Agnès Buzyn

Université René Descartes - Paris 5, Lutetia Parisorum, Île-de-France, France

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Publications (168)

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    [Show abstract] [Hide abstract] ABSTRACT: As indication of allograft (alloSCT) for multiple myeloma (MM) widened in the recent years, thanks to the development of reduced intensity conditionings (RIC), it is still unclear if myeloablative conditionings remain appropriate. This study compares retrospectively outcomes of patients undergoing either RIC or MAC regimens for MM. Based on the SFGM-TC registry, we included 446 MM patients receiving alloSCT between 1999 and 2009 for whom a minimal data set was available. Median follow-up for the entire cohort was 33.6 months [0-164.5]. RIC and MAC populations were different regarding age (53.5 vs. 47.1 years respectively), number of prior autoSCT (93.2 vs. 79.6 % had at least 2 autoSCT), and stem cell source (90.2 vs. 61.2 % received peripheral blood). For RIC and MAC populations respectively, the non-relapse mortality at 2 years was 24.6 % and 22.4 %; progression free survival 35.5 % and 51.1 %; and overall survival 59.5 % and 66.7 % (p = ns). These outcomes were not affected by conditioning intensity either on univariate nor multivariate analysis. Despite some limitations in the study design, these results incite to consider that MAC has to remain a valuable option in alloSCT for MM, especially for young and less treated patient with no comorbidity. The constant progress in induction treatments of MM and supportive care after alloSCT could improve these results in the near future. Copyright © 2015 American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.
    Full-text Article · Apr 2015 · Biology of blood and marrow transplantation: journal of the American Society for Blood and Marrow Transplantation
  • [Show abstract] [Hide abstract] ABSTRACT: Rationale Systemic steroids are the standard treatment for bronchiolitis obliterans syndrome (BOS) after allogeneic hematopoietic stem cell transplantation (HSCT), despite their poor efficacy and disabling side effects. Objectives To evaluate the effectiveness and tolerance of budesonide/formoterol as an alternative treatment for BOS following HSCT. Methods In this randomized, double-blind, placebo-controlled study, we randomly assigned 32 HSCT recipients with mild/severe BOS to receive budesonide/formoterol or placebo for six months. The primary outcome was the change in the FEV1 after one month of treatment (M1) compared with the baseline value. Patients were unblinded at M1 if there was no improvement in the FEV1. Those who had initially received the placebo were switched to budesonide/formoterol. Intention-to-treat analysis was performed to assess the primary outcome. Additional analyses took scheduled treatment contamination into account. Measurements and main results At M1, the median FEV1 increased by 260 mL in the budesonide/formoterol arm compared with 5 mL in the placebo arm (p=0.012). The median increases in the FEV1 at M1 relative to the baseline value for the treated and placebo groups were 13% and 0%, respectively (p=0.019). Twenty-five patients received budesonide/formoterol during the study. The median difference in the FEV1 between the baseline and after one month of treatment for these patients was +240 mL (p=0.0001). The effect of budesonide/formoterol on the FEV1 was maintained in the 13 patients who completed six months of treatment. Conclusions Budesonide/formoterol administration led to a significant improvement in the FEV1 in patients with mild/severe BOS after allogeneic HSCT. Clinical trial registration available at, ID NCT00624754.
    Article · Apr 2015 · American Journal of Respiratory and Critical Care Medicine
  • [Show abstract] [Hide abstract] ABSTRACT: Intensive care unit (ICU) admission is associated with high mortality in allogeneic hematopoietic stem cell transplant (HSCT) recipients. Whether mortality has decreased recently is unknown. The 497 adult allogeneic HSCT recipients admitted to three ICUs between 1997 and 2011 were evaluated retrospectively. Two hundred and nine patients admitted between 1997 and 2003 were compared with the 288 patients admitted from 2004 to 2011. Factors associated with 90-day mortality were identified. The recent cohort was characterized by older age, lower conditioning intensity, and greater use of peripheral blood or unrelated-donor graft. In the recent cohort, ICU was used more often for patients in hematological remission (67% vs 44%; P<0.0001) and without GVHD (73% vs 48%; P<0.0001) or invasive fungal infection (85% vs 73%; P=0.0003) despite a stable admission rate (21.7%). These changes were associated with significantly better 90-day survival (49% vs 31%). Independent predictors of hospital mortality were GVHD, mechanical ventilation (MV) and renal replacement therapy (RRT). Among patients who required MV or RRT, survival was 29% and 18%, respectively, but dropped to 18% and 6% in those with GVHD. The use of ICU admission has changed and translated into improved survival, but advanced life support in patients with GVHD usually provides no benefits.Bone Marrow Transplantation advance online publication, 23 March 2015; doi:10.1038/bmt.2015.55.
