115 results on '"Blaise, Didier"'
Search Results
2. Posttransplant cyclophosphamide versus anti‐thymocyte globulin versus combination for graft‐versus‐host disease prevention in haploidentical transplantation for adult acute myeloid leukemia: A report from the European Society for Blood and Marrow Transplantation Acute Leukemia Working Party
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Bazarbachi, Abdul‐Hamid, Labopin, Myriam, Raiola, Anna Maria, Blaise, Didier, Arcese, William, Santarone, Stella, Koc, Yener, Bramanti, Stefania, Kulagin, Alexander, Kwon, Mi, Sica, Simona, Sanz, Jaime, Brissot, Eolia, Nagler, Arnon, Ciceri, Fabio, and Mohty, Mohamad
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ACUTE myeloid leukemia ,STEM cell transplantation ,CORD blood ,TREATMENT effectiveness ,BONE marrow - Abstract
Background: The optimal choice for graft‐versus‐host disease (GVHD) prophylaxis in haploidentical stem cell transplantation (haplo‐SCT) remains debatable. Posttransplant cyclophosphamide (PTCy) and anti‐thymocyte globulin (ATG) are two common strategies, but little is known about their combination. Methods: Using the European Society for Blood and Marrow Transplantation (EBMT) registry, the authors identified 3649 adult patients with acute myeloid leukemia (AML) who underwent haplo‐SCT in complete remission between 2007 and 2021 at 260 EBMT‐participating centers who received either PTCy (n = 2999), ATG (n = 358), or combination prophylaxis (n = 292). Cord blood transplants, combined bone marrow and peripheral grafts, and transplants with ex vivo graft manipulation were excluded. Median follow‐up was 31.8 months. Results: On multivariate analysis, adjusting for patient age and performance status, disease status at transplant, cytogenetic risk, conditioning intensity, stem cell source, female‐to‐male graft, and donor and patient CMV status, we present the following. Compared to PTCy, ATG had a higher risk of nonrelapse mortality (hazard ratio [HR], 1.6; p =.003), worse leukemia‐free survival (HR, 1.4; p =.002), overall survival (HR, 1.49; p =.0009), and GVHD‐free and relapse‐free survival (HR, 1.29; p =.012). The combination of PTCy and ATG, however, led to significantly reduced rates of grade 2–4 (HR, 0.51; p =.0003) and grade 3–4 (HR, 0.5; p =.018) acute GVHD and did not affect any transplant outcomes compared to PTCy without ATG. Conclusion: The authors conclude that ATG alone is a less effective prophylaxis strategy compared to PTCy, however, the combination of PTCy and ATG is superior to either monotherapy. They propose that this combination could be considered a potential new standard of care for GVHD prophylaxis in haplo‐SCT for AML. This study analyzed 3649 adult acute myeloid leukemia (AML) patients undergoing haploidentical stem cell transplantation (haplo‐SCT) with either posttransplant cyclophosphamide (PTCy), anti‐thymocyte globulin (ATG), or their combination, and showed that ATG alone had worse outcomes compared to PTCy, but combining PTCy and ATG significantly reduced acute graft‐vs‐host disease (GVHD) rates without affecting transplant outcomes. This suggests the PTCy and ATG combination could be a superior GVHD prophylaxis strategy in haplo‐SCT for AML. [ABSTRACT FROM AUTHOR]
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- 2024
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3. Prognostic impact of number of induction courses to attain complete remission in patients with acute myeloid leukemia transplanted with either a matched sibling or human leucocyte antigen 10/10 or 9/10 unrelated donor: An Acute Leukemia Working Party European Society for Blood and Marrow Transplantation study
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Loke, Justin, Labopin, Myriam, Craddock, Charles, Socié, Gérard, Gedde‐Dahl, Tobias, Blaise, Didier, Forcade, Edouard, Salmenniemi, Urpu, Huynh, Anne, Versluis, Jurjen, Yakoub‐Agha, Ibrahim, Labussière‐Wallet, Hélène, Maertens, Johan, Passweg, Jakob, Bulabois, Claude Eric, Gabellier, Ludovic, Mielke, Stephan, Castilla‐Llorente, Cristina, Deconinck, Eric, and Brissot, Eolia
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ACUTE myeloid leukemia ,ACUTE leukemia ,STEM cell transplantation ,LEUCOCYTES ,BONE marrow - Abstract
Introduction: For the majority of patients with acute myeloid leukemia (AML) an allogeneic stem cell transplant (SCT) in first complete remission (CR) is preferred. However, whether the number of courses required to achieve CR has a prognostic impact is unclear. It is unknown which factors remain important in patients requiring more than one course of induction to attain remission. Methods: This Acute Leukaemia Working Party study from the European Society for Blood and Marrow Transplantation identified adults who received an allograft in first CR from either a fully matched sibling or 10/10 or 9/10 human leucocyte antigen (HLA)‐matched unrelated donor (HLA‐A, HLA‐B, HLA‐C, HLA‐DR, or HLA‐DQ). Univariate and multivariate analyses were undertaken to identify the prognostic impact of one or two courses of induction to attain CR. Results: A total of 4995 patients were included with 3839 (77%) patients attaining a CR following one course of induction chemotherapy (IND1), and 1116 patients requiring two courses (IND2) to attain CR. IND2 as compared to IND1 was a poor prognostic factor in a univariate analysis and remained so in a multivariate Cox model, resulting in an increased hazard ratio of relapse (1.38; 95% confidence interval [CI], 1.16–1.64; p =.0003) and of death (1.27; 95% CI, 1.09–1.47; p =.002). Adverse prognostic factors in a multivariate analysis of the outcomes of patients requiring IND2 included age, FLT3‐ITD, adverse cytogenetics, and performance status. Pretransplant measurable residual disease retained a prognostic impact regardless of IND1 or IND2. Conclusion: Initial response to chemotherapy as determined by number of courses to attain CR, retained prognostic relevance even following SCT in CR. Patients requiring two courses of induction to attain complete remission (CR) have a higher incidence of relapse and inferior survival as compared to those who require one course. Pretransplant measurable residual disease remains important in predicting outcomes following an allogeneic stem cell transplant in those requiring two courses of induction to achieve CR. [ABSTRACT FROM AUTHOR]
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- 2024
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4. Lower relapse incidence with HAPLO versus MSD or MUD HCTs for AML patients with KMT2A rearrangement: a study from the Global Committee and the ALWP of the EBMT.
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Ye, Yishan, Labopin, Myriam, Chen, Jia, Wu, Depei, Gedde-Dahl Sr., Tobias, Blaise, Didier, Socie, Gérard, Forcade, Edouard, Salmenniemi, Urpu, Maury, Sébastien, Versluis, Jurjen, Bazarbachi, Ali, Nagler, Arnon, Brissot, Eolia, Li, Lin, Luo, Yi, Shi, Jimin, Ciceri, Fabio, Huang, He, and Mohty, Mohamad
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ACUTE myeloid leukemia ,MUD ,CORD blood ,HEMATOPOIETIC stem cell transplantation - Abstract
A study published in the Blood Cancer Journal examined the outcomes of allogeneic hematopoietic stem cell transplantation (HCT) in adult patients with adverse-risk acute myeloid leukemia (AML) and KMT2A rearrangement. The study found that haploidentical donor HCT (Haplo-HCT) had a lower relapse incidence compared to matched sibling donor (MSD) or matched unrelated donor (MUD) transplants. The study also investigated the prognostic value of different KMT2A fusion partners. The findings suggest that Haplo-HCT may be beneficial for AML patients with adverse-risk KMT2A rearrangement, excluding t(9;11), in terms of relapse prevention. [Extracted from the article]
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- 2024
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5. Allogeneic hematopoietic cell transplantation with cord blood versus mismatched unrelated donor with post-transplant cyclophosphamide in acute myeloid leukemia
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Dholaria, Bhagirathbhai, Labopin, Myriam, Sanz, Jaime, Ruggeri, Annalisa, Cornelissen, Jan, Labussière-Wallet, Hélène, Blaise, Didier, Forcade, Edouard, Chevallier, Patrice, Grassi, Anna, Zubarovskaya, Ludmila, Kuball, Jürgen, Ceballos, Patrice, Ciceri, Fabio, Baron, Frederic, Savani, Bipin N., Nagler, Arnon, and Mohty, Mohamad
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- 2021
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6. Allogeneic Stem Cell Transplantation for FLT3-Mutated Acute Myeloid Leukemia: In vivo T-Cell Depletion and Posttransplant Sorafenib Maintenance Improve Survival. A Retrospective Acute Leukemia Working Party-European Society for Blood and Marrow Transplant Study
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Bazarbachi, Ali, Labopin, Myriam, Battipaglia, Giorgia, Djabali, Azedine, Forcade, Edouard, Arcese, William, Socié, Gerard, Blaise, Didier, Halter, Joerg, Gerull, Sabine, Cornelissen, Jan J., Chevallier, Patrice, Maertens, Johan, Schaap, Nicolaas, El-Cheikh, Jean, Esteve, Jordi, Nagler, Arnon, and Mohty, Mohamad
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- 2019
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7. Post-transplant cyclophosphamide versus antithymocyte globulin in patients with acute myeloid leukemia in first complete remission undergoing allogeneic stem cell transplantation from 10/10 HLA-matched unrelated donors
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Brissot, Eolia, Labopin, Myriam, Moiseev, Ian, Cornelissen, J. J., Meijer, Ellen, Van Gorkom, Gwendolyn, Rovira, Montserrat, Ciceri, Fabio, Griskevicius, Laimonas, Blaise, Didier, Forcade, Edouard, Mistrik, Martin, Mielke, Stephan, Bulabois, Claude Eric, Niittyvuopio, Riitta, Deconinck, Eric, Ruggeri, Annalisa, Sanz, Jaime, Spyridonidis, Alexandros, Savani, Bipin, Giebel, Sebastian, Nagler, Arnon, and Mohty, Mohamad
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- 2020
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8. Unrelated or haploidentical allogeneic hematopoietic cell transplantation in second complete remission for acute myeloid leukemia—Improved outcomes over time: A European Society for Blood and Marrow Transplantation Acute Leukemia Working Party study
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Al Hamed, Rama, Ngoya, Maud, Galimard, Jacques‐Emmanuel, Sengeloev, Henrik, Gedde‐Dahl, Tobias, Kulagin, Aleksandr, Platzbecker, Uwe, Yakoub‐Agha, Ibrahim, Byrne, Jenny L., Valerius, Thomas, Socie, Gerard, Kröger, Nicolaus, Blaise, Didier, Bazarbachi, Ali, Sanz, Jaime, Ciceri, Fabio, Nagler, Arnon, and Mohty, Mohamad
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HEMATOPOIETIC stem cell transplantation ,ACUTE myeloid leukemia ,ACUTE leukemia ,TOTAL body irradiation ,BONE marrow - Abstract
Background: Allogeneic hematopoietic cell transplantation (allo‐HCT) is the only cure for acute myeloid leukemia (AML) in second complete remission (CR2). Patients lacking a matched sibling donor (MSD) receive transplants from matched unrelated donors (MUDs), mismatched unrelated donors (MMUDs), haploidentical (haplo) donors, or cord blood. Methods: This is a retrospective, registry‐based European Society for Blood and Marrow Transplantation study that investigates changes in patient‐ and transplant‐related characteristics and posttransplant outcomes over time. Results: We identified 3955 adult patients (46.7% female; median age, 52 years [range, 18–78 years]) with AML in CR2 first transplanted between 2005 and 2019 from a MUD 10/10 (61.4%), MMUD 9/10 (21.9%), or haplo donor (16.7%) and followed for 3.7 years. A total of 725 patients were transplanted between 2005 and 2009, 1600 between 2010 and 2014, and 1630 between 2015 and 2019. Over the three time periods, there was a significant increase in patient age (from 48.7 to 53.5 years; p <.001), use of a haplo donor (from 4.6% to 26.4%; p <.001), and use of posttransplant cyclophosphamide (from 0.4% to 29%; p <.001). There was a significant decrease in total body irradiation and in vivo T‐cell depletion. In multivariate analysis, transplants performed more recently had better outcomes. Leukemia‐free survival (hazard ratio [HR], 0.79; p =.002) and overall survival (HR, 0.73; p <.001) increased over time. Similarly, nonrelapse mortality (HR, 0.64; p <.001) decreased over time. We also observed better graft‐vs‐host disease (GVHD) rates (acute GVHD II–IV: HR, 0.78; p =.03; GVHD‐free, relapse‐free survival: HR, 0.69; p <.001). Conclusions: Even in the absence of an MSD, outcomes of allo‐HCT in CR2 for AML have significantly improved over time, with most favorable outcomes achieved with a MUD. Allogeneic transplantation remains the only curative option for patients with acute myeloid leukemia in second complete remission, with significant changes in patient and transplant characteristics and posttransplant outcomes over time. Even in the absence of matched sibling donors, outcomes have improved over time, with the best outcomes achieved with matched unrelated donors. [ABSTRACT FROM AUTHOR]
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- 2023
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9. Ex vivo and in vivo T cell-depleted allogeneic stem cell transplantation in patients with acute myeloid leukemia in first complete remission resulted in similar overall survival: on behalf of the ALWP of the EBMT and the MSKCC
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Malard, Florent, Labopin, Myriam, Cho, Christina, Blaise, Didier, Papadopoulos, Esperanza B., Passweg, Jakob, O’Reilly, Richard, Forcade, Edouard, Maloy, Molly, Volin, Liisa, Castro-Malaspina, Hugo, Hicheri, Yosr, Jakubowski, Ann A., Orvain, Corentin, Giralt, Sergio, Mohty, Mohamad, Nagler, Arnon, and Perales, Miguel-Angel
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- 2018
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10. Impact of measurable residual disease on outcomes of unrelated donor haematopoietic cell transplantation with post‐transplant cyclophosphamide in AML in first complete remission.
