Eric Lepage, Raoul Herbrecht, Bertrand Coiffier, Hervé Tilly, Dominique Bordessoule, Brigitte Dupriez, André Bosly, Philippe Gaulard, C. Nouvel, Eric Deconninck, and Marine Divine more...
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Male ,medicine.medical_specialty ,Vindesine ,medicine.medical_treatment ,Population ,Aggressive lymphoma ,Drug Administration Schedule ,Bleomycin ,Internal medicine ,Antineoplastic Combined Chemotherapy Protocols ,Medicine ,Humans ,Ifosfamide ,Prospective Studies ,education ,Cyclophosphamide ,Aged ,Etoposide ,Alternating chemotherapy ,Chemotherapy ,education.field_of_study ,business.industry ,Lymphoma, Non-Hodgkin ,Remission Induction ,Hematology ,Middle Aged ,medicine.disease ,Survival Analysis ,Lymphoma ,Surgery ,Regimen ,Methotrexate ,Treatment Outcome ,Doxorubicin ,Toxicity ,Conventional chemotherapy ,Prednisone ,Female ,Mitoxantrone ,business - Abstract
INTRODUCTION: A prospective randomised study involving 810 elderly patients was conducted in an attempt to compare alternating chemotherapy with conventional first-line chemotherapy in aggressive non-Hodgkin's lymphoma in order to improve prognosis with an acceptable toxicity for elderly patients. PATIENTS AND METHODS: Patients included were 55-69 years old and had at least one adverse prognostic factor. Patients were treated either with ACVBP followed by consolidation (n = 396) or with an alternating regimen (n = 414). This regimen was an association of active drugs in NHL relapsing patients, alternating VIMMM with ACVBP for induction and alternation of VIM and ACVM in consolidation. Eight hundred and sixty-six patients were randomised. After histological review, 810 patients met the inclusion criteria: 396 in arm A, 414 in arm B. RESULTS: The complete response rate after induction was superior for conventional first-line therapy (58.5% vs 48%, P = 0.003) but at the end of treatment, the CR rate was not statistically different (52% vs 48%, P = 0.19). Conventional chemotherapy had a better five-year event-free survival than alternating regimen (33% (95% CI: 30-36%) vs 28% (95% CI: 26-30%), P = 0.0289) but overall survival was not statistically different (40% (CI 95% 38-42%) vs 36% (CI 95% 34-38%), P = 0.068). In this elderly high risk population, the toxicity was very high: 19% in arm A and 26% in arm B died during treatment. CONCLUSION: Alternating regimen did not improve outcome, was less efficient and more toxic. more...
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- 2000
4. Allogeneic Stem Cell Transplantation for Blast Crisis (BC) Chronic Myelogenous Leukemia (CML) In the Tyrosine Kinase Inhibitors (TKIs) Era. Analysis of Pre-Transplant Variables on Transplant Outcome. On Behalf of the Societe Française De Greffe De Moelle Et De Therapie Cellulaire and the French Group of CML
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Noel Milpied, Norbert Ifrah, Valérie Mialou, Eric Deconninck, Anne Sirvent, Mohamad Mohty, Thierry de Revel, Anne Huynh, Nicole Raus, Nathalie Fegueux, Franck E. Nicolini, Mauricette Michallet, Catherine Cordonnier, Didier Blaise, Gaelle Guillerm, Hervé Tilly, Jacques-Olivier Bay, Stephane Morisset, Bernard Rio, Jean-Hugues Dalle, Ibrahim Yakoub-Agha, Pierre Bordigoni, Karin Bilger, Agnes Buzyn, Gérard Socié, and Laurent Modolo more...
