Browsing by Subject "1ST COMPLETE REMISSION"

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  • Saraceni, Francesco; Labopin, Myriam; Forcade, Edouard; Kroeger, Nicolaus; Socie, Gerard; Niittyvuopio, Riitta; Cornelissen, Jan J.; Labussiere-Wallet, Helene; Blaise, Didier; Choi, Goda; Byrne, Jenny L.; Guillerm, Gaelle; Marchand, Tony; Esteve, Jordi; Bazarbachi, Ali; Savani, Bipin; Olivieri, Attilio; Nagler, Arnon; Mohty, Mohamad (2021)
    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
  • Poire, Xavier; Labopin, Myriam; Polge, Emmanuelle; Passweg, Jakob; Craddock, Charles; Blaise, Didier; Cornelissen, Jan J.; Volin, Liisa; Russell, Nigel H.; Socie, Gerard; Michallet, Mauricette; Fegueux, Nathalie; Chevallier, Patrice; Brecht, Arne; Hunault-Berger, Mathilde; Mohty, Mohamad; Esteve, Jordi; Nagler, Arnon (2018)
    Intermediate-risk cytogenetic acute myeloid leukemia with an internal tandem duplication of FLT3 (FLT3-ITD) is associated with a high risk of relapse, and is now a standard indication for allogeneic stem cell transplantation. Nevertheless, most studies supporting this strategy have been performed in young patients. To address the benefit of allogeneic transplantation in the elderly, we made a selection from the European Society for Blood and Marrow Transplantation registry of de novo intermediate-risk cytogenetic acute myeloid leukemia harboring FLT3-ITD in patients aged 60 or over and transplanted from a related or unrelated donor between January 2000 and December 2015. Two hundred and ninety-one patients were identified. Most patients received a reduced-intensity conditioning (82%), while donors consisted of an unrelated donor in 161 (55%) patients. Two hundred and twelve patients received their transplantation in first remission, 37 in second remission and 42 in a more advanced stage of the disease. The 2-year leukemia-free survival rate was 56% in patients in first remission, 22% in those in second remission and 10% in patients with active disease, respectively (P= 60 with FLT3-ITD acute myeloid leukemia in first remission, similarly to current treatment recommendations for younger patients.
  • Poire, Xavier; Labopin, Myriam; Polge, Emmanuelle; Forcade, Edouard; Ganser, Arnold; Volin, Liisa; Michallet, Mauricette; Blaise, Didier; Yakoub-Agha, Ibrahim; Maertens, Johan; Richard Espiga, Carlos; Cornelissen, Jan; Finke, Jurgen; Mohty, Mohamad; Esteve, Jordi; Nagler, Arnon (2020)
    Deletion 5q or monosomy 5 (-5/5q-) in acute myeloid leukemia (AML) is a common high-risk feature that is referred to allogeneic stem cell transplantation. However, -5/5q- is frequently associated with other high-risk cytogenetic aberrations such as complex karyotype, monosomal karyotype, monosomy 7 (-7), or 17p abnormalities (abn (17p)), the significance of which is unknown. In order to address this question, we studied adult patients with AML harboring -5/5q- having their first allogeneic transplantation between 2000 and 2015. Five hundred and one patients with -5/5q- have been analyzed. Three hundred and thirty-eight patients (67%) were in first remission and 142 (28%) had an active disease at time of allogeneic transplantation. The 2-year probabilities of overall survival and leukemia-free survival were 27% and 20%, respectively. The 2-year probability of treatment-related mortality was 20%. We identified four different cytogenetic groups according to additional abnormalities with prognostic impact: -5/5q- without complex karyotype, monosomal karyotype or abn(17p), -5/5q- within a complex karyotype, -5/5q- within a monosomal karyotype and the combination of -5/5q- with abn(17p). In multivariate analysis, factors associated with worse overall survival and leukemia-free survival across the four groups were active disease, age, monosomal karyotype, and abn(17p). The presence of -5/5q- without monosomal karyotype or abn(17p) was associated with a significantly better survival rate while -5/5q- in conjunction with monosomal karyotype or abn(17p) translated into a worse outcome. The patients harboring the combination of -5/5q- with abn(17p) showed very limited benefit from allogeneic transplantation.