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Nagler, Arnon, Labopin, Myriam, Dholaria, Bhagirathbhai, Blaise, Didier, Bondarenko, Sergey, Vydra, Jan, Choi, Goda, Rovira, Montserrat, Reményi, Péter, Meijer, Ellen, Bulabois, Claude Eric, Diez‐Martin, J. L., Yakoub‐Agha, Ibrahim, Brissot, Eolia, Spyridonidis, Alexandros, Sanz, Jaime, Patel, Amit, Arat, Mutlu, Bazarbachi, Ali, and Bug, Gesine
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CELL transplantation ,ACUTE myeloid leukemia ,CYCLOPHOSPHAMIDE ,MULTIVARIATE analysis ,OVERALL survival - Abstract
Summary: Pre‐transplant measurable residual disease (MRD) predicts relapse and outcome of allogeneic haematopoietic cell transplantation (allo‐HCT). The impact of MRD on the outcomes of post‐transplant cyclophosphamide (PTCy)‐based allo‐HCT from a matched unrelated donor (UD) is unknown. This study assessed the impact of MRD in acute myeloid leukaemia (AML) in the first complete remission (CR1). A total of 272 patients (MRD negative [MRD−], n = 165; MRD positive [MRD+], n = 107) with a median follow‐up of 19 (range: 16–24) months were studied. The incidence of grades II–IV and grades III–IV acute GVHD at day 180 was 25.2% and 25% (p = 0.99), and 10.6% and 6.8% (p = 0.29), respectively, and 2‐year chronic GVHD was 35% and 30.4% (p = 0.96) in MRD+ and MRD− cohorts, respectively. In multivariate analysis, MRD+ status was associated with a higher incidence of relapse (RI) (hazard ratio [HR] = 2.56, 95% CI: 1.39–4.72), lower leukaemia‐free survival (LFS) (HR = 2.04, 95% CI: 1.23–3.39), overall survival (OS) (HR = 1.83, 95% CI: 1.04–3.25) and GVHD‐free, relapse‐free survival (GRFS) (HR = 1.69, 95% CI: 1.10–2.58). MRD status did not have a significant impact on non‐relapse mortality (NRM), or acute or chronic GVHD risk. Among patients with AML undergoing UD allo‐HCT with PTCy, pre‐transplant MRD+ status predicted a higher relapse rate, lower LFS, OS and GRFS. [ABSTRACT FROM AUTHOR]
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- 2023
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11. Non-T-depleted haploidentical transplantation with post-transplant cyclophosphamide in patients with secondary versus de novo AML in first complete remission: a study from the ALWP/EBMT.
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Nagler, Arnon, Labopin, Myriam, Blaise, Didier, Raiola, Anna Maria, Corral, Lucia Lopez, Bramanti, Stefania, Sica, Simona, Kwon, Mi, Koc, Yener, Pavlu, Jiri, Kulagin, Alexander, Busca, Alessandro, Rodríguez, Arancha Bermúdez, Reményi, Péter, Schmid, Christoph, Brissot, Eolia, Sanz, Jaime, Bazarbachi, Ali, Giebel, Sebastian, and Ciceri, Fabio
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ACUTE myeloid leukemia ,KARNOFSKY Performance Status ,STEM cell transplantation ,CYCLOPHOSPHAMIDE ,GRAFT versus host disease - Abstract
We compared outcomes of adult patients with secondary acute myeloid leukemia (sAML) versus de novo AML after non-T-depleted haploidentical stem cell transplant (HaploSCT) with post-transplant cyclophosphamide (PTCy). Seventeen hundred and eleven AML patients (sAML-231, de novo-1480) in first complete remission transplanted from 2010 to 2021, were included. Patients with de novo AML were younger, median age 55.8 versus 60.8 years, p < 0.0001, had better transplantation comorbidity index (HCT-CI) ≥ 3 21.3% versus 40.8%, p < 0.0001 and Karnofsky performance status (KPS) with KPS ≥ 90 in 78% versus 68.5%, respectively, p = 0.002. The two patient groups did not differ with respect to gender, cytomegalovirus serostatus, and cell source. Median time from diagnosis to HaploSCT was 5.2 versus 4.9 months, respectively, p = 0.005. Fewer sAML patients received myeloablative conditioning 35.1% versus 50.1%, p < 0.0001. Two hundred and eleven sAML and 410 de novo AML patients were included in the matched-pair analysis matching two de novo AML with each sAML. No significant difference was observed in any transplantation outcome parameter between the sAML versus de novo AML groups. Two-year non-relapse mortality and relapse incidence did not differ with HaploSCT for de novo versus sAML; 21.4% versus 21%, hazard ratio (HR) = 0.98, p = 0.9 and 23.4% versus 20.6%, HR = 0.92, p = 0.67, respectively. Two-year leukemia-free survival, overall survival, and graft-versus-host disease (GVHD)-free, relapse-free survival were also not different between the de novo AML and sAML groups 55.2% versus 58.4%, HR = 0.95, p = 0.67; 61.4% versus 66.4%, HR = 0.91, p = 0.51 and 46.3% versus 48.2%, HR = 0.92, p = 0.48, respectively. Similarly, the incidence of engraftment as well as acute and chronic GVHD was similar between the 2 cohorts. In conclusion, HaploSCT with PTCy may be able to overcome the bad prognosis of sAML as results are not significantly different to those of HaploSCT in de novo AML. [ABSTRACT FROM AUTHOR]
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- 2023
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12. Haploidentical transplantation is associated with better overall survival when compared to single cord blood transplantation: an EBMT-Eurocord study of acute leukemia patients conditioned with thiotepa, busulfan, and fludarabine
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Giannotti, Federica, Labopin, Myriam, Shouval, Roni, Sanz, Jaime, Arcese, William, Angelucci, Emanuele, Sierra, Jorge, Santasusana, Josep-Maria Ribera, Santarone, Stella, Benedetto, Bruno, Rambaldi, Alessandro, Saccardi, Riccardo, Blaise, Didier, Carella, Michele Angelo, Rocha, Vanderson, Baron, Frederic, Mohty, Mohamad, Ruggeri, Annalisa, and Nagler, Arnon
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- 2018
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13. Similar outcomes following non-first-degree and first-degree related donor haploidentical hematopoietic cell transplantation for acute leukemia patients in complete remission: a study from the Global Committee and the Acute Leukemia Working Party of the European Society for Blood and Marrow Transplantation
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Ye, Yishan, Labopin, Myriam, Chen, Jia, Gulbas, Zafer, Zhang, Xi, Koc, Yener, Blaise, Didier, Ciceri, Fabio, Polge, Emmanuelle, Houhou, Mohamed, Li, Lin, Luo, Yi, Wu, Depei, Huang, He, Mohty, Mohamad, and Gorin, Norbert-Claude
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HEMATOPOIETIC stem cell transplantation ,ACUTE leukemia ,LYMPHOBLASTIC leukemia ,ACUTE myeloid leukemia ,BONE marrow - Abstract
There are situations where non-first-degree (NFD) related donors have to be considered as alternatives to first-degree (FD) related donors for haploidentical hematopoietic cell transplantation (HAPLO). However, the efficacy of these NFD related transplants remains uncertain. All consecutive adult patients (≥ 18 years) with acute myelogenous leukemia (AML) or acute lymphocytic leukemia (ALL) in CR who underwent a first HAPLO between 2010 and 2021 in the European Society for Blood and Marrow Transplantation (EBMT) registry were analyzed. Exact matching and propensity score matching was used. The NFD-to-FD ratio was 1:3. 2703 patients (AML: n = 2047; ALL: n = 656) in CR received a first HAPLO from either NFD (n = 154) or FD (n = 2549) related donors in 177 EBMT centers. 123 NFD and 324 FD HAPLO were included for analysis after matching. Median patient age was 35.6 and 37.2 for the NFD and FD cohorts, respectively. Both cohorts reached good engraftment rates (NFD: 95.7% vs. FD, 95.6%; p = 0.78). The 2-year relapse incidence (NFD, 21.1% vs. FD, 22.6%; p = 0.84) and non-relapse mortality (NRM) (NFD, 13.2% vs. FD, 17.7%; p = 0.33) were not significantly different. The 2-year overall survival (OS) (NFD, 71.8% vs. FD, 68.3%; p = 0.56), leukemia-free survival (LFS) (NFD, 65.7% vs. FD, 59.7%; p = 0.6) and graft-versus-host disease (GVHD)-free, relapse-free survival (GRFS) (NFD, 50.9% vs. FD, 47.8%; p = 0.69) also showed no significant differences. The two cohorts showed no difference in terms of cumulative day 180 grade II-IV, grade III-IV acute GVHD, 2-year cumulative incidences of chronic and extensive chronic GVHD. For HAPLO in patients with acute leukemia, NFD related donors could be equivalent substitutions when FD related donors are not available. [ABSTRACT FROM AUTHOR]
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- 2023
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14. Autologous stem cell transplantation (ASCT) for acute myeloid leukemia in patients in first complete remission after one versus two induction courses: A study from the ALWP of the EBMT.
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Nagler, Arnon, Galimard, Jacques‐Emmanuel, Labopin, Myriam, Blaise, Didier, Arcese, William, Trisolini, Silvia Maria, Wu, Depei, Pigneux, Arnaud, Van Gorkom, Gwendolyn, Rubio, Marie‐Thérèse, Gedde‐Dahl, Tobias, Huynh, Anne, Lanza, Francesco, Gorin, Norbert‐Claude, and Mohty, Mohamad
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STEM cell transplantation ,ACUTE myeloid leukemia ,CURRICULUM ,INDUCTION chemotherapy - Abstract
Background: Achieving complete remission (CR) is the main goal in AML treatment and a prerequisite for successful autologous stem cell transplantation (ACT). Methods: Comparing results of peripheral blood ACT in patients with AML in CR1 attained following 1 versus 2 chemotherapy courses transplanted in 2000–2019. Results: Patients 1532 (84%) with one and 293 (16%) patients with two induction chemotherapies courses (a total of 1825 patients) were included in the study. Follow‐up was 7.9 (95% CI: 7.4–8.4) and 7.7 (95% CI: 7.0–8.6) years (p = 0.8). Time from diagnosis to ACT was 4.7 (range, 3.9–5.8) versus 5.7 (range, 4.7–7.1) months (p < 0.001), respectively. Leukemia free survival (LFS) and overall survival (OS) at 5 years were inferior for patients achieving CR1 with 2 versus 1 course of chemotherapy: 26.6% versus 41.7% (HR = 1.42 [95% CI: 1.22–1.66], p < 0.001) and 36.2% versus 53.3%, (HR = 1.48 [95% CI: 1.25–1.75], p < 0.001), and 5‐year relapse incidence (RI) was higher: 67.2% versus 52.3%, (HR = 1.46 [95% CI: 1.25–1.72], p < 0.001). Five‐year non‐relapse mortality (NRM) was 6.2% versus 6.0% for patients with 2 versus 1 chemotherapy courses, and did not differ significantly (HR = 1.31 [95% CI: 0.81–2.10], p = 0.27). Conclusions: LFS and OS were inferior and relapse rate was higher in AML patients who received two inductions chemotherapy courses to reach CR1 before being autografted. AML patients who required 2 induction courses to achieve remission, may be offered allogeneic transplantation rather than an autologous one in an attempt to reduce their high RI and improve outcomes. [ABSTRACT FROM AUTHOR]
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- 2023
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15. Chemotherapy or Allogeneic Stem Cell Transplantation as Salvage Therapy for Patients with Refractory Acute Myeloid Leukemia: A Multicenter Analysis.
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Wang, Zhong-yu, Gao, Wen-hui, Zhao, Hui-jin, Yin, Chun-rong, Wang, Zi-wei, Tian, Liang, Wang, Ling, Wang, Li-ning, Jiang, Jie-ling, Devillier, Raynier, Wan, Ming, Wang, Jian-Ming, Huang, Ping-ping, Blaise, Didier, and Hu, Jiong
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STEM cell transplantation ,ACUTE myeloid leukemia ,SALVAGE therapy ,HEMATOPOIETIC stem cell transplantation ,CANCER chemotherapy ,MUCOSITIS - Abstract
Introduction: The overall outcome of patients with refractory AML (rAML) remains poor. Though allogeneic hematopoietic stem cell transplantation (allo-HSCT) is considered as the only curative therapy, it is routinely recommended only for patients after remission with salvage chemotherapy. Objective: In this study, we evaluated the impact of salvage chemotherapy or allo-HSCT on the overall outcome in rAML. Methods: We collected the clinical data of 220 patients from 4 medical centers and performed retrospective analysis of prognosis factors, including salvage chemotherapy, intensity of chemotherapy, and allo-HSCT. Results: A total of 29 patients received allo-HSCT directly without salvage chemotherapy, 26 patients achieved complete remission (CR) or complete remission with incomplete hematological recovery (CRi) after transplantation and 4-year leukemia-free survival (LFS) and overall survival (OS) were 45.0 ± 10.7 and 51.0 ± 10.6%, respectively. Another 191 patients received salvage chemotherapy and 81 (42.2%) achieved CR or CRi. Thirty-four patients among them underwent subsequent allo-HSCT with 4-year LFS and OS of 46.0 ± 8.8 and 46.2 ± 9.0%. The 4-year LFS and OS in 26 patients who failed to obtain CR or CRi but received allo-HSCT with active disease were 32.9 ± 10.0 and 36.9 ± 10.8%, respectively. For patients who received salvage chemotherapy but not allo-HSCT, few of them became long-term survivors. In multivariate analysis, salvage chemotherapy and the intensity of chemotherapy failed to have significant impact on both OS and LFS. Allo-HSCT was the only prognostic factor for improved OS and LFS in multivariate analysis. Conclusions: These results indicate the benefit of allo-HSCT in patients with rAML and direct allo-HSCT without salvage chemotherapy could be treatment option. [ABSTRACT FROM AUTHOR]
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- 2022
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16. Measurable residual disease, FLT3-ITD mutation, and disease status have independent prognostic influence on outcome of allogeneic stem cell transplantation in NPM1-mutated acute myeloid leukemia.