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Oncology ,Chemotherapy ,medicine.medical_specialty ,business.industry ,medicine.medical_treatment ,Immunology ,Cell Biology ,Hematology ,medicine.disease ,Biochemistry ,Chemotherapy regimen ,Dasatinib ,Transplantation ,Regimen ,Imatinib mesylate ,Internal medicine ,Medicine ,Cumulative incidence ,business ,medicine.drug ,Chronic myelogenous leukemia - Abstract
Abstract 2266 We conducted a national retrospective analysis on 63 patients (pts) with either myeloid or lymphoid BC CML who underwent a first allogeneic stem cell transplantation as consolidation therapy for BC, since 2000 in France and look at whether 1st and 2nd generation TKIs ±chemotherapy prior to transplant may impact on outcome. There were 46 males and 17 females, and the median age at transplant was 34 (range 3–63) years and the median delay between BC and transplant was 19.6 (2.3-113) months. Thirty six (57%) pts were in chronic phase (CP), 3 (5%) in accelerated and 24 (38%) in BC at CML diagnosis. Twenty three pts received 1 line of treatment, 26 pts 2 lines, and 14 pts 3 or more lines for CML treatment before BC. For BC treatment, 25/63 (39%) pts had chemotherapy without TKI and 29/63 (46%) had TKIs combined or not to chemotherapy (6 chemo+dasatinib, 4 chemo+imatinib, 8 dasatinib alone, 1 dasatinib and imatinib, 9 imatinib, 9 unknown). At transplant 35/63 (55%) were considered in 2nd CP and 28 (45%) still in BC. The majority of the pts had an identical sibling donor (42/63: 66%), 1 mismatched related, 7 matched unrelated, and 13 mismatched unrelated. Fifty-six (89%) pts had a standard conditioning regimen, 7 (11%) pts a RIC regimen and 39 (62%) had a TBI. The stem cell source was bone marrow in 33/63 (52%) pts, PBSC in 24/63 (38%) and cord blood for 6/63 (10%). Fourteen transplants were sex-mismatched (female donor for male recipient). The EBMT-Gratwohl score was low (1+2+3) for 35/63 (55%) pts, intermediate (4) for 14 pts and high (5) for 9 pts, (and 6) for 3 pts and undetermined for 2 pts. The median follow-up since transplant was 25 (range 0.43–109) months. The overall median time for neutrophil recovery (neutrophils > 0.5 109/l) was 20 days. Fourty-one (65%) pts had an aGVHD (29 grade i-II and 12 grade III-IV) with no statistical differences between stem cell sources (p=0.4 for cord vs BM and 0.58 for PBSC vs BM). The cumulative incidence of chronic GVHD (14 extensive, 10 limited) was 43% at latest follow-up, more frequent in RIC transplant. The cumulative incidence of CML relapse was 38% at 2 yrs and multivariate analysis demonstrated the significant impact on relapse of the status at transplant in favour of disease control prior to transplant [HR 2.22 (1-4.93, p=0.05] and unexpectedly, no impact of BC treatment with or without TKIs prior to transplant and of other variables. The median overall survival (OS) was 22 months (see Figure 1). The TRM was 33% at latest follow-up, and it was significantly negatively influenced by the EBMT score (p=0.0077 for scores ≥ 4), BC status at diagnosis (p=0.04). The OS was not improved when using standard conditioning regimens (p=ns), but was improved by disease status at transplant (2nd CP better than persistent BC, p=0.01) and transplant with cord blood and BM stem cell sources over PBSC (p=0.011). Multivariate analysis on OS detected as significant adverse prognosis factors EBMT score ≥5 (HR=4.63 EBMT 5, and 4.77 EBMT 6). The types of treatment of BC CML had no significant impact (with or without stratification on chemotherapy). The median progression-free survival (PFS) was 5.8 months (see Figure 2). The PFS was not significantly improved by standard conditioning regimens but again was improved by disease control prior to transplant (2nd CP better than persistent BC, p=0.001) and with cord blood and BM stem cell sources over PBSC (p=0.057). Multivariate analysis on PFS detected as significant adverse prognosis factors EBMT score ≥5 (HR=5.82 EBMT 5, and 3.82 EBMT 6), but again, the types of treatment of BC CML prior to transplant had no significant impact. In conclusion, this analysis suggests that OS and PFS rates are significantly improved when compared to figures from the pre-TKI era. The use of 1st or 2nd generation TKIs alone or combined to chemotherapy does not seem to influence transplant results. CML status and the EBMT score are the major factors that can significantly influence transplant outcome. Disclosures: No relevant conflicts of interest to declare. more...