    Article · Mar 2015 · Bone marrow transplantation
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    Dataset: JI
    Zhi-Tao Yang · Marc Lecuit · Felipe Suarez · [...] · Olivier Lortholary
    Full-text Dataset · Jan 2015
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    [Show abstract] [Hide abstract] ABSTRACT: Background The purpose of this study was to describe the natural history of severe congenital neutropenia (SCN) in 14 patients with G6PC3 mutations and enrolled in the French SCN registry.Methods Among 605 patients included in the French SCN registry, we identified 8 pedigrees that included 14 patients with autosomal recessive G6PC3 mutations.ResultsMedian age at the last visit was 22.4 years. All patients had developed various comordibities, including prominent veins (n¿=¿12), cardiac malformations (n¿=¿12), intellectual disability (n¿=¿7), and myopathic syndrome with recurrent painful cramps (n¿=¿1). Three patients developed Crohn¿s disease, and five had chronic diarrhea with steatorrhea. Neutropenia was profound (<0.5¿×¿109/l) in almost all cases at diagnosis and could marginally fluctuate. The bone marrow smears exhibited mild late-stage granulopoeitic defects. One patient developed myelodysplasia followed by acute myelogenous leukemia with translocation (18, 21) at age 14 years, cured by chemotherapy and hematopoietic stem cell transplantation. Four deaths occurred, including one from sepsis at age 5, one from pulmonary late-stage insufficiency at age 19, and two from sudden death, both at age 30 years. A new homozygous mutation (c.249G¿>¿A /p.Trp83*) was detected in one pedigree.Conclusions Severe congenital neutropenia with autosomal recessive G6PC3 mutations is associated with considerable clinical heterogeneity. This series includes the first described case of malignancy in this neutropenia.
    Full-text Article · Dec 2014 · Orphanet Journal of Rare Diseases
  • [Show abstract] [Hide abstract] ABSTRACT: A prospective phase II multicentric trial was performed to obtain less than 25% non-relapse mortality (NRM) after unrelated cord blood transplantation (UCBT) for adults with acute myeloid leukemia (AML) using reduced intensity conditioning regimen (RIC) consisting of total body irradiation (TBI 2Gy), cyclophosphamide (50mg/kg) and fludarabine (200mg/m2) (TCF). From 2007 to 2009, 79 UCBT recipients were enrolled. Patients transplanted in first complete remission (CR1) (n=48) had a higher frequency of unfavorable cytogenetics, secondary AML and greater number of induction courses of chemotherapy to achieve CR1 compared to the others. The median infused total nucleated cells (TNC) was 3.4 x107/kg; 60% received double UCBT; 77% were HLA mismatched (4/6) and 40% had major ABO-incompatibility. Cumulative incidence (CI) of neutrophil recovery at day-60 was 87% and CI of 100-day acute-GVHD (II-IV) was 50%. At 2-years, CI of NRM and relapse incidence were 20% and 46%, respectively. In a multivariate analysis, major ABO incompatibility (p=0.001) and TNC (<3.4x107/kg; p=0.001) were associated with increased NRM and use of 2 or more induction courses to obtain CR1 with increased relapse incidence (p=0.04). Leukemia-free survival (LFS) at 2-years was 35%, and the only factor associated with decreased LFS was secondary AML (p=0.04). In conclusion, despite the decreased NRM observed, other RIC regimens with higher myelosuppression should be evaluated to decrease relapse in high risk AML. (EUDRACT 2006-005901-67). Copyright © 2014 American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.