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Al Hamed, Rama, Labopin, Myriam, Daguindau, Etienne, Niittyvuopio, Riitta, Huynh, Anne, Socié, Gerard, Srour, Micha, Bourhis, Jean Henri, Kröger, Nicolaus, Tholouli, Eleni, Choi, Goda, Poiré, Xavier, Martin, Hans, Rubio, Marie-Thérèse, Jindra, Pavel, Blaise, Didier, Beelen, Dietrich, Labussière-Wallet, Hélène, Nagler, Arnon, and Bazarbachi, Ali
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ACUTE myeloid leukemia ,STEM cell transplantation ,HEMATOPOIETIC stem cell transplantation ,KARNOFSKY Performance Status - Abstract
Nucleophosmin-1 (NPM1) mutations in acute myeloid leukemia (AML) confer a survival advantage in the absence of FLT3-internal tandem duplication (FLT3-ITD). Here, we investigated the main predictors of outcome after allogeneic hematopoietic stem cell transplantation (allo-HCT). We identified 1572 adult (age ≥ 18 year) patients with NPM1-mutated AML in first complete remission (CR1:78%) or second complete remission (CR2:22%) who were transplanted from matched sibling donors (30.8%) or unrelated donors (57.4%) between 2007 and 2019 at EBMT participating centers. Median follow-up for survivors was 23.7 months. FLT3-ITD was present in 69.3% of patients and 39.2% had detectable minimal/measurable residual disease (MRD) at transplant. In multivariate analysis, relapse incidence (RI) and leukemia-free survival (LFS) were negatively affected by concomitant FLT3-ITD mutation (HR 1.66 p = 0.0001, and HR 1.53, p < 0.0001, respectively), MRD positivity at transplant (HR 2.18, p < 10-5 and HR 1.71, p < 10-5, respectively), and transplant in CR2 (HR 1.36, p = 0.026, and HR 1.26, p = 0.033, respectively), but positively affected by Karnofsky score ≥90 (HR 0.74, p = 0.012, and HR 0.7, p = 0.0002, respectively). Overall survival (OS) was also negatively influenced by concomitant FLT3-ITD (HR 1.6, p = 0.0001), MRD positivity at transplant (HR 1.61, p < 10-5), and older age (HR 1.22 per 10 years, p < 0.0001), but positively affected by matched sibling donor (unrelated donor: HR 1.35, p = 0.012; haploidentical donor: HR 1.45, p = 0.037) and Karnofsky score ≥90 (HR 0.73, p = 0.004). These results highlight the independent and significant role of FLT3-ITD, MRD status, and disease status on posttransplant outcomes in patients with NPM1-mutated AML allowing physicians to identify patients at risk of relapse who may benefit from posttransplant prophylactic interventions. [ABSTRACT FROM AUTHOR]
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- 2022
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17. Second allogeneic haematopoietic cell transplantation using HLA‐matched unrelated versus T‐cell replete haploidentical donor and survival in relapsed acute myeloid leukaemia.
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Kharfan‐Dabaja, Mohamed A., Labopin, Myriam, Brissot, Eolia, Kroger, Nicolaus, Finke, Jürgen, Ciceri, Fabio, Deconinck, Eric, Blaise, Didier, Chevallier, Patrice, Gramatzki, Martin, Ganser, Arnold, Stelljes, Matthias, Edinger, Matthias, Savani, Bipin, Ruggeri, Annalisa, Sanz, Jaime, Nagler, Arnon, and Mohty, Mohamad
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ACUTE myeloid leukemia ,CELL transplantation ,ACUTE leukemia ,AGE groups - Abstract
Summary: Optimal donor choice for a second allogeneic haematopoietic cell transplant (allo‐HCT) in relapsed acute myeloid leukaemia (AML) remains unknown. We compared overall survival (OS) using registry data from the Acute Leukemia Working Party (ALWP) of the European Society for Blood and Marrow Transplantation (EBMT) involving 455 adults who received a second allo‐HCT from a human leucocyte antigen (HLA)‐matched unrelated (MUD) (n = 320) or a haploidentical (n = 135) donor. Eligibility criteria required adults aged ≥18 years who received a second allo‐HCT for treating AML relapse between 2005 and 2019. The primary end‐point was OS. There was no statistically significant difference in the median (interquartile range) age between the groups, MUD 46 (35–58) versus haploidentical 44 (33–53) years (P = 0·07). The median OS was not different between the MUD and the haploidentical groups (10 vs. 11 months, P = 0·57). Similarly, the 2‐year OS was 31% for the MUD and 29% for the haploidentical donor groups. The OS was worse if the procedure was performed with active AML [hazard ratio (HR) 1·42, 95% confidence interval (CI) 1·07–1·89; P = 0·02]. Conversely, a longer time from first allo‐HCT to relapse (>13·2 months) was associated with better OS (HR 0·50, 95% CI 0·37–0·69; P < 0·0001). The results of the present analysis limit the ability to recommend one donor type over another when considering a second allo‐HCT for relapsed AML. Our findings highlight that best OS is achieved when receiving the second allo‐HCT in complete remission. [ABSTRACT FROM AUTHOR]
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- 2021
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18. T-cell replete haploidentical stem cell transplantation attenuates the prognostic impact of FLT3-ITD in acute myeloid leukemia. A report from the Acute Leukemia Working Party of the EBMT
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Canaani, Jonathan, Labopin, Myriam, Huang, Xiao-Jun, Arcese, William, Ciceri, Fabio, Blaise, Didier, Irrera, Giuseppe, Lopez Corral, Lucia, Bruno, Benedetto, Santarone, Stella, Van Lint, Maria Teresa, Vitek, Antonin, Esteve, Jordi, Mohty, Mohamad, and Nagler, Arnon
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Acute myeloid leukemia ,FLT3-ITD ,haploidentical hematopoietic stem cell transplantation - Published
- 2018
19. Post‐transplantation cyclophosphamide versus antithymocyte globulin in patients with acute myeloid leukemia undergoing allogeneic stem cell transplantation from HLA‐identical sibling donors: A retrospective analysis from the Acute Leukemia Working Party of the European Society for Blood and Marrow Transplantation
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Battipaglia, Giorgia, Labopin, Myriam, Hamladji, Rose‐Marie, Blaise, Didier, Chevallier, Patrice, Brissot, Eolia, Gerbitz, Armin, Socié, Gerard, Afanasyev, Boris, Ciceri, Fabio, Meijer, Ellen, Koc, Yener, Cornelissen, Jan J., Huynh, Anne, Ozdogu, Hakan, Maertens, Johan, Paul, Franciane, Labussière‐Wallet, Hélène, Ruggeri, Annalisa, and Aljurf, Mahmoud
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ACUTE myeloid leukemia ,STEM cell transplantation ,TOTAL body irradiation ,ACUTE leukemia ,CYCLOPHOSPHAMIDE ,HEMATOPOIETIC stem cell transplantation - Abstract
BACKGROUND: Graft‐versus‐host disease (GVHD) is a major complication after allogeneic hematopoietic stem cell transplantation (allo‐HSCT). Addition of antithymocyte globulin (ATG) or post‐transplantation cyclophosphamide (PTCY) to standard immunosuppressive agents reduces GVHD in different donor settings. METHODS: We compared the outcomes of adults with acute myeloid leukemia undergoing allo‐HSCT from HLA‐identical sibling donors after the use of PTCY (n = 197) or ATG (n = 1913). RESULTS: Patients in the PTCY group were younger than those in the ATG group (median age, 47 vs 54 years; P <.01). Peripheral blood was the most frequently used stem cell source, being significantly more frequent in the ATG group than in the PTCY group (95% vs 70% P <.01). The conditioning regimen was more frequently myeloablative in the PTCY group than in the ATG group (59% vs 48%; P <.01). Time to neutrophil engraftment was shorter in the ATG group than in the PTCY group (17 vs 20 days; P <.01). No differences were observed according to the other transplantation outcomes, except for chronic GVHD of all grades and extensive chronic GVHD at 2 years, which were significantly lower in the ATG group compared with the PTCY group (P <.02). CONCLUSION: PTCY is feasible in an HLA‐identical sibling setting, and despite similar outcomes, ATG may be associated with lower incidence of chronic GVHD. Addition of antithymocyte globulin (ATG) or post‐transplantation cyclophosphamide (PTCY) to standard immunosuppressive agents in patients who received a transplant from an HLA‐identical sibling donor is feasible and allows low rates of graft‐versus‐host disease (GVHD).When compared with PTCY, the use of ATG is associated with lower cumulative incidence of chronic GVHD. [ABSTRACT FROM AUTHOR]
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- 2021
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20. Allogeneic stem cell transplant in patients with acute myeloid leukemia and karnofsky performance status score less than or equal to 80%: A study from the acute leukemia working party of the European Society for Blood and Marrow Transplantation (EBMT).
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Saraceni, Francesco, Labopin, Myriam, Forcade, Edouard, Kröger, Nicolaus, Socié, Gerard, Niittyvuopio, Riitta, Cornelissen, Jan J., Labussière‐Wallet, Hélène, Blaise, Didier, Choi, Goda, Byrne, Jenny L., Guillerm, Gaelle, Marchand, Tony, Esteve, Jordi, Bazarbachi, Ali, Savani, Bipin, Olivieri, Attilio, Nagler, Arnon, and Mohty, Mohamad
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KARNOFSKY Performance Status ,ACUTE myeloid leukemia ,STEM cell transplantation ,ACUTE leukemia ,BONE marrow - Abstract
Limited data are currently available on the outcome of patients with acute myeloid leukemia (AML) undergoing allogeneic stem cell transplantation (allo‐SCT) with a reduced performance status. We herein present the results of a registry study on 2,936 AML patients undergoing allo‐SCT in first remission (CR1) with a Karnofsky Performance Status (KPS) score less than or equal to 80%. Two‐year leukemia‐free survival (LFS), overall survival (OS) and graft‐versus‐host disease (GVHD)‐free, and relapse‐free survival (GRFS) rates were 54%, 59%, and 41%, respectively. In multivariable analysis, patients with a KPS score = 80% had lower non‐relapse mortality (NRM) and superior OS in comparison to patients with a KPS score <80% (p < 0.001). In the subgroup of patients with a KPS score =80%, a reduced‐intensity conditioning (RIC) regimen was associated with an increased risk of relapse (p = 0.002) and lower GRFS (p < 0.001) compared to myeloablative conditioning (MAC). Differently, in patients with a KPS score <80%, a RIC regimen resulted in lower NRM (p < 0.001), whereas relapse incidence did not differ, thus leading to an improved GRFS (p = 0.008) as compared to MAC. A transplant from a matched sibling donor (MSD) was associated with a reduced incidence of grade III‐IV acute GVHD (p < 0.01) and NRM (p < 0.01) in comparison to other donor types. In conclusion, allo‐SCT appears feasible in AML patients with a jeopardized KPS score. Survival is significantly affected by the conditioning intensity, which should be adjusted according to the severity of KPS impairment. [ABSTRACT FROM AUTHOR]
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- 2021
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21. Correction: Non-T-depleted haploidentical transplantation with post-transplant cyclophosphamide in patients with secondary versus de novo AML in first complete remission: a study from the ALWP/EBMT.
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Nagler, Arnon, Labopin, Myriam, Blaise, Didier, Raiola, Anna Maria, Corral, Lucia Lopez, Bramanti, Stefania, Sica, Simona, Kwon, Mi, Koc, Yener, Pavlu, Jiri, Kulagin, Alexander, Busca, Alessandro, Rodríguez, Arancha Bermúdez, Reményi, Péter, Schmid, Christoph, Brissot, Eolia, Sanz, Jaime, Bazarbachi, Ali, Giebel, Sebastian, and Ciceri, Fabio
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ACUTE myeloid leukemia ,CYCLOPHOSPHAMIDE ,HEMATOLOGY ,ONCOLOGY ,PATIENTS - Abstract
Reference 1 Nagler A. Non-T-depleted haploidentical transplantation with post-transplant cyclophosphamide in patients with secondary versus de novo AML in first complete remission: a study from the ALWP/EBMT. The correct affiliation can be viewed ahead in this Correction article: SP 7 sp Transplantation Unit Department of Oncology and Haematology, IRCCS Humanitas Research Hospital, Milan, Italy. [Extracted from the article]
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- 2023
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22. Clofarabine versus fludarabine-based reduced-intensity conditioning regimen prior to allogeneic transplantation in adults with AML/MDS
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Chevallier, Patrice, Labopin, Marie, de La Tour, Régis Peffault, Lioure, Bruno, Bulabois, Claude-Eric, Huynh, Anne, Blaise, Didier, Turlure, Pascal, Daguindau, Etienne, Maillard, Natacha, Yakoub-Agha, Ibrahim, Guillerm, Gaelle, Delage, Jeremy, Contentin, Nathalie, Bay, Jacques-Olivier, Beckerich, Florence, Bourhis, Jean-Henri, Detrait, Marie, Vigouroux, Stéphane, Francois, Sylvie, Legrand, Faézeh, Guillaume, Thierry, Mohty, Mohamad, Tc, Sfgm, Centre hospitalier universitaire de Nantes (CHU Nantes), Pathologies biliaires, fibrose et cancer du foie, Centre de Recherche Saint-Antoine (UMRS893), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Université Pierre et Marie Curie - Paris 6 - UFR de Médecine Pierre et Marie Curie (UPMC), Université Pierre et Marie Curie - Paris 6 (UPMC), Service d'Hémato-oncologie [CHU Saint-Louis], Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Département d'Oncologie et Hématologie [Strasbourg], Les Hôpitaux Universitaires de Strasbourg (HUS), Département de cancérologie et d'hématologie, CHU Grenoble-Hôpital Michallon, Institut Universitaire du Cancer de Toulouse - Oncopole (IUCT Oncopole - UMR 1037), Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université de Toulouse (UT)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC), Service d'Hématologie clinique et thérapie cellulaire [CHU Limoges], CHU Limoges, Service d'hématologie, Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon), Centre hospitalier universitaire de Poitiers (CHU Poitiers), Lille Inflammation Research International Center - U 995 (LIRIC), Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), CHRU Brest - Service d'Hématologie (CHU-Brest-Hemato), Centre Hospitalier Régional Universitaire de Brest (CHRU Brest), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Laboratoire d'hématologie [Rouen], CHU Rouen, Normandie Université (NU)-Normandie Université (NU)-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU), CHU Clermont-Ferrand, Service d'hématologie clinique, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Henri Mondor-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Département d'hématologie [Gustave Roussy], Institut Gustave Roussy (IGR), Hospices Civils de Lyon (HCL), CHU Bordeaux [Bordeaux], Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM), Centre Hospitalier Universitaire de Nice (CHU Nice), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-CHU Toulouse [Toulouse]-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Institut Pasteur de Lille, and Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)
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Male ,Oncology ,Cancer Research ,Transplantation Conditioning ,reduced-toxicity conditioning regimen ,0302 clinical medicine ,allogeneic stem cell transplantation ,hemic and lymphatic diseases ,Antineoplastic Combined Chemotherapy Protocols ,Clofarabine ,Original Research ,reduced‐toxicity conditioning regimen ,Adenine Nucleotides ,Incidence (epidemiology) ,Hematopoietic Stem Cell Transplantation ,Middle Aged ,lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,3. Good health ,Fludarabine ,Leukemia, Myeloid, Acute ,Treatment Outcome ,030220 oncology & carcinogenesis ,Female ,Vidarabine ,medicine.drug ,Adult ,medicine.medical_specialty ,Allogeneic transplantation ,[SDV.CAN]Life Sciences [q-bio]/Cancer ,Lower risk ,lcsh:RC254-282 ,Young Adult ,03 medical and health sciences ,Internal medicine ,medicine ,Humans ,Transplantation, Homologous ,Radiology, Nuclear Medicine and imaging ,Aged ,Retrospective Studies ,Acute myeloid leukemia ,business.industry ,fludarabine ,Clinical Cancer Research ,Surgery ,myelodysplastic syndrome ,Transplantation ,Regimen ,clofarabine ,Myelodysplastic Syndromes ,Arabinonucleosides ,business ,Busulfan ,[SDV.MHEP]Life Sciences [q-bio]/Human health and pathology ,Follow-Up Studies ,030215 immunology - Abstract
International audience; We have retrospectively compared survivals between acute myeloid leukemia (AML)/myelodysplastic syndrome (MDS) patients who received either a clofarabine/busulfan (CloB2A2) or a fludarabine/busulfan (FB2A2) RIC regimen for allogeneic stem cell transplantation. Between 2009 and 2014, 355 allotransplanted cases were identified from the SFGM-TC registry as having received either the FB2A2 (n = 316, 56% males, median age: 59.2 years, AML 78.5%, first complete remission [CR1] 72%, median follow-up: 20 months) or the CloB2A2 (n = 39, 62% males, median age: 60.8 years, AML 62%, CR1 69%, median follow-up: 22.4 months) RIC regimen. In multivariate analysis, FB2A2 was associated with significant lower overall survival (OS, HR: 2.14; 95%CI: 1.05-4.35, P = 0.04) and higher relapse incidence (RI, HR: 2.17; 95%CI: 1.02-4.61, P = 0.04) and a trend for lower leukemia-free survival (LFS, HR: 1.75; 95%CI: 0.94-3.26, P = 0.08). These results were confirmed using a propensity score-matching strategy. However, when considering AML and MDS patients separately, the benefit of the CLOB2A2 regimen was restricted to AML patients (2-year OS FB2A2: 38% [14.5-61.6] vs. CloB2A2: 79.2% [62.9-95.4], P = 0.01; 2-year LFS FB2A2: 38% [16-59.9] vs. CloB2A2: 70.8% [52.6-89], P = 0.03). The better survivals were due to the lower risk of relapse in this CloB2A2 AML subgroup (2-year RI FB2A2: 41.2% [19-62.4] vs. CloB2A2: 16.7% [5-34.2], P = 0.05). This retrospective comparison suggests that the CloB2A2 RIC regimen can likely provide longer survival than that awarded by a FB2A2 RIC regimen and may become a new standard of care RIC regimen for allotransplanted AML patients. A prospective phase 3 randomized study is warranted.