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- 2010
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5. Updated Analysis of Allogeneic HSCT after RIC for Hematological Malignancies from the Société Française de Greffe de Moelle Osseuse et de Thérapie Cellulaire (SFGM-TC) Registry
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Quoc-Hung Le, Bernard Rio, Bernard Lioure, Marc Renaud, Mohamad Mohty, Nicole Raus, Jean-Michel Boiron, Pierre Bordigoni, Eric Deconninck, Didier Blaise, Mauricette Michallet, Jean-Henri Bourhis, Ibrahim Yackoub-Agha, Mohamad Sobh, Franck E. Nicolini, Noel Milpied, Helene Esperou, and Michel Attal more...
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medicine.medical_specialty ,business.industry ,Immunology ,Retrospective cohort study ,Cell Biology ,Hematology ,medicine.disease ,Biochemistry ,Gastroenterology ,Fludarabine ,Transplantation ,Regimen ,ABO blood group system ,Internal medicine ,Allogeneic hsct ,medicine ,business ,Progressive disease ,Busulfan ,medicine.drug - Abstract
This report updates a retrospective study from SFGM-TC registry concerning 1108 patients who underwent allogeneic hematopoeitic stem cell transplantation (HSCT) after reduced intensity conditioning (RIC) from HLA identical siblings (84%) and unrelated donors (16%) for hematological malignancies. At time of conditioning, 442 patients were in CR, 337 in PR, 107 in stable disease (SD) and 222 in progressive disease (PD). As conditioning, 255 patients received fludarabine and TBI (2 grays), 465 patients fludarabine, busulfan and ATG and 388 patients an other regimen. After transplant, 336 patients (30%) developed an acute GVHD ≥ grade II (grade II: 178, III: 80 and IV: 78). A chronic GVHD was present in 388 patients (35%) (185 limited and 203 extensive). With a median follow-up of 30 months, the 3 and 5-year probability of overall survival (OS) were 43.5% (40–47) and 32%(29–35) respectively and the 3 and 5-year probability of event-free survival (EFS) were 35%(31–39) and 28% (24.5–31) respectively. The TRM at 1 year, 2 years and 3 years was 15% (13–17), 18% (15.5–21) and 20% (17–23). A mixture model, gfcure with Splus statistical package determined the percentages of long-term survivors and its adequacy was verified graphically. The probability to be a long-survivor was 24% (17.5–32.5) (Fig.1) and to be a long event-free survivor was 23% (19–28) (Fig. 2). The multivariate analysis has tested recipient and donor age, disease status pre-transplant, number of transplants before RICT, HSC source, sex matching, HLA matching, CMV status and ABO compatibility. The only factor which had a significant impact on long-term survival after RICT was the disease status just prior conditioning: PR versus CR: HR: 3.63 [1.14–9.18] p Figure 1 Figure 1. Figure 2 Figure 2. more...
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- 2007
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6. Impact of HLA Allele Mismatch on the Outcome of Patients with Reduced-Intensity Allogeneic Haematopoietic Stem Cell Transplantation from Unrelated Donors: Analysis of 103 Patients of the French Registry
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Jean-Michel Boiron, Pierre Bordigoni, Marc Renaud, Colette Raffoux, Mauricette Michallet, Eric Deconninck, Jean-Paul Vernant, Anne Sirvent, Frédéric Garban, Zina Chir, Noel-Jean Milpied, Marie-Lorraine Balère-Appert, Nathalie Contentin, Gérard Socié, Didier Blaise, Andrea Toma, Agnes Buzyn, and Denis Guyotat more...