    Article · Nov 2014 · Biology of blood and marrow transplantation: journal of the American Society for Blood and Marrow Transplantation
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    [Show abstract] [Hide abstract] ABSTRACT: With intensified pediatric-like therapy and genetic disease dissection, the field of adult acute lymphoblastic leukemia (ALL) has evolved recently. In this new context, we aimed to reassess the value of conventional risk factors with regard to new genetic alterations and early response to therapy, as assessed by Ig/TCR minimal residual disease (MRD) levels. The study was performed in 423 younger adults with Philadelphia chromosome-negative ALL in first remission (265 B-cell precursor [BCP] and 158 T-cell ALL), with cumulative incidence of relapse (CIR) as primary endpoint. In addition to conventional risk factors, the most frequent currently available genetic alterations were included in the analysis. A higher specific hazard of relapse was independently associated with post-induction MRD level ≥ 10(-4) and unfavorable genetic characteristics (i.e. MLL gene rearrangement or focal IKZF1 gene deletion in BCP-ALL; and no NOTCH1/FBXW7 mutation and/or N/K-RAS mutation and/or PTEN gene alteration in T-ALL). These two factors allowed definition of a new risk classification, which is strongly associated with higher CIR and shorter relapse-free and overall survival. These results indicate that genetic abnormalities are important predictors of outcome in adult ALL, not fully recapitulated by early response to therapy. Patients included in this study were treated in the multicenter GRAALL-2003 and 2005 trials. Both trials were registered at (GRAALL-2003, NCT00222027; GRAALL-2005, NCT00327678).
    Full-text Article · Apr 2014 · Blood
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    [Show abstract] [Hide abstract] ABSTRACT: The Group for Research in Adult Acute Lymphoblastic Leukemia (GRAALL) recently reported a significantly better outcome in T-cell acute lymphoblastic leukemia (T-ALL) harboring NOTCH1 and/or FBXW7 (N/F) mutations compared with unmutated T-ALL. Despite this, one third of patients with N/F-mutated T-ALL experienced relapse. In a series of 212 adult T-ALLs included in the multicenter randomized GRAALL-2003 and -2005 trials, we searched for additional N/K-RAS mutations and PTEN defects (mutations and gene deletion). N/F mutations were identified in 143 (67%) of 212 patients, and lack of N/F mutation was confirmed to be associated with a poor prognosis. K-RAS, N-RAS, and PTEN mutations/deletions were identified in three (1.6%) of 191, 17 (8.9%) of 191, and 21 (12%) of 175 patients, respectively. The favorable prognostic significance of N/F mutations was restricted to patients without RAS/PTEN abnormalities. These observations led us to propose a new T-ALL oncogenetic classifier defining low-risk patients as those with N/F mutation but no RAS/PTEN mutation (97 of 189 patients; 51%) and all other patients (49%; including 13% with N/F and RAS/PTEN mutations) as high-risk patients. In multivariable analysis, this oncogenetic classifier remained the only significant prognostic covariate (event-free survival: hazard ratio [HR], 3.2; 95% CI, 1.9 to 5.15; P < .001; and overall survival: HR, 3.2; 95% CI, 1.9 to 5.6; P < .001). These data demonstrate that the presence of N/F mutations in the absence of RAS or PTEN abnormalities predicts good outcome in almost 50% of adult T-ALL. Conversely, the absence of N/F or presence of RAS/PTEN alterations identifies the remaining cohort of patients with poor prognosis.
    Full-text Article · Oct 2013 · Journal of Clinical Oncology
  • [Show abstract] [Hide abstract] ABSTRACT: Allogeneic hematopoietic stem cell transplantation (HSCT) is a curative treatment for many hematological malignancies for which umbilical cord blood (UCB) represents an alternative source of HSC. In order to overcome the low cellularity of one UCB unit, double UCBT (dUCBT) has been developed in adults. We have analyzed the outcome of 136 patients who underwent dUCBT reported to the SFGM-TC registry between 2005 and 2007. Forty-six patients received myeloablative and 90 reduced intensity conditioning regimens. There were 84 leukemias, 17 NHL, 11 myelomas and 24 other hematological malignancies. At transplantation, 40 (29%) patients were in CR1. At day 60 after transplantation, the cumulative incidence of neutrophil recovery was 91%. We observed one UCB unit domination in 88% of cases. The cumulative incidence of day 100 aGVHD, cGVHD, TRM and relapse at 2 years were 36%, 23%, 27% and 28% respectively. After a median follow-up of 49.5 months, the 3 years probabilities of overall and progression-free survival were 41% and 35% respectively with a significant OS advantage when male cord engrafted male recipients. We obtained a long term plateau among patients in CR1 which makes dUCBT a promising treatment strategy for these patients.