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- 2016
23. Sequential allogeneic hematopoietic stem cell transplantation for active refractory/relapsed myeloid malignancies: results of a reduced-intensity conditioning preceded by clofarabine and cytosine arabinoside, a retrospective study on behalf of the SFGM-TC.
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Le Bourgeois, Amandine, Labopin, Myriam, Marçais, Ambroise, de Latour, Regis Peffault, Blaise, Didier, Chantepie, Sylvain, N'Guyen, Stéphanie, Maillard, Natacha, Forcade, Edouard, Yakoub-Agha, Ibrahim, Huynh, Anne, Marchand, Tony, Bilger, Karin, Ceballos, Patrice, Charbonnier, Amandine, Turlure, Pascal, Rubio, Marie-Thérese, Béné, Marie Christine, Guillaume, Thierry, and Mohty, Mohamad
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HEMATOPOIETIC stem cell transplantation ,STEM cell transplantation ,ACUTE myeloid leukemia ,MYELOPROLIFERATIVE neoplasms ,HEMATOLOGIC malignancies ,MYELODYSPLASTIC syndromes treatment ,ACUTE myeloid leukemia treatment ,MYELODYSPLASTIC syndromes ,RESEARCH ,HOMOGRAFTS ,CLINICAL trials ,RESEARCH methodology ,IMMUNOSUPPRESSION ,ANTINEOPLASTIC agents ,PROGNOSIS ,RETROSPECTIVE studies ,EVALUATION research ,MEDICAL cooperation ,COMPARATIVE studies ,CYTARABINE - Abstract
Allogeneic stem cell transplantation (allo-SCT) represents the most beneficial treatment for patients with active relapsed/refractory (R/R) hematologic malignancies. Recently, sequential regimens combining debulking chemotherapy followed by reduced-intensity conditioning (RIC) have shown encouraging results for these patients. In this retrospective study, we report the extended results of a sequential regimen of clofarabine, cytosine arabinoside, and RIC in 131 adults with active R/R myeloid disease at transplant. Conditioning consisted of clofarabine (30 mg/m2/day) and cytosine arabinoside (1 g/m2/day) for 5 days, followed, after a rest of 3 days, by an RIC combining cyclophosphamide (60 mg/kg) for 1 day, iv busulfan (3.2 mg/kg/day) for 2 days, and anti-thymocyte globulin (2.5 mg/kg/day) for 2 days. Between 2007 and 2016, 131 patients (males n = 75, median age: 52.6 years) were identified from the SFGM-TC registry. There were 111 acute myeloid leukemia (AML) patients and 20 cases with myelodysplastic or myeloproliferative syndrome. Status at transplant was known for all but 4 patients and was primary refractory (n = 81) and 1st or 2nd relapse (n = 46). All patients received allo-SCT from a matched donor (sibling n = 64, unrelated n = 67). Engraftment was observed in 105/122 (86%) evaluable cases and 63% of the patients achieved complete remission (CR) after transplant. The 1-year overall survival, disease-free survival, relapse incidence, non-relapse mortality, and graft-versus-host disease-free/relapse-free survival were 39.2%, 28.1%, 41.0%, 30.8%, and 22.2%, respectively. This study confirms that this sequential clofarabine-based regimen provides a high CR rate in this critical population, although relapse remains a matter of concern. [ABSTRACT FROM AUTHOR]
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- 2020
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24. Post-transplant cyclophosphamide after matched sibling, unrelated and haploidentical donor transplants in patients with acute myeloid leukemia: a comparative study of the ALWP EBMT.
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Sanz, Jaime, Galimard, Jacques-Emmanuel, Labopin, Myriam, Afanasyev, Boris, Angelucci, Emanuele, Ciceri, Fabio, Blaise, Didier, Cornelissen, Jan J., Meijer, Ellen, Diez-Martin, J. L., Koc, Yener, Rovira, Montserrat, Castagna, Luca, Savani, Bipin, Ruggeri, Annalisa, Nagler, Arnon, and Mohty, Mohamad
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ACUTE myeloid leukemia ,TRANSPLANTATION of organs, tissues, etc. ,STEM cell transplantation ,GRAFT versus host disease ,SIBLINGS - Abstract
Background: The use of post-transplant cyclophosphamide (PTCy) is highly effective in preventing graft-versus-host disease (GVHD) in the haploidentical (Haplo) transplant setting and is being increasingly used in matched sibling (MSD) and matched unrelated (MUD) transplants. There is no information on the impact of donor types using homogeneous prophylaxis with PTCy. Methods: We retrospectively compared outcomes of adult patients with acute myeloid leukemia (AML) in first complete remission (CR1) who received a first allogeneic stem cell transplantation (SCT) with PTCy as GVHD prophylaxis from MSD (n = 215), MUD (n = 235), and Haplo (n = 789) donors registered in the EBMT database between 2010 and 2017. Results: The median follow-up was 2 years. Haplo-SCT carried a significantly increased risk of acute grade II–IV GVHD (HR 1.6; 95% CI 1.1–2.4) and NRM (HR 2.6; 95% CI 1.5–4.5) but a lower risk of relapse (HR 0.7; 95% CI 0.5–0.9) that translated to no differences in LFS (HR 1.1; 95% CI 0.8–1.4) or GVHD/relapse-free survival (HR 1; 95% CI 0.8–1.3). Interestingly, the use of peripheral blood was associated with an increased risk of acute (HR 1.9; 95% CI 1.4–2.6) and chronic GVHD (HR 1.7; 95% CI 1.2–2.4) but a lower risk of relapse (HR 0.7; 95% CI 0.5–0.9). Conclusions: The use of PTCy in patients with AML in CR1 receiving SCT from MSD, MUD, and Haplo is safe and effective. Haplo-SCT had increased risk of acute GVHD and NRM and lower relapse incidence but no significant difference in survival. [ABSTRACT FROM AUTHOR]
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- 2020
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25. Inferior outcome of allogeneic stem cell transplantation for secondary acute myeloid leukemia in first complete remission as compared to de novo acute myeloid leukemia.
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Schmaelter, Ann-Kristin, Labopin, Myriam, Socié, Gerard, Itälä-Remes, Maija, Blaise, Didier, Yakoub-Agha, Ibrahim, Forcade, Edouard, Cornelissen, Jan, Ganser, Arnold, Beelen, Dietrich, Labussière-Wallet, Hélène, Passweg, Jakob, Savani, Bipin N., Schmid, Christoph, Nagler, Arnon, and Mohty, Mohamad
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CANCER chemotherapy ,BLOOD diseases ,ACUTE myeloid leukemia ,GRAFT versus host disease ,STEM cell transplantation - Abstract
Following chemotherapy, secondary acute myeloid leukemia (sAML), occurring after antecedent hematologic diseases, previous chemotherapy or radiation, has an inferior prognosis compared with de novo AML. To define the outcome of sAML in the context of allogeneic stem cell transplantation (alloSCT), a retrospective, registry-based comparison was performed, including 11,439 patients with de novo and 1325 with sAML. Among transplants in first complete remission (CR1) (n = 8,600), the 3-year cumulative incidence of relapse (RI) and non-relapse mortality (NRM) was 28.5% and 16.4% for de novo, and 35% and 23.4% for sAML. Three-year overall survival (OS), leukemia-free survival (LFS) and Graft-versus-Host Disease/relapse-free survival (GRFS) was 60.8%, 55.1%, and 38.6% for de novo, and 46.7%, 41.6%, and 28.4% for sAML, respectively. In multivariate analysis, sAML was associated with a lower OS (HR = 1.33 [95% CI = 1.21–1.48]; p < 10
−5 ), LFS (HR = 1.32 [95% CI = 1.19–1.45]; p < 10−5 ) and GRFS (HR = 1.2 [95% CI = 1.1–1.31]; p < 10−4 ) and higher NRM (HR = 1.37 [95% CI = 1.17–1.59]; p < 10−4 ) and RI (HR = 1.27 [95% CI = 1.12–1.44]; p < 10−3 ). Results of the Cox model were confirmed in a matched-pair analysis. In contrast, results did not differ between de novo and sAML after alloSCT in induction failure or relapse. Hence, this analysis identified sAML as an independent risk factor for outcome after alloSCT in CR1. [ABSTRACT FROM AUTHOR]- Published
- 2020
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26. Stem cell transplantation from a haploidentical donor versus a genoidentical sister for adult male patients with acute myelogenous leukemia in first remission: A retrospective study from the acute leukemia working party of the European Society for Blood and Marrow Transplantation.
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Gorin, Norbert‐Claude, Labopin, Myriam, Blaise, Didier, Groot, Marco, Socié, Gerard, Bourhis, Jean Henri, Ciceri, Fabio, Polge, Emmanuelle, Nagler, Arnon, Mohty, Mohamad, Gorin, Norbert-Claude, and de Groot, Marco
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ACUTE myeloid leukemia ,STEM cell transplantation ,ACUTE leukemia ,TRANSPLANTATION of organs, tissues, etc. ,BONE marrow - Abstract
Background: In adult patients with acute myeloid leukemia (AML), a matched sibling donor (MSD) is considered the first choice for an allogeneic transplantation. However, a female donor for a male recipient is a poor prognostic factor. The authors compared haploidentical (HAPLO) donors with female MSDs.Methods: In total, 834 men underwent allogenic transplantation from a female MSD, and 232 men underwent allogenic transplantation from a HAPLO donor. Of these, 86% of HAPLO recipients and 3% of MSD recipients received graft-versus-host disease (GVHD) prophylaxis posttransplantation with high-dose cyclophosphamide. A significant qualitative interaction was observed between donor type and cytogenetics, Therefore, the analyses were stratified on cytogenetics.Results: Of the men with intermediate-risk AML, 638 received transplantation from a female MSD, and 160 received transplantation from a HAPLO donor. In multivariate analysis, poor risk factors were a HAPLO donor versus an MSD for nonrelapse mortality (hazard ratio [HR], 1.7; P = .02) and patient age for nonrelapse mortality and overall survival (HR, 1.22 [P = .02] and 1.15 [P = .02], respectively). HAPLO transplantation resulted in less chronic GVHD (HR, 0.43; P < 10-4 ) but lower leukemia-free survival (HR, 1.7; P = .04). The GVHD/relapse-free survival (GRFS) was not different. Of the men with high-risk AML, 196 received transplantation from a female MSD, and 72 received transplantation from a HAPLO donor. By multivariate analysis, HAPLO recipients had a lower incidence of relapse (HR, 0.40; P = .004), better leukemia-free survival (HR, 0.46; P = .003), better overall survival (HR, 0.43; P = .003), and better GRFS (HR, 0.54; P = .006).Conclusions: In men who have intermediate-risk AML, allogenic transplantation from a sister MSD or a HAPLO donor produces similar GRFS. However, in men who have high-risk AML, a HAPLO donor combined with prophylactic high-dose cyclophosphamide posttransplantation may be a better choice. [ABSTRACT FROM AUTHOR]- Published
- 2020
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27. Individualized prediction of leukemia-free survival after autologous stem cell transplantation in acute myeloid leukemia.
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Shouval, Roni, Labopin, Myriam, Gorin, Norbert C., Bomze, David, Houhou, Mohamed, Blaise, Didier, Zuckerman, Tsila, Baerlocher, Gabriela M., Capria, Saveria, Forcade, Edouard, Huynh, Anne, Saccardi, Riccardo, Martino, Massimo, Schaap, Michel, Wu, Depei, Mohty, Mohamad, and Nagler, Arnon
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STEM cell transplantation ,ACUTE myeloid leukemia ,RECEIVER operating characteristic curves ,PROTEIN-tyrosine kinases - Abstract
Background: Autologous stem cell transplantation (ASCT) is a potential consolidation therapy for acute myeloid leukemia (AML). This study was designed to develop a prediction model for leukemia-free survival (LFS) in a cohort of patients with de novo AML treated with ASCT during their first complete remission.Methods: This was a registry study of 956 patients reported to the European Society for Blood and Marrow Transplantation. The primary outcome was LFS. Multivariate Cox regression modeling with backward selection was used to select variables for the construction of the nomogram. The nomogram's performance was evaluated with discrimination (the area under the receiver operating characteristic curve [AUC]) and calibration.Results: Age and cytogenetic risk (with or without FMS-like tyrosine kinase 3 internal tandem duplication) were predictive of LFS and were used for the construction of the nomogram. Each factor in the nomogram was ascribed points according to its predictive weight. Through the calculation of the total score, the probability of LFS at 1, 3, and 5 years for each patient could be estimated. The discrimination of the nomogram, measured as the AUC, was 0.632 (95% confidence interval [CI], 0.595-0.669), 0.670 (95% CI, 0.635-0.705), and 0.687 (95% CI, 0.650-0.724), respectively. Further validation with bootstrapping showed similar AUCs (0.629 [95% CI, 0.597-0.657], 0.667 [95% CI, 0.633-0.699], and 0.679 [95% CI, 0.647-0.712], respectively), and this suggested that the model was not overfitted. Calibration was excellent. Patients were stratified into 4 incremental 5-year prognostic groups, with the probabilities of LFS and overall survival ranging from 25% to 64% and from 33% to 79%, respectively.Conclusions: The Auto-AML nomogram score is a tool integrating individual prognostic factors to provide a probabilistic estimation of LFS after ASCT for patients with AML. [ABSTRACT FROM AUTHOR]- Published
- 2019
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28. Impact of conditioning intensity on outcomes of haploidentical stem cell transplantation for patients with acute myeloid leukemia 45 years of age and over.