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medicine.medical_specialty ,Globulin ,biology ,business.industry ,medicine.medical_treatment ,Immunology ,Cell Biology ,Hematology ,Disease ,Hematopoietic stem cell transplantation ,Human leukocyte antigen ,Biochemistry ,Gastroenterology ,Transplantation ,Haematopoiesis ,immune system diseases ,hemic and lymphatic diseases ,Internal medicine ,biology.protein ,medicine ,Stem cell ,business ,HLA Allele Mismatch - Abstract
Reduced-intensity conditioning regimens (RIC) had become a classical strategy of allogeneic hematopoietic stem cell transplantation (HSCT) and many patients are now transplanted with unrelated donor. The aim of this restrospective study was to evaluate the impact of HLA mismatches between donor (D) and recipient (R) at the allelic level on survival after RIC. We analyzed 103 patients registered in France from Jan 1999 to Dec 2003 with a median age of 46 years (18–67). All patients had hematologic malignancies: AL (n=35), MM (n=18), CLL (n=5), NHL (n=11), HD (n=9), CML (n=12), MDS (n=9), and MPS (n=4). 39% of the patients were in an advanced phase of the disease at time of HSCT. Anti-thymocytes globulins (ATG) were part of the conditioning regimen for 77% of patients. The main source of stem cells was PBSC (n=65). Seventy-one D/R pairs (69%) were 10/10 HLA match at the allelic level. Mismatches concerned 5, 6, 15, 2 and 7 D/R pairs for HLA-A, -B, -C, -DRB1 and -DQB1, respectively. The results showed that 96% of patients engrafted. Acute GVHD grade II to IV and grade III/IV occurred in 46% and 19% of patients, respectively. The risk of developing cGvHD was 45% at 2 years. Overall survival (OS) was 42% at five years. Among the 47 patients alive, the median disease free survival (DFS) was 28 months. Among non-HLA parameters studied, the only factor associated with a good OS was the diagnosis of lymphoid disease (HD or NHL or CLL) (p=0.003). Recipient age more...
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- 2006
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7. Allogeneic Hematopoietic Stem Cell Transplantation Cures CLL: A Retrospective Analysis from the SFGM-TC Registry
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Philippe Colombat, Mauricette Michallet, Didier Blaise, Jean-Paul Vernant, Franck E. Nicolini, Bruno Cazin, Jean-Luc Harousseau, Eric Deconninck, and Quoc-Hung Le
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education.field_of_study ,medicine.medical_specialty ,Allogeneic transplantation ,business.industry ,medicine.medical_treatment ,Immunology ,Population ,Retrospective cohort study ,Cell Biology ,Hematology ,Hematopoietic stem cell transplantation ,medicine.disease ,Biochemistry ,Gastroenterology ,Surgery ,Transplantation ,Internal medicine ,medicine ,Autologous transplantation ,education ,business ,Survival analysis ,Progressive disease - Abstract
This retrospective study concerned 471 B-CLL patients registered in the SFGM-TC registry from Apr 1,984 to Feb 2,005, who underwent either autologous transplantation (n=313, 138 F and 175 M, median age = 54, 236 PBSC and 77 BM) or allogeneic transplantation (n=158, 78 F and 80 M, median age = 49, 76 PBSC, 81 BM and 1 cord blood cell transplant from 17 related and 141 unrelated donors). Among alloT patients, 50 were ABO incompatible and 70 sex-mismatched. The median interval diagnosis-transplantation was 32 months for autoT and 51 months for alloT. Just before conditioning 302 autoT and 143 alloT were evaluated for the disease status: 100 and 26 patients were in CR, 170 and 55 were in PR, 4 and 13 in stable disease (SD), 28 and 49 in progressive disease (PD) for autoT and alloT respectively. Among alloT patients, 73 received reduced intensity conditioning (RIC) and 85 standard conditioning (72 Cyt+TBI, 33 Fluda+TBI, 23 Fluda+Bu+ATG, 8 Cyt+Bu and 21 other). Before autoT the conditioning consisted of 224 Cyt+TBI, 45 BEAM and 44 other. After alloT, 71 patients developed an aGVHD ≥ grade II and 60 developed a cGVHD (25 limited and 35 extensive). The non-relapse mortality at 1 year was 29%. With a mean follow-up of 28 months for autoT and 40 months for alloT, the probabilities