    Article · Jul 2013 · Experimental hematology
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    Full-text Article · Jan 2013
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    [Show abstract] [Hide abstract] ABSTRACT: To assess the role of hematopoietic SCT (HSCT) in adult ALL patients with central nervous system involvement at diagnosis, we retrospectively analyzed 90 patients who underwent autologous HSCT (auto-HSCT group; n=27) or allogeneic HSCT (allo-HSCT group; n=63) and reported to the Société Française de Greffe de Moelle et de Thérapie Cellulaire registry between 1994 and 2008. At the time of transplantation, 67 patients (74%) were in first CR, 15 (17%) in CR2 and 8 (9%) with progressive disease. The 5-year probabilities of overall survival (OS) and disease-free survival (DFS) were 52% and 46% for the allo-HSCT and 37% and 33% for the auto-HSCT groups, respectively (P=NS). The TRM at 5 years was 29.8% for the allo-HSCT group and 3.7% for the auto-HSCT group. Using univariate analysis, a time for transplantation of <12 months, the remission status at transplantation, the use of high-dose TBI and the number of the transplant were all determined to be prognostic factors for improved DFS and OS probabilities. Using multivariate analysis, we demonstrated that both the use of high-dose TBI and the remission status had a favorable impact on OS. Although the DFS and OS were better in the allo-HSCT group, the differences were not statistically significant.Bone Marrow Transplantation advance online publication, 19 November 2012; doi:10.1038/bmt.2012.213.
    Full-text Article · Nov 2012 · Bone marrow transplantation
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    [Show abstract] [Hide abstract] ABSTRACT: Invariant natural killer T (iNKT) cells can experimentally dissociate GVL from graft-versus-host-disease (GVHD). Their role in human conventional allogeneic hematopoietic stem cell transplantation (HSCT) is unknown. Here, we analyzed the post-HSCT recovery of iNKT cells in 71 adult allografted patients. Results were compared with conventional T- and NK-cell recovery and correlated to the occurrence of GVHD, relapse, and survival. We observed that posttransplantation iNKT cells, likely of donor origin, recovered independently of T and NK cells in the first 90 days after HSCT and reached greater levels in recipient younger than 45 years (P = .003) and after a reduced-intensity conditioning regimen (P = .03). Low posttransplantation iNKT/T ratios (ie, < 10(-3)) were an independent factor associated with the occurrence of acute GVHD (aGVHD; P = .001). Inversely, reaching iNKT/T ratios > 10(-3) before day 90 was associated with reduced nonrelapse mortality (P = .009) without increased risk of relapse and appeared as an independent predictive factor of an improved overall survival (P = .028). Furthermore, an iNKT/T ratio on day 15 > 0.58 × 10(-3) was associated with a 94% risk reduction of aGVHD. These findings provide a proof of concept that early postallogeneic HSCT iNKT cell recovery can predict the occurrence of aGVHD and an improved overall survival.
    Full-text Article · Jun 2012 · Blood
  • Conference Paper · Apr 2012
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    [Show abstract] [Hide abstract] ABSTRACT: Background: Despite therapeutic approach that combines rituximab-containing chemotherapy, followed or not by autologous stem cell transplantation (auto-SCT), mantle cell lymphoma (MCL) patients experience relapses. Reduced-intensity conditioning allogeneic stem cell transplantation (RIC-allo-SCT) at time of relapse may represent an attractive strategy. Patients and methods: We report a multicenter retrospective analysis. Seventy MCL patients underwent RIC-allo-SCT in 12 centers. Results: Median age at transplantation was 56 years and median time from diagnosis to transplantation was 44 months. The median number of previous therapies was 2 (range, 1-5) including autologous transplantation in 47 cases. At time of transplantation, 35 patients were in complete remission, 20 were in partial response and 15 in stable disease or progressive disease. The median follow-up for living patients was 24 months. The 2-year event-free survival (EFS) and overall survival (OS) rates were 50% and 53%, respectively. The 1- and 2-year transplant-related mortality rates were 22% and 32%, respectively. The statistical analysis demonstrated that disease status at transplantation was the only parameter influencing EFS and OS. Conclusions: These results suggest that RIC-allo-SCT may be an effective therapy in MCL patients with a chemo-sensitive disease at time of transplantation, irrespective of the number of lines of prior therapy. Studies are warranted to investigate the best type of RIC regimen.