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Santoro, Nicole, Labopin, Myriam, Ciceri, Fabio, Van Lint, Maria Teresa, Nasso, Daniela, Blaise, Didier, Arcese, William, Tischer, Johanna, Bruno, Benedetto, Ehninger, Gerhard, Koc, Yener, Santarone, Stella, Huang, Xiao‐Jun, Savani, Bipin N., Mohty, Mohamad, Ruggeri, Annalisa, Nagler, Arnon, and Huang, Xiao-Jun
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ACUTE myeloid leukemia ,STEM cell transplantation ,GRAFT versus host disease ,STEM cells ,BLOOD cells ,ACUTE myeloid leukemia treatment ,GRAFT versus host disease prevention ,ACUTE myeloid leukemia diagnosis ,AGE distribution ,HEMATOPOIETIC stem cell transplantation ,IMMUNOSUPPRESSION ,IMMUNOSUPPRESSIVE agents ,PROGNOSIS ,TREATMENT effectiveness ,ACQUISITION of data ,RETROSPECTIVE studies ,IMPACT of Event Scale - Abstract
Background: T cell-replete haploidentical stem cell transplantation (haplo-SCT) is a valid therapeutic option for adult patients with high-risk acute myeloid leukemia (AML) lacking an HLA-matched sibling or unrelated donor.Method: We retrospectively analyzed the outcomes of 912 AML patients ≥45 years of age who had undergone haplo-SCT with either myeloablative conditioning (MAC; n = 373) or reduced intensity conditioning (RIC; n = 539) regimens.Results: The median follow-up was 31.1 and 25.7 months for MAC and RIC, respectively. The incidence of relapse and nonrelapse mortality (NRM) were 25.1% versus 28.7% and 31.0% versus 30.3% for MAC and RIC, respectively; 2-year leukemia-free survival (LFS) was 43.9% for MAC versus 41.0% for RIC. In multivariate analysis, the use of MAC versus RIC was not associated with a difference in the outcomes. Results were confirmed in the propensity score-weighted analysis. Disease status and performance status at transplantation were associated with outcomes. Notably, the use of posttransplantation cyclophosphamide was associated with reduced acute graft-versus-host disease (aGVHD) stage III-IV, and NRM and increased overall survival, LFS, and GVHD-free, relapse-free survival. The use of mobilized peripheral blood stem cells was associated with an increased risk of stage II-IV aGVHD.Conclusion: No differences were found between MAC and RIC regimens for haplo-SCT in adults with AML who were ≥45 years of age. The type of GVHD prophylaxis, disease status, and performance status were the major predictors of transplantation outcome. These results may serve as the background for randomized study comparing RIC versus MAC for haplo-SCT in adults with AML. [ABSTRACT FROM AUTHOR]- Published
- 2019
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29. Relapse and survival after transplantation for complex karyotype acute myeloid leukemia: A report from the Acute Leukemia Working Party of the European Society for Blood and Marrow Transplantation and the University of Texas MD Anderson Cancer Center.
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Ciurea, Stefan O., Labopin, Myriam, Socie, Gerard, Volin, Liisa, Passweg, Jakob, Chevallier, Patrice, Beelen, Dietrich, Milpied, Noel, Blaise, Didier, Cornelissen, Jan J., Fegueux, Nathalie, Polge, Emmanuelle, Kongtim, Piyanuch, Rondon, Gabriela, Esteve, Jordi, Mohty, Mohamad, Savani, Bipin N., Champlin, Richard E., and Nagler, Arnon
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ACUTE myeloid leukemia treatment ,KARYOTYPES ,CANCER relapse ,CANCER patients ,HEMATOPOIETIC stem cell transplantation - Abstract
Background: Despite recent advances in allogeneic hematopoietic stem cell transplantation (AHSCT), the outcome of patients who have acute myeloid leukemia (AML) with a complex karyotype (CK) remains poor. The objective of this study was to identify prognostic factors associated with post-transplantation survival in a large cohort of patients with CK AML.Methods: In total, data on 1342 consecutively patients who underwent transplantation for CK (≥3 chromosomal abnormalities) AML were provided by the Acute Leukemia Working Party of the European Society for Blood and Marrow Transplantation and from the University of Texas MD Anderson Cancer Center database were included in the analysis. The median patient age was 52 years. The donors were human leukocyte antigen-matched related donors (N = 749), matched unrelated donors (N = 513), and mismatched unrelated donors (N = 80).Results: Relapse was the main cause of treatment failure. Overall, 51% of patients relapsed, 17.6% died of treatment-related mortality, and 31.3% survived leukemia-free. In multivariate analysis, the factors associated with an increased risk of relapse were age (>40 years; hazard ratio [HR], 1.1 per 10 years; P = .02), secondary AML (HR, 1.35; P = .01), active disease at transplantation (HR, 1.98; P < .001), and deletion/monosomy 5 (HR, 1.5; P < .001); whereas age (HR, 1.15 per 10 years; P < .001), secondary AML (HR, 1.36; P = .001), active disease at transplantation (HR, 1.99; P < .001), deletion/monosomy 5 (HR, 1.24; P = .008), and deletion/monosomy 7 (HR, 1.44; P < .001) predicted for leukemia-free survival.Conclusions: Disease relapse remains the most common cause of treatment failure for patients with CK AML after transplantation. Novel approaches to decrease the relapse rate and improve survival are needed in these patients. Cancer 2018;124:2134-41. © 2018 American Cancer Society. [ABSTRACT FROM AUTHOR]- Published
- 2018
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30. Autologous stem cell transplantation for adult acute myelocytic leukemia in first remission-Better outcomes after busulfan and melphalan compared with busulfan and cyclophosphamide: A retrospective study from the Acute Leukemia Working Party of the European Society for Blood and Marrow Transplantation (EBMT)
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Gorin, Norbert‐Claude, Labopin, Myriam, Czerw, Tomasz, Pabst, Thomas, Blaise, Didier, Dumas, Pierre‐Yves, Nemet, Damir, Arcese, William, Trisolini, Silvia Maria, Wu, Depei, Huynh, Anne, Zuckerman, Tsila, Meijer, Ellen, Cagirgan, Seckin, Cornelissen, Jan, Houhou, Mohamed, Polge, Emmanuelle, Mohty, Mohamad, and Nagler, Arnon
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STEM cell transplantation ,ACUTE myeloid leukemia ,BUSULFAN ,MELPHALAN ,CYCLOPHOSPHAMIDE ,RETROSPECTIVE studies - Abstract
BACKGROUND Autologous stem cell transplantation (ASCT) for adult acute myelogenous leukemia (AML) is a valid therapeutic option for patients with good-risk and intermediate-risk disease. The authors used the registry of the European Society for Blood and Marrow Transplantation to compare combined busulfan and melphalan (BUMEL) with combined busulfan and cyclophosphamide (BUCY) before transplantation. METHODS From 2005 to 2013, 853 patients with available cytogenetics underwent ASCT in first remission, including 257 after receiving BUMEL and 596 after receiving BUCY. The proportion of patients with good-risk AML was lower in those who received BUMEL (14% vs 20%; P = .02). More patients who received BUMEL underwent autograft in molecular remission (89% vs 78%; P = .02). Three years after transplantation, the relapse incidence (RI) was 48.7%, the leukemia-free survival (LFS) rate was 47.7%, the overall survival (OS) rate was 66.2%, and the nonrelapse mortality (NRM) rate was 3.6%. RESULTS Patients who underwent an autograft after receiving BUMEL fared better than those who underwent an autograft after receiving BUCY with a lower RI (39.5% vs 52.2%; hazard ratio [HR], 0.65; 95% confidence interval [CI], 0.49-0.87; P = .003) a better LFS (55.4% vs 44.6%; HR, 0.69; 95% CI, 0.53-0.89; P = .005), and a better OS (73.8% vs 63%; HR, 0.62; 95% CI, 0.47-0.82; P = .0007). There was no difference in the NRM rate (BUMEL vs BUCY, 4.5% vs 3.2%, respectively). Among 74 patients in the BUMEL group and 187 in the BUCY group who underwent autograft in molecular remission, the RI was 30% versus 51%, respectively (univariate analysis; P = .01), and the LFS rate was 66% versus 47%, respectively (univariate analysis; P = .03). CONCLUSIONS In patients with AML in first complete remission who undergo ASCT, the BUMEL combination is a better preparative regimen. Cancer 2017;123:824-31. © 2016 American Cancer Society. [ABSTRACT FROM AUTHOR]
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- 2017
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31. Impact of in vivo T cell depletion in HLA-identical allogeneic stem cell transplantation for acute myeloid leukemia in first complete remission conditioned with a fludarabine iv-busulfan myeloablative regimen: a report from the EBMT Acute Leukemia Working Party.
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Rubio, Marie Thérèse, D'Aveni-Piney, Maud, Labopin, Myriam, Hamladji, Rose-Marie, Sanz, Miguel A., Blaise, Didier, Ozdogu, Hakan, Daguindeau, Etienne, Richard, Carlos, Santarone, Stella, Irrera, Giuseppe, Yakoub-Agha, Ibrahim, Yeshurun, Moshe, Diez-Martin, Jose L., Mohty, Mohamad, Savani, Bipin N., and Nagler, Arnon
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T cells ,FLUDARABINE ,BUSULFAN ,ACUTE myeloid leukemia ,MYELOSUPPRESSION - Abstract
Background: The impact of the use of anti-thymocyte globulin (ATG) in allogeneic stem cell transplantation performed with HLA-identical sibling donors following fludarabine and 4 days intravenous busulfan myeloablative conditioning regimen has been poorly explored. Methods: We retrospectively analyzed 566 patients who underwent a first HLA-identical allogeneic stem cell transplantation with this conditioning regimen for acute myeloid leukemia in first complete remission between 2006 and 2013 and compared the outcomes of 145 (25.6%) patients who received ATG (ATG group) to 421 (74.4%) who did not (no-ATG group). The Kaplan-Meier estimator, the cumulative incidence function, and Cox proportional hazards regression models were used where appropriate. Results: Patients in the ATG group were older, received more frequently peripheral blood stem cell grafts from older donors, and were transplanted more recently. With a median follow-up of 19 months, patients in the ATG group had reduced 2-year cumulative incidence of chronic graft-versus-host disease (GVHD) (31 vs. 52%, p = 0.0002) and of its extensive form (8 vs. 26%, p < 0.0001) but similar relapse incidence (22 vs. 27%, p = 0.23) leading to improved GVHD and relapse-free survival (GRFS) (60 vs. 40%, p = 0.0001). In multivariate analyses, the addition of ATG was independently associated with lower chronic GVHD (HR = 0.46, p = 0.0001), improved leukemia-free survival (HR = 0.67, p = 0.027), overall survival (HR = 0.65, p = 0.027), and GRFS (HR = 0.51, p=4 x 10
-5 ). Recipient age above 50 years was the only other factor associated with worse survivals. Conclusions: These results suggest that the use of ATG with fludarabine and 4 days intravenous busulfan followed by HLA-identical sibling donor allogeneic stem cell transplantation for acute myeloid leukemia improves overall transplant outcomes due to reduced incidence of chronic GVHD without increased relapse risk. [ABSTRACT FROM AUTHOR]- Published
- 2017
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32. Allogeneic stem cell transplantation in adult patients with acute myeloid leukaemia and 17p abnormalities in first complete remission: a study from the Acute Leukemia Working Party (ALWP) of the European Society for Blood and Marrow Transplantation (EBMT)
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Poiré, Xavier, Labopin, Myriam, Maertens, Johan, Yakoub-Agha, Ibrahim, Blaise, Didier, Ifrah, Norbert, Socié, Gérard, Gedde-Dhal, Tobias, Schaap, Nicolaas, Cornelissen, Jan J., Vigouroux, Stéphane, Sanz, Jaime, Michaux, Lucienne, Esteve, Jordi, Mohty, Mohamad, and Nagler, Arnon
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STEM cell transplantation ,ACUTE myeloid leukemia ,DISEASE remission ,PROGNOSIS ,TREATMENT effectiveness ,THERAPEUTICS - Abstract
Background: Acute myeloid leukaemia (AML) with 17p abnormalities (abn(17p)) carries a very poor prognosis due to high refractoriness to conventional chemotherapy, and allogeneic stem cell transplantation (allo-SCT) appears as the only potential curative option. Methods: To address outcomes after allo-SCT in patients with abn(17p), we retrospectively analysed de novo or secondary AML undergoing SCT between 2000 and 2013 from the EBMT registry. Results: One hundred thirty-nine patients with confirmed abn(17p) have been selected. At the time of transplant, one hundred twenty-five were in first remission (CR1). Median age was 54 years old. Abn(17p) was associated with a monosomal karyotype in 83% of patients, complex karyotype in 91%, monosomy 5 or 5q deletion (-5/5q-) in 55%, monosomy 7 (-7) in 39% and both -5/5q and -7 in 27%. Seventy-three patients (59%) had a reduced-intensity conditioning regimen. The 2-year overall survival (OS) and leukaemia-free survival (LFS) were 28 and 24%, respectively. The 2-year non-relapse mortality (NRM) was 15%, and 2-year relapse incidence (RI) was 61%. The cumulative incidence of grade II to IV acute graft-versus-host disease (GvHD) was 24% and that of chronic GvHD was 21%. In multivariate analysis, the presence of a -5/5q- in addition to abn(17p) was significantly and independently associated with worse OS, LFS and higher RI. Age and donor types did not correlate with outcome. Conditioning intensity was not statistically associated with OS, LFS and NRM when adjusted for patients’ age. Conclusions: In contrast to the dismal prognosis reported for AML patients harbouring abn(17p) undergoing conventional chemotherapy, allogeneic SCT provides responses in about 25% of those patients transplanted in CR1. [ABSTRACT FROM AUTHOR]
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- 2017
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33. Matched and mismatched unrelated donor compared to autologous stem cell transplantation for acute myeloid leukemia in first complete remission: a retrospective, propensity score-weighted analysis from the ALWP of the EBMT.