of 3-year, 5-year and 8-year overall survival were 80%, 66%, 45.5% after autoT and 52%, 48% and 35% after alloT respectively. An analysis aimed to determine the percentage of long-term survivors, or patients censored on the final plateau of survival curves was performed on alloT and autoT groups. A mixture model, gfcure with Splus statistical package determined the percentages of long-term survivors and its adequacy was verified graphically. The percentage of long-term survivors for the autoT group was 1.2%, with a mean survival length for uncured population of 160 months. Fig A shows that both curves were close and consequently shows good adequacy and the absence of a final plateau. The percentage of long-term survivors for alloT was 34.03% (figure1). Fig B shows rather good adequacy. The study of the impact of usual prognosis factors (age, time diagnosis-transplant, sex match, HLA match, CMV status, type of conditioning, BM or PBSC, ABO compatibility and disease status before transplantation) on the percentage of long-term survivors showed that only the status of disease at transplant had a significant impact: (CR vs SD or PD, HR: 0.11 [0.02–0.5] p=0.01 and PR vs SD or PD, HR: 0.30 [0.09–0.96] p=0.04). This study pointed out the possibility of curing B-CLL patients who responded to conventional chemotherapy with allogeneic transplantation rather than with autologous transplantation. Figure Figure Figure Figure more...
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- 2006
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8. Allogeneic Myelo-Ablative Stem Cell Transplant (SCT) as Salvage Therapy of Reduced-Intensity Conditioned (RIC) SCT: Toxicity and Outcome
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Mathieu Kuentz, Agnès Buzyn, Pierre Bordigoni, Loic Fouillard, Alois Gratwohl, Catherine Cordonnier, Sylvie François, Rose-Marie Hamladji, Jacques-Olivier Bay, Per Ljungman, Eric Deconninck, and Rodrigo Martino more...
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Oncology ,medicine.medical_specialty ,Thrombotic microangiopathy ,Cyclophosphamide ,business.industry ,medicine.medical_treatment ,Immunology ,Salvage therapy ,Cell Biology ,Hematology ,Hematopoietic stem cell transplantation ,Neutropenia ,medicine.disease ,Biochemistry ,Regimen ,surgical procedures, operative ,hemic and lymphatic diseases ,Cord blood ,Internal medicine ,Toxicity ,medicine ,business ,medicine.drug - Abstract
RIC regimens are mainly used for patients who cannot benefit from the myelo-ablative (MA) approach, due to age, previous SCT, or comorbidities, based on an expected early toxicity of MA regimen. Some centers may also choose the RIC strategy in young patients because they have no facilities for the management of prolonged neutropenia. The development of RIC has been so encouraging that programs now compare MA and RIC in patients who could tolerate both approaches. However, RIC may fail, and MA SCT be secondary considered. Objective: The goal of this retrospective survey was to assess the toxicity and outcome of MA after RIC SCT. Patients: 17 patients (14–63 y; 6 CML, 4 AML, 2 CLL, 2 myeloma, 1 NHL, 1 CMML, 1 myelodysplastic syndrome) received a MA SCT after RIC, for relapse (n=12), graft rejection (n=4), or in a planned program (n=1), from an HLA-id sibling (n=12), a familial mismatched donor (n=1), an unrelated donor (n=3) or a cord blood (n=1). The reason for initial RIC approach was age in 4, a research program in 6, comorbidities in 3, and previous autologous SCT in 4 patients. RIC included Fludarabin (Flu)-Busulfan (BU) in 8, Flu-2Gy irradiation in 4, Cyclophosphamide (CPM)-antithymocyte globulin (ATG) in 1, and various Flu- regimens in 4. One patient had 2 consecutive RIC SCTs before MA SCT. The median delay between RIC and MA SCT was 9 months (range: 2.5–36 months). The same donor was used for the 1st and 2nd SCT in 12/17 cases. The MA transplant was conditioned with BU-CY (±VP16) in 9, Cyclo-TBI in 4, and other regimens in 4 patients. The median follow-up after MA SCT was 9 months Results: After the MA transplant, 1 patient developed veno-occlusive disease, 2 developed interstitial pneumonia. Five patients died from relapse between 8 and 21 mo after the MA SCT. Seven (41%) died from transplant-related causes at a median of 8 months (GVHD:3; infection:1; multi-organ failure:1; thrombotic microangiopathy:1; EBV proliferative disease:1). 