    Full-text Article · Mar 2012 · Annals of Oncology
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    [Show abstract] [Hide abstract] ABSTRACT: Despite recent progress in the understanding of acute lymphoblastic leukemia (T-ALL) oncogenesis, few markers are sufficiently frequent in large subgroups to allow their use in therapeutic stratification. Low ERG and BAALC expression (E/B(low)) and NOTCH1/FBXW7 (N/F) mutations have been proposed as powerful prognostic markers in large cohorts of adult T-ALL. We therefore compared the predictive prognostic value of N/F mutations versus E/B(low) in 232 adult T-ALLs enrolled in the LALA-94 and Group for Research on Adult Acute Lymphoblastic Leukemia (GRAALL) protocols. The outcome of T-ALLs treated in the pediatric-inspired GRAALL trials was significantly superior to the LALA-94 trial. Overall, 43% and 69% of adult T-ALL patients were classified as E/B(low) and N/F mutated, respectively. Strikingly, the good prognosis of N/F mutated patients was stronger in more intensively treated, pediatric-inspired GRAALL patients. The E/B expression level did not influence the prognosis in any subgroup. N/F mutation status and the GRAALL trial were the only 2 independent factors that correlated with longer overall survival by multivariate analysis. This study demonstrates that the N/F mutational status and treatment protocol are major outcome determinants for adults with T-ALL, the benefit of pediatric inspired protocols being essentially restricted to the N/F mutated subgroup.
    Full-text Article · Aug 2011 · Blood
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    [Show abstract] [Hide abstract] ABSTRACT: This retrospective multicenter report assessed the outcome of 600 patients with hematologic diseases older than 60 years who received reduced-intensity conditioning (RIC) allogeneic hematopoietic stem cell transplantation (allo-HSCT), with the specific aim to compare outcomes of patients between 60 and 65 years old (N = 493) with those older than 65 years (N = 107). Except for donor age, there were no significant differences between the groups regarding patients, diseases, and allo-HSCT characteristics. At time of RIC allo-HSCT, 276 patients (46%) were in complete remission. With a median follow-up of 22.8 and 23.7 months in the younger and the older groups, respectively, 2-year relapse, nonrelapse mortality, disease-free survival, and overall survival rates were similar in both groups (29.6% vs. 20.4%; 29.9% vs. 34.6%; 40.6% vs. 46.7%; 49.2% vs. 50.2%, respectively; P = NS for all comparisons). In a Cox multivariate analysis, after adjustment for disease and transplant factors, age per se was not an adverse factor for survival (relative risk = 1.08; 95% confidence interval, 0.81-1.44, P = .62). We conclude that in selected patients, RIC allo-HSCT could be offered to patients over 65 years old.
    Full-text Article · Jul 2011 · Biology of blood and marrow transplantation: journal of the American Society for Blood and Marrow Transplantation
  • [Show abstract] [Hide abstract] ABSTRACT: The purpose of this paper is to describe the outcome of patients who underwent double allogeneic hematopoietic stem cell transplantation (AHSCT) with reduced-intensity conditioning regimens (RIC). Forty-five patients who received double RIC-AHSCT between 1997 and 2006 were retrospectively studied. The predominant diagnosis was acute myeloid leukemia (AML) (n = 17). Other diagnoses were aplasic anemia (AA) (n = 5), myelodysplasic disorder (n = 5), acute lymphoblastic leukemia (ALL) (n = 4), chronic myelomonocytic leukemia (CML) (n = 3), myeloma (n = 3), non-Hodgkin lymphoma (NHL) (n = 3), chronic lymphocytic leukemia (CLL) (n = 2), Hodgkin's disease (HD) (n = 2), and chronic myelomonocytic leukemia (n = 1). Main indications for RIC-AHSCT 2 were relapse (n = 25, 56%) and early (n = 8, 18%) or late (n = 12, 26%) graft failure. Median delays to reach a neutrophil count of 0.5 × 10(9)/L and platelet counts of 50 × 10(9)/L were significantly smaller after the second AHSCT. Among 25 patients who relapsed after RIC-AHSCT 1, 14 patients (56%) presented a response improvement after RIC-AHSCT 2. In this group, 9 patients sustained a complete response and 5 patients a partial response. Moreover, among the 20 patients who had early or late graft failure following RIC-AHSCT 1, 9 (45%) finally reached an engraftment. Disease-free survival (DFS) was significantly improved after RIC-AHSCT 2. Thirteen patients (28%) died of transplant-related mortality (TRM) at a median delay of 69 days (range: 0-451) after RIC-AHSCT 2. Double RIC-AHSCT is a feasible procedure that allows a response or engraftment not observed after RIC-AHSCT 1. The main indication is relapse. However, TRM remains high.