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Saraceni, Francesco, Labopin, Myriam, Gorin, Norbert-Claude, Blaise, Didier, Tabrizi, Reza, Volin, Liisa, Cornelissen, Jan, Cahn, Jean-Yves, Chevallier, Patrice, Craddock, Charles, Depei Wu, Huynh, Anne, Arcese, William, Mohty, Mohamad, and Nagler, Arnon
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STEM cell transplantation ,ACUTE myeloid leukemia ,DISEASE remission ,GRAFT versus host disease ,HEMATOLOGIC malignancies ,CANCER ,LYMPHOMAS - Abstract
Background: Optimal post-remission strategy for patients with acute myeloid leukemia (AML) is matter of intense debate. Recent reports have shown stronger anti-leukemic activity but similar survival for allogeneic stem cell transplantation (allo-HSCT) from matched sibling donor compared to autologous transplantation (auto-HSCT); however, there is scarcity of literature confronting auto-HSCT with allo-HSCT from unrelated donor (UD-HSCT), especially mismatched UD-HSCT. Methods: We retrospectively compared outcome of allogeneic transplantation from matched (10/10 UD-HSCT) or mismatched at a single HLA-locus unrelated donor (9/10 UD-HSCT) to autologous transplantation in patients with AML in first complete remission (CR1). A total of 2879 patients were included; 1202 patients received auto-HSCT, 1302 10/10 UD-HSCT, and 375 9/10 UD-HSCT. A propensity score-weighted analysis was conducted to control for disease risk imbalances between the groups. Results: Matched 10/10 UD-HSCT was associated with the best leukemia-free survival (10/10 UD-HSCT vs auto-HSCT: HR 0.7, p = 0.0016). Leukemia-free survival was not statistically different between auto-HSCT and 9/10 UD-HSCT (9/10 UD-HSCT vs auto-HSCT: HR 0.8, p = 0.2). Overall survival was similar across the groups (10/10 UD-HSCT vs auto-HSCT: HR 0.98, p = 0.84; 9/10 UD-HSCT vs auto-HSCT: HR 1.1, p = 0.49). Notably, in intermediate-risk patients, OS was significantly worse for 9/10 UD-HSCT (9/10 UD-HSCT vs auto-HSCT: HR 1.6, p = 0.049), while it did not differ between auto-HSCT and 10/10 UD-HSCT (HR 0.95, p = 0.88). In favorable risk patients, auto-HSCT resulted in 3-year LFS and OS rates of 59 and 78 %, respectively. Conclusions: Our findings suggest that in AML patients in CR1 lacking an HLA-matched sibling donor, 10/10 UD-HSCT significantly improves LFS, but this advantage does not translate in better OS compared to auto-HSCT. In intermediate-risk patients lacking a fully HLA-matched donor, auto-HSCT should be considered as a valid option, as better survival appears to be provided by auto-HSCT compared to mismatched UD-HSCT. Finally, auto-HSCT provided an encouraging outcome in patients with favorable risk AML. [ABSTRACT FROM AUTHOR]
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- 2016
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34. Long-term follow-up of patients with acute myeloid leukemia surviving and free of disease recurrence for at least 2 years after autologous stem cell transplantation: A report from the Acute Leukemia Working Party of the European Society for Blood and Marrow Transplantation.
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Czerw, Tomasz, Labopin, Myriam, Gorin, Norbert‐Claude, Giebel, Sebastian, Blaise, Didier, Meloni, Giovanna, Pigneux, Arnaud, Bosi, Alberto, Veelken, Joan, Ferrara, Felicetto, Schaap, Nicolaas, Lemoli, Roberto M., Cornelissen, Jan J., Beohou, Eric, Nagler, Arnon, and Mohty, Mohamad
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ACUTE myeloid leukemia ,CANCER patients ,CANCER relapse ,AUTOTRANSPLANTATION ,STEM cell transplantation ,MORTALITY - Abstract
Background: Leukemia recurrence is a major cause of treatment failure after autologous stem cell transplantation for acute myeloid leukemia (AML). It usually occurs within the first 2 years after transplantation. The goal of the current retrospective study was to assess the follow-up of and characterize risk factors for outcome among patients who survived free of disease recurrence after this period.Methods: The analysis included 3567 adults (median age, 45 years) with AML who underwent autografting during the first (86% of patients) or second (14% of patients) complete remission between 1990 and 2008. The stem cell source was the bone marrow in 32% of patients or the peripheral blood in 68% of patients. The median follow-up was 6.9 years.Results: At 5 years and 10 years after transplantation, the probability of leukemia-free survival was 86% and 76%, respectively; the recurrence incidence was 11% and 16%, respectively; and the nonrecurrence mortality rate was 3% and 8%, respectively. The observed survival was decreased compared with the expected survival of the general European population. In a multivariate analysis, decreased probability of leukemia-free survival was demonstrated for patients who underwent peripheral blood autologous stem cell transplantation; had French-American-British subtypes M0, M6, or M7; and were of an older age. The same factors were found to be associated with an increased risk of disease recurrence. Nonrecurrence mortality was found to be affected by older age.Conclusions: The results of the current analysis indicate that late recurrences remain a major concern after autologous stem cell transplantation among patients with AML, indicating the need for close monitoring of minimal residual disease and additional leukemic control measures after transplantation. Cancer 2016;122:1880-7. © 2016 American Cancer Society. [ABSTRACT FROM AUTHOR]- Published
- 2016
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35. Hematopoietic stem cell transplantation for patients with AML in first complete remission.
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Cornelissen, Jan J. and Blaise, Didier
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HEMATOPOIETIC stem cell transplantation , *ACUTE myeloid leukemia , *DISEASE relapse , *PROTEIN-tyrosine kinases , *GRAFT versus host disease - Abstract
Postremission therapy in patients with acute myeloid leukemia (AML) may consist of continuing chemotherapy or transplantation using either autologousor allogeneic stem cells. Patients with favorable subtypes of AML generally receive chemotherapeutic consolidation, although recent studies have also suggested favorable outcome after hematopoietic stem cell transplantation (HSCT). Although allogeneic HSCT (alloHSCT) is considered the preferred type of postremission therapy in poor- and very-poor-risk AML, the place of alloHSCT in intermediate-risk AML is being debated, and autologous HSCT is considered a valuable alternative that may be preferred in patients withoutminimal residual disease after induction chemotherapy. Here, we review postremission transplantation strategies using either autologous or allogeneic stem cells. Recent developments in the field of alternative donors, including cord blood and haploidentical donors, are highlighted, and we discuss reduced-intensity alloHSCT in older AML recipients who represent the predominant category of patients with AML who have a high risk of relapse in first remission. [ABSTRACT FROM AUTHOR]
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- 2016
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36. Increased NK cell maturation in patients with acute myeloid leukemia.
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Chretien, Anne-Sophie, Granjeaud, Samuel, Gondois-Rey, Françoise, Harbi, Samia, Orlanducci, Florence, Blaise, Didier, Vey, Norbert, Arnoulet, Christine, Fauriat, Cyril, Olive, Daniel, Ullrich, Evelyn, and Guerra, Nadia
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KILLER cells ,ACUTE myeloid leukemia ,FLOW cytometry - Abstract
The article provides information on a study which discussed the application of natural killer (NK) cell maturation profiling in healthy volunteers (HV) and patients with acute myeloid leukemia (AML) using automated analysis of flow cytometry data.
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- 2015
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37. Comparison of umbilical cord blood allogeneic stem cell transplantation vs. auto- SCT for adult acute myeloid leukemia patients in second complete remission at transplant: a retrospective study on behalf of the SFGM- TC.
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Chevallier, Patrice, Labopin, Myriam, Socie, Gerard, Rubio, Marie‐There, Blaise, Didier, Vigouroux, Stephane, Huynh, Anne, Michallet, Mauricette, Bay, Jacques‐Olivier, Maury, Sébastien, Yakoub‐Agha, Ibrahim, Fegueux, Nathalie, Deconinck, Eric, Contentin, Nathalie, Maillard, Natacha, Bulabois, Claude‐Eric, Francois, Sylvie, Oumedaly, Reman, Raus, Nicole, and Mohty, Mohamad
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ACUTE myeloid leukemia ,CYTOGENETICS ,STEM cells ,MULTIVARIATE analysis ,HOMOGRAFTS - Abstract
This retrospective study considered the outcomes of 181 patients with acute myeloid leukemia ( AML) transplanted in second complete remission ( CR2) between January 2005 and April 2012 and who received either a myeloablative autologous stem cell transplant (Auto- SCT; n = 82; median age: 48 years; median follow-up: 45 months) or an umbilical cord blood ( UCB) allogeneic SCT ( n = 99, median age: 46 years; median follow-up: 36 months; conditioning regimens: myeloablative n = 21, reduced n = 78; single unit n = 37, double units n = 62). Although the Auto group showed a significant better prognostic profile at transplant, with longer median interval between diagnosis and time of graft, higher incidence of good-risk cytogenetics and lower number of previously transplanted patients, 3-year OS and LFS were similar between both groups (Auto: 59 ± 6% vs. 50 ± 6%, P = 0.45; and 57 ± 6% vs. 46 ± 6%, P = 0.37). In multivariate analysis, UCB allo- SCT was associated with lower relapse incidence ( HR: 0.3, 95% CI: 0.11-0.82, P = 0.02), but higher non-relapse mortality ( NRM) ( HR: 4.16; 95% CI: 1.46-11.9, P = 0.008). Results from this large study suggest that UCB allo- SCT provides better disease control than auto- SCT, which is especially important in the setting of high-risk disease. However, this disease control advantage is counterbalanced by higher toxicity, highlighting the need for novel approaches aiming to decrease NRM after UCB allo- SCT. [ABSTRACT FROM AUTHOR]
- Published
- 2015
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38. Impact of postremission consolidation chemotherapy on outcome after reduced-intensity conditioning allogeneic stem cell transplantation for patients with acute myeloid leukemia in first complete remission: A report from the Acute Leukemia Working Party of the European Group for Blood and Marrow Transplantation
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Yeshurun, Moshe, Labopin, Myriam, Blaise, Didier, Cornelissen, Jan J., Sengeloev, Henrik, Vindelov, Lars, Kuball, Juergen, Chevallier, Patrice, Craddock, Charles, Socie, Gerard, Bilger, Karin, Schouten, Harry C., Fegueux, Nathalie, Goker, Hakan, Maertens, Johan, Bunjes, Donald, Arnold, Renate, Nagler, Arnon, and Mohty, Mohamad
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DRUG therapy ,STEM cell transplantation ,ACUTE myeloid leukemia treatment ,STEM cell treatment ,TRANSPLANTATION of organs, tissues, etc. - Abstract
BACKGROUND The objective of the current study was to investigate the role of postremission consolidation chemotherapy before reduced-intensity conditioning (RIC) allogeneic stem cell transplantation (alloSCT) for patients with acute myeloid leukemia (AML) in first complete remission (CR1). METHODS Of the 789 consecutive patients with AML in CR1 who underwent RIC alloSCT from a human leukocyte antigen-matched sibling or matched unrelated donor peripheral stem cell grafts between 2001 and 2010, 591 patients received at least 1 cycle of consolidation chemotherapy and 198 patients did not receive any consolidation chemotherapy before alloSCT. To minimize inherent survival bias in favor of patients who underwent transplant long after achieving CR1, the study focused on 373 patients who underwent transplant within the median time frame between achievement of CR1 and alloSCT (3 months for patients who underwent alloSCT from matched siblings and 4 months for patients who underwent alloSCT from matched unrelated donors). In this subgroup, 151 patients did not receive any consolidation chemotherapy and 222 patients received ≥ 1 consolidation chemotherapy cycle. RESULTS With a median follow-up of 36 months (range, 2 months-135 months), the 3-year cumulative recurrence incidence (RI) was not significantly different between the groups (36% ± 4% for the group treated without consolidation chemotherapy vs 38% ± 3% for patients who received consolidation chemotherapy; P = .89). In addition, leukemia-free survival was similar between the groups (45% ± 4% and 47% ± 3%, respectively; P = .41). Dose intensity of cytarabine given during consolidation chemotherapy appeared to have no influence on RI. On multivariate analysis, pretransplant consolidation (≥ 1 cycle vs 0 cycles) was found to have no significant impact on RI (hazards ratio, 1.29; 95% confidence interval, 0.84-1.97 [ P = .24]) or leukemia-free survival (hazards ratio, 1.00; 95% confidence interval, 0.71-1.42 [ P = .99]). CONCLUSIONS The data from the current study suggest no apparent advantage for postremission consolidation chemotherapy before RIC alloSCT, provided a donor is readily available. Cancer 2014;120:855-863. © 2013 American Cancer Society. [ABSTRACT FROM AUTHOR]
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- 2014
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39. Outcome of relapse after allogeneic stem cell transplant in patients with acute myeloid leukemia.
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Devillier, Raynier, Crocchiolo, Roberto, Etienne, Anne, Prebet, Thomas, Charbonnier, Aude, Fürst, Sabine, El-Cheikh, Jean, D'Incan, Evelyne, Rey, Jérôme, Faucher, Catherine, Blaise, Didier, and Vey, Norbert
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STEM cell transplantation research ,STEM cell research ,ACUTE myeloid leukemia ,SALVAGE therapy ,CANCER chemotherapy - Abstract
Although allogeneic stem cell transplant (Allo-SCT) is an effective treatment for high-risk acute myeloid leukemia (AML), relapses remain a major cause of treatment failure. There is currently no standard of care for post-transplant relapse of AML, but the increasing numbers of investigational agents in this setting require a better knowledge of their outcome. We retrospectively evaluated the efficacy of salvage therapies in 54 patients with AML relapsing after Allo-SCT. Twenty-four patients received intensive salvage treatment (17 non-intensive chemotherapy, 13 supportive care). Complete remissions (CRs) were seen only in the group who received intensive salvage (CR rate: 17/24 [71%]). One-year overall survival was 19% (median: 3.4 months) in the whole study group and 33% in the intensive savage group (vs. 7% for patients without intensive salvage, p = 0.004). Factors influencing overall survival (OS) were: time to relapse after Allo-SCT (hazard ratio [HR]: 3.7 [1.6-8.8]) and performance status (PS) at relapse (HR: 2.2 [1.1-4.4]) by multivariate analysis. Our results confirm the poor prognosis of AML relapse after Allo-SCT. In selected patients salvage chemotherapy produces CRs, but these are short lived. Other strategies aiming at modulating immune antileukemic activity have to be developed. [ABSTRACT FROM AUTHOR]
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- 2013
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40. Combination of cytarabine and topotecan in patients treated for acute myeloid leukemia with persistent disease after frontline induction.