5/17 (29.5%) patients are alive and well 4.5 to 26 months after MA transplant. Three of them have extensive chronic GVHD while they did not develop any GVHD after RIC. The delay between the 2 transplants did not influence the outcome. Conclusion: This survey shows that MA after RIC SCT is feasible, and considering that most of these patients have been initially eligible for RIC because of their age or comorbidities, MA SCT had an acceptable toxicity. It may be considered for patients who relapsed or rejected after RIC transplant. more...
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- 2005
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9. Front-Line High-Dose Chemotherapy (HDT) Combined with Rituximab for Adults with Aggressive Large B-Cell Lymphoma (DLBCL) : Goelams 074 Trial
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Olivier Tournilhac, Eric Legouffe, Eric Deconninck, Philippe Colombat, Thierry Lamy, Christine Le Maignan, J. Dugay, Hervé Maisonneuve, Jean-François Ramée, Philippe Casassus, Noel-Jean Milpied, Remy Gressin, and Vincent Delwail more...
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Oncology ,medicine.medical_specialty ,business.industry ,Immunology ,Cell Biology ,Hematology ,CHOP ,medicine.disease ,Biochemistry ,Chemotherapy regimen ,Surgery ,Lymphoma ,Transplantation ,Regimen ,Autologous stem-cell transplantation ,hemic and lymphatic diseases ,Internal medicine ,medicine ,Rituximab ,Methotrexate ,business ,medicine.drug - Abstract
Background: The beneficial effect of adding rituximab to CHOP has been shown for elderly patients with DLBCL (Coiffier et al, N.E.J.M 2002). We have shown that HDT with autologous stem cell transplantation is superior to CHOP in young adults with DLCL ( Milpied et al GOELAMS 072 trial, N.E.J.M 2004). The feasibility of adding rituximab to front-line HDT remains to be established. Methods: A prospective pilot trial was proposed to patients with DLBCL, with intermediate-high or high adjusted IPI, up to the age of 60 y.o. This program consisted of 2 courses of high-dose CHOP-like regimen, 15 days apart, with rituximab (375/mg/m2) on day 1 of each course, followed by rituximab on d 22, harvest of G-CSF mobilised peripheral blood stem cells on d 28,29, then rituximab on d 36 followed by a course of high-dose methotrexate with cytarabin. For patients who achieved at least a PR after these 3 courses, a BEAM regimen started on d 66 to 80 followed by the infusion of stem cells. Results: Between 04/2002 and 05/2003, 42 pts gave their informed consent and were included in that trial. Median age was 50 y.o (18–60 y.o), 23 had WHO PS ≥ 2, the LDH level was >N in 41 pts and 38 had stage III or IV disease. The age-adjusted IPI was intermediate-high in 23 and high in 19 pts. The program was completed in 30 pts (71%), 3 pts died of toxicity before the BEAM regimen, 8 pts failed to achieve at least a PR after the first 3 courses and 1 refused the autologous transplant. On an intent-to-treat basis, the response rate at the end of the treatment was CR/Cru=64%, PR=7%, less than PR or progression= 22% and toxic death=7%. No toxic death was directly attributable to the addition of rituximab. With a median FU of 19 m, the KM 2y probability of OS and EFS are 79% and 59% respectively, these figures compare to those achieved without rituximab in the previous trial as shown on the table: Conclusion : The addition of 4 doses of rituximab to this HDT program is feasible with no unexpected toxicity, allows the harvesting of sufficient numbers of stem cells to support an autologous transplant with a BEAM regimen in responding patients. This treatment is now being randomly prospectively compared with CHOP-14-rituximab in youg adults with DLBCL (Goelams 075 trial).Supported in part by Roche which kindly provided rituximab for that trial and by DRC Nantes programme N°:02/2N 2002. GOELAMS 072 (IPI 2 only) GOELAMS 074 (IPI 2–3) 2y OS 80% 79% 2y EFS 60% 59% more...