    Article · Jul 2011 · Biology of blood and marrow transplantation: journal of the American Society for Blood and Marrow Transplantation
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    [Show abstract] [Hide abstract] ABSTRACT: The impact of cytogenetic abnormalities in multiple myeloma after allogeneic stem cell transplantation has not been clearly defined. This study examines whether allogeneic stem cell transplantation could be of benefit for myeloma patients with high-risk cytogenetic abnormalities. This is a retrospective multicenter analysis of the registry of the Société Française de Greffe de Moelle et de Thérapie Cellulaire, including 143 myeloma patients transplanted between 1999 and 2008. The incidences of cytogenetic abnormalities were 59% for del(13q), 25% for t(4;14), 25% for del(17p) and 4% for t(14;16). When comparing the population carrying an abnormality to that without the same abnormality, no significant difference was found in progression-free survival, overall survival or progression rate. Patients were grouped according to the presence of any of the poor prognosis cytogenetic abnormalities t(4;14), del(17p) or t(14;16) (n=53) or their absence (n=32). No difference in outcomes was observed between these two groups: the 3-year progression-free survival, overall survival and progression rates were 30% versus 17% (P=0.9), 45% versus 39% (P=0.8) and 53% versus 75% (P=0.9), respectively. These data indicate that allogeneic stem cell transplantation could potentially be of benefit to high-risk myeloma patients.
    Full-text Article · Jun 2011 · Haematologica
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    E Jantunen · C Canals · M Attal · [...] · A Sureda
    [Show abstract] [Hide abstract] ABSTRACT: Limited experience is available on the feasibility and efficacy of autologous stem-cell transplantation (ASCT) in patients with mantle cell lymphoma (MCL) beyond 65 years. We analysed 712 patients with MCL treated with ASCT from 2000 to 2007 and reported to the European Group for Blood and Marrow Transplantation registry. Patients>65 years were compared with patients<65 years for the end points non-relapse mortality (NRM), relapse incidence, progression-free survival (PFS), and overall survival (OS). Seventy-nine patients were ≥65 years old. Median time from diagnosis to ASCT was longer in the elderly patients (11 versus 9 months, P=0.005); they had more commonly received at least two treatment lines (62.0% versus 47.9%, P=0.02) and were less commonly in first complete remission at ASCT (35.4% versus 51.2%, P=0.002). Median follow-up after ASCT was 19 and 25 months, respectively. NRM was comparable at 3 months (3.8% versus 2.5%) and at 5 years (5.6% versus 5.0%). There were no differences in relapse rate (66% versus 55% at 5 years), PFS (29% versus 40%) and OS (61% versus 67%) between both populations of patients. ASCT beyond 65 years of age is feasible in selected patients with MCL and results in similar disease control and survival as in younger patients.
    Full-text Article · Apr 2011 · Annals of Oncology
  • Conference Paper · Apr 2011

Publication Stats

5k Citations


  • 2005-2015
    • Université René Descartes - Paris 5
      • • Faculté de Médecine
      • • Faculté de Médecine
      Lutetia Parisorum, Île-de-France, France
  • 2009
    • Hôpital Universitaire Necker
      Lutetia Parisorum, Île-de-France, France
    • Hospices Civils de Lyon
      Lyons, Rhône-Alpes, France
  • 2007
    • Unité Inserm U1077
      Caen, Lower Normandy, France
  • 2006
    • Hôpital Universitaire Robert Debré
      Lutetia Parisorum, Île-de-France, France