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Prébet, Thomas, Jean, Estelle, Autret, Aurélie, Charbonnier, Aude, Rey, Jerome, Etienne, Anne, D'incan, Evelyne, Fürst, Sabine, Arnoulet, Christine, Blaise, Didier, and Vey, Norbert
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LEUKEMIA treatment ,MYELOID leukemia ,TOPOTECAN ,CYTARABINE ,CANCER chemotherapy ,CANCER relapse ,MULTIVARIATE analysis ,TREATMENT effectiveness - Abstract
After a first course of induction chemotherapy, 30-40% of patients with acute myeloid leukemia (AML) do not achieve a complete response (CR). A second course of an anthracycline and intermediate-dose cytarabine (IDAC) allows a significant number of patients with persistent AML at day 14 to finally achieve a CR. We hypothesized that use of a topotecan and cytarabine combination in this setting might improve tolerance and efficacy. Cytarabine (1000 mg/m
2 /12 h days 1-4) was combined with topotecan (TA, 1.25 mg/m2 /day by continuous intravenous infusion [CIV] days 1-4) in 31 consecutive patients with ≥ 5% marrow blasts by day 14 of induction. The median follow-up was 36 months. The CR rate was 81%, and the 2-year probability of overall survival and cumulative incidence of relapse were 66% and 38%, respectively. No unexpected toxicity was observed. Comparison with historical controls treated with the combination of a similar schedule of cytarabine and an anthracycline showed a better CR rate ( p = 0.054), overall survival ( p = 0.03) and cumulative incidence of relapse ( p = 0.03). These results were confirmed in a multivariate analysis model. This work shows that the substitution of an anthracycline by topotecan is feasible and associated with significant efficacy for patients with AML with persistent leukemia at day 14 after standard-dose anthracycline induction. [ABSTRACT FROM AUTHOR]- Published
- 2012
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41. Mobilized peripheral blood stem cells compared with bone marrow from HLA-identical siblings for reduced-intensity conditioning transplantation in acute myeloid leukemia in complete remission: a retrospective analysis from the Acute Leukemia Working Party of EBMT
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Nagler, Arnon, Labopin, Myriam, Shimoni, Avichai, Mufti, Ghulam J., Cornelissen, Jan J., Blaise, Didier, Janssen, Jeroen J. W. M., Milpied, Noel, Vindelov, Lars, Petersen, Eefke, Gribben, John, Bacigalupo, Andrea, Malm, Claes, Niederwieser, Dietger, Socié, Gerard J., Arnold, Renate, Brown, Paul, Goker, Hakan, Rocha, Vanderson, and Mohty, Mohamad
- Subjects
ACUTE myeloid leukemia ,STEM cell transplantation ,BONE marrow ,HISTOCOMPATIBILITY antigens ,ACUTE leukemia - Abstract
Reduced-intensity conditioning ( RIC)-allo SCT is increasingly used for acute myelogenous leukemia. Limited data are available for the comparison of peripheral blood stem cells with bone marrow for RIC-allo SCT. We used the European Group for Blood and Marrow Transplantation ( EBMT) ALWP data to compare the outcome of mobilized peripheral blood stem cells ( PBSC) ( n = 1430) vs. bone marrow ( BM) ( n = 107) for acute myelogenous leukemia ( AML) patients with complete remission that underwent RIC-allo SCT from compatible sibling donors. The leukemia features, the disease status, and the time from diagnosis were similar between the two groups. Engraftment was achieved in 99% and 93% in the PBSC and BM groups, respectively ( P < 0.0001). The day of engraftment was significantly earlier for the PBSC vs. the BM group, 15 (1-59) and 19 (5-69), respectively ( P < 0.001). Acute GVHD, severe GVHD (grade III-IV) and chronic GVHD did not differ between the groups. leukemia-free survival ( LFS), relapse, and non-relapsed mortality ( NRM) were 51 ± 2%, 32 ± 1%, and 17 ± 1% vs. 50 ± 6%, 38 ± 6%, and 12 ± 3% for the PBSC and BM groups, respectively. Our results indicate faster engraftment, but no difference in GVHD, LFS, relapse, and NRM when comparing PBSC to BM grafts from sibling donors following RIC conditioning. This is the first study comparing PBSC to BM grafts in the RIC setting, analyzing a homogeneous population of patients with AML in remission. Whether PBSC should be preferred for advanced phases of the disease, where the outcome is dominated by relapse incidences, needs further investigation. [ABSTRACT FROM AUTHOR]
- Published
- 2012
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42. Improved outcome of patients with low- and intermediate-risk cytogenetics acute myeloid leukemia (AML) in first relapse with gemtuzumab and cytarabine versus cytarabine.
- Author
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Prebet, Thomas, Etienne, Anne, Devillier, Raynier, Romeo, Emilie, Charbonnier, Aude, D'incan, Evelyne, Esterni, Benjamin, Arnoulet, Christine, Blaise, Didier, and Vey, Norbert
- Subjects
ACUTE myeloid leukemia ,CYTOGENETICS ,CYTARABINE ,DISEASE relapse ,DRUG efficacy - Abstract
BACKGROUND: Acute myeloid leukemia (AML) in first relapse is associated with a poor outcome even when treated with intermediate- to high-dose cytarabine (IHDAraC). Gemtuzumab ozogamycin (GO) used as a single agent has clinical activity in relapsed and refractory AML. Various combination regimens of GO have been developed, but few data are available regarding their efficacy compared with IHDAraC-based regimens. METHODS: The authors performed a retrospective analysis of response and survival in 90 AML patients in first relapse treated with either IHDAraC (n = 56) or IHDAraC + GO (n = 34). Patient characteristics of the two groups were comparable. RESULTS: Median follow-up was 37 months. Compared with IHDAraC, IHDAraC + GO induction was associated with a better response rate (68% vs 45%, P = .04), a better overall survival (median, 35 months vs 6 months, P = .001), and a better event-free survival (24 months vs 6 months, P = .002). This effect was limited to patients with low-risk and intermediate- risk cytogenetics. In multivariate analysis, age, cytogenetic risk, first complete remission duration, and the use of IHDAraC + GO were independently associated with better results. CONCLUSIONS: This study showed that the addition of GO to IHDAraC is associated with a better efficacy for patients in first relapse of AML with low- or intermediate- risk cytogenetics. Prospective controlled studies of GO in this population are warranted. Patients with high-risk cytogenetics should be offered investigational new drugs. Cancer 2011;117:974-81. [ABSTRACT FROM AUTHOR]
- Published
- 2011
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43. Oneversustwo high-dose cytarabine-based consolidation before autologous stem cell transplantation for young acute myeloblastic leukaemia patients in first complete remission.
- Author
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Jourdan, Eric, Rigal-Huguet, Françoise, Marit, Gerald, Vey, Norbert, Dastugue, Nicole, Fegueux, Nathalie, Molina, Lysiane, Gastaut, Jean-Albert, Legros, Laurence, Zerazhi, Hacene, Cailleres, Sylvie, Bauduer, Frédéric, Bordessoule, Dominique, Attal, Michel, Blaise, Didier, and Pigneux, Arnaud
- Subjects
STEM cells ,DRUG therapy ,ACUTE myeloid leukemia ,PATIENTS ,LEUKEMIA ,TRANSPLANTATION of organs, tissues, etc. - Abstract
We report on a randomized trial aimed to determine the impact of a second consolidative high-dose cytarabine-based chemotherapy (HiDAC) in patients with acute myeloid leukaemia prior to an autologous stem cell transplantation (ASCT). Patients aged 18–60 years, in complete remission (CR) received a first consolidation with daunorubicin and cytarabine at reduced dose. Patients not allocated to allogeneic transplantation received one course of HiDAC and then were randomized to receive an ASCT immediately (HiDAC 1 group) or after one more course of HiDAC (HiDAC 2 group). Out of the 437 initial patients, 351 achieved CR (80%), of those 277 (79%) were eligible for first HiDAC, and 128 (36%) were randomized (HiDAC 1: 65, HiDAC 2: 63). Overall survival, leukaemia-free survival and cumulative incidence of relapse and non-relapse deaths were 41% and 53% (P = 0·14), 39% and 48% (P = 0·12), 57% and 47% (P = 0·11), 8% and 8% (P = 0·95) for HiDAC 1 and HiDAC 2 groups, respectively. Further studies are warranted with a larger number of patients to test the place of a second course of HiDAC in this setting. [ABSTRACT FROM AUTHOR]
- Published
- 2005
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44. Leukemia relapse following unmanipulated haploidentical transplantation: a risk factor analysis on behalf of the ALWP of the EBMT.
- Author
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Piemontese, Simona, Boumendil, Ariane, Labopin, Myriam, Schmid, Christoph, Ciceri, Fabio, Arcese, William, Koc, Yener, Gulbas, Zafar, Tischer, Johanna, Bruno, Benedetto, Wu, Depei, Blaise, Didier, Beelen, Dietrich, Irrera, Giuseppe, Ruggeri, Annalisa, Houhou, Mohamed, Mohty, Mohamad, and Nagler, Arnon
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DISEASE risk factors ,FACTOR analysis ,ACUTE myeloid leukemia ,LEUKEMIA ,STEM cell transplantation - Abstract
Background: As information on incidence, risk factors, and outcome of acute leukemia (AL) relapse after unmanipulated haploidentical stem cell transplantation (haplo-SCT) is scarce, a retrospective registry study was performed by the Acute Leukemia Working Party of the European Society for Blood and Marrow Transplantation. Methods: Among 1652 transplants performed for lymphoblastic and myeloid AL between 2007 and 2014, 587 patients (acute lymphoblastic leukemia (ALL) 131, acute myeloid leukemia (AML) 456) with detailed information were analyzed aiming to identify risk factors for post-transplant relapse and for overall survival (OS) after relapse. Results: The cumulative incidence of relapse at 3 years was 44% (35–53%) for ALL and 32% (27–36%) for AML (p = 0.023). In ALL, risk factors for relapse were disease status different from the first complete remission (CR1) at haplo-SCT (CR2 vs CR1: HR 2.85, p = 0.011; advanced vs CR1: HR 14.28, p < 0.0001) and male donor gender (HR 3.64, p = 0.0002), while in AML, risk factors were advanced disease at haplo-SCT (advanced vs CR1: HR 3.95, p < 0.0001) and comorbidities (HCT-CI) ≥ 3 (HR 1.75, p = 0.014). Transplants performed in more recent years were associated with lower relapse incidence (RI) in AML, but not in ALL (HR 0.91, p = 0.042). After relapse, median follow-up was 13 months (mos). OS at 1-year post relapse was 18%. Prognostic factors for superior OS after relapse were remission at time of haplo-SCT (CR vs advanced: HR 0.71, p = 0.028), time from transplant to relapse (≥ 5 mos vs < 5 mos: HR 0.530, p < 0.0001), and bone marrow as a stem cell source (peripheral blood (PB) vs bone marrow (BM): HR 1.473, p = 0.016). Conclusions: Risk factors for relapse after haploidentical transplantation were disease specific. Longer OS after relapse was achieved in particular by patients both in CR at haplo-SCT and relapsing more than 5 months after transplant (1-year OS 33%). [ABSTRACT FROM AUTHOR]
- Published
- 2019
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45. NKp46 expression on NK cells as a prognostic and predictive biomarker for response to allo-SCT in patients with AML.
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Chretien, Anne-Sophie, Devillier, Raynier, Fauriat, Cyril, Orlanducci, Florence, Harbi, Samia, Le Roy, Aude, Rey, Jérôme, Bouvier Borg, Gaelle, Gautherot, Emmanuel, Hamel, Jean-François, Ifrah, Norbert, Lacombe, Catherine, Cornillet-Lefebvre, Pascale, Delaunay, Jacques, Toubert, Antoine, Arnoulet, Christine, Vey, Norbert, Blaise, Didier, and Olive, Daniel
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KILLER cells ,ACUTE myeloid leukemia ,STEM cell transplantation ,PATIENTS - Abstract
NKp46 is a major determinant of natural killer (NK) cell function and it is implicated in tumor immune surveillance in acute myeloid leukemia (AML). The purpose of this study was to investigate the prognostic significance of NKp46 expression in an independent cohort of patients with AML, and to investigate the impact of NKp46 on clinical outcome after allogeneic stem cell transplantation (allo-SCT). NKp46 expression was assessed at diagnosis on NK cells by flow cytometry (N = 180 patients). Clinical outcome was evaluated with regard to NKp46 expression. Patients with NKp46highphenotype at diagnosis had better progression-free survival (PFS) and overall survival (OS) than patients with NKp46lowphenotype (74.3% vs. 46.6%,p= 0.014; 82.6% vs. 57.1%,p= 0.010, respectively). In multivariate analysis, high NKp46 was an independent factor for improved OS (HR = 0.409,p= 0.010) and PFS (HR = 0.335,p= 0.011). Subgroup analysis revealed that allo-SCT had a favorable impact on PFS in patients with NKp46highphenotype (p= 0.025). By contrast, allo-SCT did not impact PFS in patients with low NKp46 expression (p= 0.303). In conclusion, we validate the prognostic value of NKp46 expression at diagnosis in AML. However, the prognostic value of NKp46 expression is limited to patients treated with allo-SCT, thus suggesting that NKp46 status may be predictive for allo-SCT responsiveness. [ABSTRACT FROM PUBLISHER]
- Published
- 2017
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46. Autologous stem cell transplantation for adult acute myelocytic leukemia in first remission-Better outcomes after busulfan and melphalan compared with busulfan and cyclophosphamide: A retrospective study from the Acute Leukemia Working Party of the European Society for Blood and Marrow Transplantation (EBMT).