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- 2004
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10. Front-line high-dose chemotherapy (HDT) combined with rituximab for adults with aggressive large B cell lymphoma (DLBCL). A pilot study by the GOELAMS
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T. Lamy, Eric Deconninck, Remy Gressin, Noel-Jean Milpied, J. Dugay, C. Le Maignan, Vincent Delwail, O. Tournilhac, Philippe Casassus, and Eric Legouffe
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Oncology ,Cancer Research ,medicine.medical_specialty ,business.industry ,CHOP ,medicine.disease ,Surgery ,Regimen ,Autologous stem-cell transplantation ,immune system diseases ,hemic and lymphatic diseases ,Internal medicine ,medicine ,Cytarabine ,Rituximab ,Methotrexate ,Stem cell ,business ,B-cell lymphoma ,medicine.drug - Abstract
6662 Background: The beneficial effect of adding rituximab to CHOP has been shown for elderly patients with DLBCL (Coiffier et al NEJM 2002). We have shown that HDT with autologous stem cell transplantation is superior to CHOP in young adults with DLCL (Milpied et al NEJM in press). The feasibility of adding rituximab to front-line HDT remains to be established. Methods: A prospective pilot trial was proposed to patients with DLBCL, with intermediate-high or high age-adjusted IPI, up to the age of 60 y.o. This program consisted of 2 courses of high-dose CHOP-like regimen, 15 days apart, with rituximab (375 mg/ m2) on d1 of each course, followed by rituximab on d 22, harvest of peripheral blood stem cells (G-CSF mobilized) on days 28,29, then rituximab on d 36 followed by a course of high-dose methotrexate with cytarabine and by a BEAM regimen starting on d 66 to 80, followed by the infusion of stem cells. Results: Between 04/2002 and 05/2003, 41 consecutive patients gave their informed consent and were in... more...
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- 2004
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11. Consolidation Anti-CD22 Fractionated Radioimmunotherapy with 90Y Epratuzumab Tetraxetan Following R-CHOP In Elderly DLBCL Patients
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Thierry Lamy, William A. Wegener, Caroline Bodet-Milin, Jean-François Chatal, Françoise Kraeber-Bodéré, Jean-Philippe Vuillez, Nadine Morineau, Hervé Maisonneuve, Emmanuel Gyan, Alain Faivre-Chauvet, Noel Milpied, Pierre Soubeyran, Anne Moreau, Anne-Laure Cazeau, Philippe Moreau, Eric Deconninck, Remy Gressin, Steven Le Gouill, Jean-Luc Harousseau, Etienne Garin, Thomas Gastinne, Amandine Pallardy, Charles Foussard, Olivier Tournilhac, and David M. Goldenberg more...
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medicine.medical_specialty ,business.industry ,medicine.medical_treatment ,Immunology ,Follicular lymphoma ,Cell Biology ,Hematology ,Neutropenia ,medicine.disease ,Biochemistry ,Chemotherapy regimen ,Gastroenterology ,Internal medicine ,Radioimmunotherapy ,medicine ,Mucositis ,business ,Epratuzumab ,Progressive disease ,Febrile neutropenia ,medicine.drug - Abstract
Abstract 2875 Background: Radioimmunotherapy (RIT) is under study as a consolidation treatment after chemotherapy induction in follicular lymphoma patients. This approach also appears interesting in diffuse large B-cell lymphoma (DLBCL) patients >60 years, who are not candidates for bone marrow transplantation. 90Y-epratuzumab tetraxetan (Immunomedics, Inc.) is a radiolabeled humanized anti-CD22 antibody that has been used for a fractionated RIT, showing high rates of durable complete responses with manageable hematologic toxicity in previously-treated indolent and aggressive non-Hodgkin lymphoma (NHL) patients (Morschhauser et al., J Clin Oncol. 2010;28(23);3709-16). A French phase II trial sponsored by the GOELAMS group is ongoing, assessing fractionated RIT using 90Y-epratuzumab tetraxetan as a consolidation therapy after first-line chemotherapy in disseminated DLBCL patients >60 years. The protocol has been designed to include 75 patients; 64 patients have been already enrolled. We report the initial results, in particular safety data, on the first 29 available patients. Design and Method: From October 2008 to November 2009, 29 untreated DLCBL patients >60 years were studied in several French institutions with an initial course of six cycles of R-CHOP14 followed 8 weeks later by two weekly infusions of 90Y-epratuzumab tetraxetan (15 mCi/m2 [555 MBq/m2]) 7 days apart. Hematologic and non-hematologic toxicities were evaluated using NCI-CTC v.3.0. Treatment responses were classified according to the 1999 International Workshop for Response Criteria for NHL. Results: Twenty-six patients underwent the entire course of R-CHOP and 23 received the 2 weekly RIT injections. Following R-CHOP, grade 3–4 neutropenia was observed in 20 patients (68.9%) and grade 3–4 thrombocytopenia in 4 (13.7%). During RIT infusions, 4 patients showed transient change of pulse or blood pressure, with 2 attributed to vasovagal reactions. RIT toxicity included grade 3–4 hematologic toxicity in 18 of 23 patients (78.3%); the most common grade > 3 toxicities were neutropenia (N=18, 78.3%) and thrombocytopenia (N=17, 73.9%). Serious febrile neutropenia was observed in 4 cases (13.8%) after R-CHOP and in 2 patients (8.7%) following RIT. Compared to R-CHOP, RIT non-hematologic toxicity was uncommon; moderate or severe gastrointestinal toxicity was observed in 10 patients (34.5%) after R-CHOP and in 2 (8.7%) following RIT; moderate or severe infection in 9 patients (31.0%) after R-CHOP and in 1 (4.3%) after RIT; and moderate or severe mucositis in 10 (34.4%) patients following R-CHOP, while no patient had mucositis after RIT. Following RIT, red cells and/or platelets transfusions were given to 12 patients (52,2%). Following R-CHOP, 10 of the 25 patients (40.0%) achieved a complete response (CR) or unconfirmed CR (CRu), 13 patients (52.0%) had a partial response (PR) and 2 patients (8.0%) had a stable disease. Six weeks after RIT, 13 patients (56.5%) achieved a CR or CRu, 9 patients (39.1%) had PRs, and 1 patient (4.3%) had progressive disease. Four of 13 patients (30.7%) who achieved less than a CR or CRu with R-CHOP improved their remission status 6 weeks after RIT. Conclusion: These preliminary results indicate the feasibility and safety of fractionated RIT with 90Y-epratuzumab as a consolidation therapy for elderly DLBCL patients. Additional data will be presented at the time of the communication. Disclosures: Off Label Use: monoclonal antibody epratuzumab labeled with yttrium 90 in phase II clinical trial. Wegener:Immunomedics, Inc.: Employment, shareholders. Goldenberg:Immunomedics, Inc.: Employment, shareholders. more...
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