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Gorin, Norbert-Claude, Labopin, Myriam, Czerw, Tomasz, Pabst, Thomas, Blaise, Didier, Dumas, Pierre-Yves, Nemet, Damir, Arcese, William, Trisolini, Silvia Maria, Wu, Depei, Huynh, Anne, Zuckerman, Tsila, Meijer, Ellen, Cagirgan, Seckin, Cornelissen, Jan, Houhou, Mohamed, Polge, Emmanuelle, Mohty, Mohamad, and Nagler, Arnon
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ANTINEOPLASTIC agents ,STEM cell transplantation ,CYCLOPHOSPHAMIDE ,MELPHALAN ,BUSULFAN ,AUTOGRAFTS ,COMBINED modality therapy ,IMMUNOSUPPRESSION ,ACUTE myeloid leukemia ,DISEASE remission ,RETROSPECTIVE studies ,THERAPEUTICS - Abstract
Background: Autologous stem cell transplantation (ASCT) for adult acute myelogenous leukemia (AML) is a valid therapeutic option for patients with good-risk and intermediate-risk disease. The authors used the registry of the European Society for Blood and Marrow Transplantation to compare combined busulfan and melphalan (BUMEL) with combined busulfan and cyclophosphamide (BUCY) before transplantation.Methods: From 2005 to 2013, 853 patients with available cytogenetics underwent ASCT in first remission, including 257 after receiving BUMEL and 596 after receiving BUCY. The proportion of patients with good-risk AML was lower in those who received BUMEL (14% vs 20%; P = .02). More patients who received BUMEL underwent autograft in molecular remission (89% vs 78%; P = .02). Three years after transplantation, the relapse incidence (RI) was 48.7%, the leukemia-free survival (LFS) rate was 47.7%, the overall survival (OS) rate was 66.2%, and the nonrelapse mortality (NRM) rate was 3.6%.Results: Patients who underwent an autograft after receiving BUMEL fared better than those who underwent an autograft after receiving BUCY with a lower RI (39.5% vs 52.2%; hazard ratio [HR], 0.65; 95% confidence interval [CI], 0.49-0.87; P = .003) a better LFS (55.4% vs 44.6%; HR, 0.69; 95% CI, 0.53-0.89; P = .005), and a better OS (73.8% vs 63%; HR, 0.62; 95% CI, 0.47-0.82; P = .0007). There was no difference in the NRM rate (BUMEL vs BUCY, 4.5% vs 3.2%, respectively). Among 74 patients in the BUMEL group and 187 in the BUCY group who underwent autograft in molecular remission, the RI was 30% versus 51%, respectively (univariate analysis; P = .01), and the LFS rate was 66% versus 47%, respectively (univariate analysis; P = .03).Conclusions: In patients with AML in first complete remission who undergo ASCT, the BUMEL combination is a better preparative regimen. Cancer 2017;123:824-31. © 2016 American Cancer Society. [ABSTRACT FROM AUTHOR]- Published
- 2016
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47. Effect of Graft Source on Unrelated Donor Hemopoietic Stem Cell Transplantation in Adults with Acute Myeloid Leukemia after Reduced-Intensity or Nonmyeloablative Conditioning: A Study from the Société Francaise de Greffe de Moelle et de Thérapie Cellulaire
- Author
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Malard, Florent, Milpied, Noel, Blaise, Didier, Chevallier, Patrice, Michallet, Mauricette, Lioure, Bruno, Clément, Laurence, Hicheri, Yosr, Cordonnier, Catherine, Huynh, Anne, Yakoub-Agha, Ibrahim, Peffault de Latour, Regis, and Mohty, Mohamad
- Subjects
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HEMATOPOIETIC system , *ACUTE myeloid leukemia , *MYELOID leukemia , *BONE marrow diseases , *NONLYMPHOID leukemia - Abstract
This retrospective report compared the 4-year outcomes of allogeneic stem cell transplantation (allo-SCT) in 651 adult patients with acute myeloid leukemia receiving a reduced-intensity (RIC) or nonmyeloablative conditioning (NMA) regimen according to the type of unrelated donors. These were either umbilical cord blood (UCB, n = 205), a 9/10 mismatched unrelated donor (MisMUD, n = 99), or a 10/10 matched unrelated donor (MUD, n = 347) graft. Neutrophil recovery was slower in UCB (74.5% by day 42) compared with MisMUD (94.8%) and MUD (95.6%) ( P < .001). There was no significant difference in nonrelapse mortality between UCB and both MUD (hazard ratio [HR], 1.05; 95% confidence interval [CI], .62 to 1.78; P = .85) and MisMUD (HR, 1.58; 95% CI, .88 to 2.83; P = .13) The relapse/progression was similar between UCB and MisMUD (HR, .62; 95% CI, .37 to 1.03; P = .07), but was significantly lower in MUD compared with UCB (HR, .60; 95% CI, .39 to .92; P = .02). The rate of extensive chronic graft-versus-host disease (GVHD) was similar between UCB and both MUD (HR, 2.15; 95% CI, .93 to 4.97; P = .08) and MisMUD (HR, 1.84; 95% CI, .68 to 4.95; P = .23). The rate of severe grade III and IV acute GVHD was significantly increased in MisMUD compared with UCB (HR, 2.61; 95% CI, 1.30 to 5.23; P = .007). There was no significant difference in overall survival between UCB and both MisMUD (HR, .98; 95% CI, .66 to 1.45; P = .92) and MUD (HR, .74; 95% CI, .52 to 1.03; P = .08). These data suggest that in the setting of RIC/NMA, allo-SCT UCB is a valid alternative graft source, with significantly less chronic GVHD, compared with MisMUD, when there is no MUD available or when urgent transplantation is needed. [ABSTRACT FROM AUTHOR]
- Published
- 2015
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48. Calcineurin Inhibitor Alone or in Combination with Mycophenolate Mofetil for Graft-Versus-Host-Disease Prophylaxis in Patients with Acute Myeloid Leukemia Undergoing Transplantation from Matched Unrelated Donors: A Study from the ALWP of the EBMT.
- Author
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Paviglianiti, Annalisa, Labopin, Myriam, Blaise, Didier, Socié, Gérard, Bulabois, Claude-Eric, Lioure, Bruno, Fegueux, Nathalie, Gerbitz, Arnim, Guillermin, Gaelle, Maertens, Johan, Chevallier, Patrice, Huynh, Anne, Turlure, Pascal, Deconinck, Eric, Forcade, Edouard, Nagler, Arnon, and Mohty, Mohamad
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- *
ACUTE myeloid leukemia , *MYCOPHENOLIC acid , *CALCINEURIN , *PREVENTIVE medicine , *TRANSPLANTATION of organs, tissues, etc. - Abstract
Cyclosporine A (CsA) alone or in combination with mycophenolate mofetil (MMF) has been used as graft-versus-host-disease (GvHD) prophylaxis since the development of reduced intensity conditioning (RIC). The association of CsA+MMF, while commonly used after transplantation from a matched unrelated donor (MUD), has never been tested in a large randomized prospective trial. We retrospectively investigated the outcomes of 497 adult patients with AML in complete remission (CR) undergoing a MUD transplant between 2007-2017 using CsA+MMF or CsA alone as GvHD prophylaxis, and registered with the ALWP of the EBMT. Patients had CsA alone (n=183) or CsA+MMF (n=314) as GvHD prophylaxis. All underwent a RIC regimen with fludarabine and busulfan and received anti-thymocyte globulin. The median age at transplant was similar (59 and 60 years in the CsA and CsA+MMF group). The median follow-up was not significantly different between the two groups (33 vs 34 months in CsA and CsA+MMF, respectively). Disease status at transplant was first complete remission (CR1) for 81% in CsA group and 86% in CsA+MMF group (p=NS). Peripheral blood stem cells (PBSC) was the graft source in 93% of patients receiving CsA alone and in 96% of patients who received CsA+MMF (p=0.17). All but 2 patients engrafted. The 100 day cumulative incidence (CI) of grade II-IV and grade III-IV acute GvHD were 30% and 10%, respectively. The 2-year CI of chronic GvHD was 35% and CI of extensive cGvHD was 15%. The 2-year CI of non-relapse mortality (NRM) and relapse were 19% and 25%, respectively. Disease recurrence (n=31), GvHD (n=20) and infection (n=17) were the most common causes of death in the CsA group. Relapse (n=53), GvHD (n=28) and infection (n=28) were the most frequent causes of death in the CsA+MMF group. The 2-year GVHD-free relapse-free survival (GRFS), leukemia- free survival (LFS), and overall survival (OS) were 45%, 56% and 60%, respectively. On multivariate analysis (MVA), no statistically significant differences between the two groups with respect to relapse, NRM, LFS, OS, acute and chronic GvHD were identified. A positive cytomegalovirus serology of the donor was associated with higher NRM [HR=2.03, p<0.001] and higher cGvHD [HR=1.44, p=0.03] and a lower OS [HR 1.66, p<0.001], LFS [HR=1.69, p=0.001] and GRFS [HR=1.75, p<0.001]. In a subgroup analysis in patients in CR1 who received PBSC, no differences were detected between the two groups for relapse, NRM, LFS, OS, or aGvHD. Patients who received CsA alone tended to have a higher cGvHD (p=0.05). However, this finding was not statistically significant in MVA. We observed comparable outcomes in AML patients in CR1 who underwent MUD transplantation and RIC with CsA+MMF or CsA alone as GvHD prophylaxis. This suggests that both strategies may be considered valid approaches. Randomized trials are needed to further assess which patients could benefit from the addition of MMF in GvHD prophylaxis [ABSTRACT FROM AUTHOR]
- Published
- 2020
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49. Reduced-Intensity versus Myeloablative Conditioning in Cord Blood Transplantation for Acute Myeloid Leukemia (40-60 years) across Highly Mismatched HLA Barriers—On Behalf of Eurocord and the Cellular Therapy & Immunobiology Working Party (CTIWP) of EBMT
- Author
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Sheth, Vipul, Volt, Fernanda, Sanz, Jaime, Clement, Laurence, Cornelissen, Jan, Blaise, Didier, Sierra, Jorge, Michallet, Mauricette, Saccardi, Riccardo, Rocha, Vanderson, Gluckman, Eliane, Chabannon, Christian, and Ruggeri, Annalisa
- Subjects
- *
CORD blood transplantation , *ACUTE myeloid leukemia , *CELLULAR therapy , *CORD blood , *ALEMTUZUMAB , *IMMUNOLOGY , *GRAFT versus host disease - Abstract
• In HLA mismatched umbilical cord blood transplantation (UCBT), reduced-intensity conditioning provided comparable results to myeloablative conditioning for patients with acute myeloid leukemia (AML) aged 40 to 60 years. • The main factor associated with poor outcomes after HLA mismatched UCBT was advanced disease status. • UCBT remains an alternative graft source for patients 40 to 60 years old with AML. The use of myeloablative conditioning (MAC) in umbilical cord blood transplantation (UCBT) has been associated with high nonrelapse mortality (NRM) in patients aged >40 years, especially those having a high HLA disparity, thus limiting wider applications. We hypothesized that the NRM advantage of reduced-intensity conditioning (RIC) and higher graft-versus-leukemia effect associated with greater HLA disparities would expand its use for patients (aged 40 to 60 years) without compromising efficacy and compared outcomes between RIC and MAC regimens. In total, 288 patients aged 40 to 60 years, with de novo acute myeloid leukemia, receiving UCBT with at least 2 HLA mismatches with RIC (n = 166) or MAC (n = 122) regimens were included. As compared to RIC, the MAC cohort included relatively younger patients, having received more single UCBT, with lower total nucleated cell counts and more in vivo T cell depletion. Median time to neutrophil engraftment, infections (bacterial, viral, and fungal), and grade II to IV acute and chronic graft-versus-host disease were similar in both groups. In the multivariate analysis, overall survival (hazard ratio [HR], 0.98; P =.9), NRM (HR, 0.68; P =.2), and relapse (HR, 1.24; P =.5) were not different between RIC and MAC. Refractory disease was associated with worse survival. Outcomes of UBCT for patients aged 40 to 60 years having ≥2 HLA mismatches are comparable after the RIC or MAC regimen. [ABSTRACT FROM AUTHOR]
- Published
- 2020
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50. Comparable Long-Term Outcome after Allogeneic Stem Cell Transplantation from Sibling and Matched Unrelated Donors in Patients with Acute Myeloid Leukemia Older Than 50 Years: A Report on Behalf of the Acute Leukemia Working Party of the European Society for Blood and Marrow Transplantation
- Author
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Shimoni, Avichai, Labopin, Myriam, Savani, Bipin, Byrne, Michael, Volin, Liisa, Finke, Jürgen, Niederwieser, Dietger, Ehninger, Gerhard, Blaise, Didier, Beelen, Dietrich, Tabrizi, Reza, Sengeloev, Henrik, Ganser, Arnold, Cornelissen, Jan J., Mohty, Mohamad, and Nagler, Arnon
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- *
STEM cell transplantation , *ACUTE myeloid leukemia , *ACUTE leukemia , *SIBLINGS , *BONE marrow , *ALEMTUZUMAB - Abstract
• Marked improvement has been achieved in recent years in stem cell transplantation (SCT) from unrelated donors. • Long-term outcome is equivalent after SCT from unrelated and sibling donors. • Patients who are leukemia-free 2 years after SCT can expect a favorable outcome. Allogeneic stem cell transplantation (SCT) is potentially curative therapy in acute myeloid leukemia (AML). Marked improvement has been achieved with SCT from matched unrelated donors (MUDs) in recent years. However, there are limited data comparing the long-term outcomes (beyond 10 years) after SCT from sibling donors and MUDs in older patients with AML. We analyzed these outcomes in a large cohort of patients with AML (n = 1134), age ≥50 years, who were alive and leukemia-free 2 years after SCT from matched siblings (n = 848) or MUDs (n = 286), with a median follow-up of 8.9 years. The median age was 56 and 58 years after SCT from siblings and MUDs, respectively (P =.005). In the sibling group, 77%, 12%, and 11% were in first complete remission (CR1), second complete remission (CR2), and active leukemia at SCT compared with 50%, 25%, and 25% in the MUD group, respectively (P <.001). Sixty-one percent of siblings and 62% of MUDs had reduced-intensity conditioning (P =.78). The 10-year leukemia-free survival (LFS) of patients surviving leukemia-free 2 years after SCT was 72% and 62%, respectively (P =.30). Multivariate analysis identified active leukemia at SCT (hazard ratio [HR], 1.86; P =.0001) or CR2 (HR, 1.51; P =.02) compared with CR1, female recipients (HR, 0.71; P =.006), adverse cytogenetics (HR, 2.52; P =.01), and prior graft-versus-host disease (HR, 1.31; P =.04) as independent factors predicting LFS. Donor and conditioning type were not significant. The cumulative incidence was 15% and 17% (P =.97) for late relapse mortality and 13% and 21% for late nonrelapse mortality, respectively (P =.15). In conclusion, long-term LFS is similar, and patients who are leukemia-free 2 years after SCT can expect favorable outcomes with both donor types. [ABSTRACT FROM AUTHOR]
- Published
- 2019
- Full Text
- View/download PDF
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