  • European Soc Blood Marrow Transpla; HOVON-SAKK (2018)
    Background. Disease recurrence remains the major cause of death in adults with acute myeloid leukaemia (AML) treated using either intensive chemotherapy (IC) or allogenic stem cell transplantation (allo-SCT). Aims. The timely delivery of maintenance drug or cellular therapies represent emerging strategies with the potential to reduce relapse after both treatment modalities, but whilst the determinants of overall relapse risk have been extensively characterized the factors determining the timing of disease recurrence have not been characterized. Materials and Methods. We have therefore examined, using a series of sequential landmark analyses, relapse kinetics in a cohort of 2028 patients who received an allo-SCT for AML in CR1 and separately 570 patients treated with IC alone. Results. In the first 3 months after allo-SCT, the factors associated with an increased risk of relapse included the presence of the FLT3-ITD (P <0.001), patient age (P = 0.012), time interval from CR1 to transplant (P <0.001) and donor type (P = 0.03). Relapse from 3 to 6 months was associated with a higher white cell count at diagnosis (P = 0.001), adverse-risk cytogenetics (P <0.001), presence of FLT3-ITD mutation (P <0.001) and time interval to achieve first complete remission (P = 0.013). Later relapse was associated with adverse cytogenetics, mutated NPM1, absence of chronic graft-versus-host disease (GVHD) and the use of in vivo T-cell depletion. In patients treated with IC alone, the factors associated with relapse in the first 3 months were adverse-risk cytogenetics (P <0.001) and FLT3-ITD status (P = 0.001). The factors predicting later relapse were the time interval from diagnosis to CR1 (P = 0.22) and time interval from CR1 to IC (P = 0.012). Discussion and Conclusion. Taken together, these data provide novel insights into the biology of disease recurrence after both allo-SCT and IC and have the potential to inform the design of novel maintenance strategies in both clinical settings.
  • Giebel, Sebastian; Labopin, Myriam; Czerw, Tomasz; Socie, Gerard; Blaise, Didier; Ghavamzadeh, Ardeshir; Passweg, Jacob; Ljungman, Per; Poire, Xavier; Chevallier, Patrice; Remenyi, Peter; Rambaldi, Alessandro; Anafasyev, Boris; Fegueux, Nathalie; Rovira, Montserrat; Itälä-Remes, Maija; Bornhaeuser, Martin; Mohty, Mohamad; Nagler, Arnon (2019)
    Background: Anti-thymocyte globulin (ATG) is widely used to prevent graft-versus-host disease (GVHD) after allogeneic peripheral blood stem cell transplantation (alloPBSCT). The goal of this study was to retrospectively assess the effect of ATG on outcomes in the setting of Philadelphia chromosome-positive acute lymphoblastic leukaemia (Ph+ ALL). Methods: In the analysis, 1170 adult patients undergoing alloPBSCT from human leucocyte antigen-matched sibling or unrelated donors in the first complete remission between 2007 and 2016 were included. ATG was used in 429/575 (75%) and 121/595 (20%) patients transplanted from unrelated or sibling donors, respectively. Results: The incidence of chronic GVHD was 35% for patients treated with ATG compared with 52% in those not receiving ATG (p <0.001), while the rate of extensive chronic GVHD was 16% and 36%, respectively (p <0.001). The probability of survival free from GVHD and relapse (GRFS) was 42% and 32%, respectively (p = 0.002). In a multivariate model, the use of ATG was associated with reduced risk of overall chronic GVHD (hazard ratio [HR] = 0.52, p <0.001) and extensive chronic GVHD (HR = 0.46, p <0.001). It was also associated with better GRFS (HR = 0.77, p = 0.007), despite increased risk of relapse (HR = 1.41, p = 0.02). No significant effect was found with regard to the risk of non-relapse mortality and overall mortality. Conclusions: The use of ATG for patients with Ph+ ALL undergoing alloPBSCT is associated with reduced risk of chronic GVHD without impact on survival and therefore, could be considered. However, increased risk of relapse suggests the need for strict monitoring of minimal residual diseases and appropriate interventions after transplantation. (C) 2018 Elsevier Ltd. All rights reserved.
  • Canaani, Jonathan; Beohou, Eric; Labopin, Myriam; Socie, Gerard; Huynh, Anne; Volin, Liisa; Cornelissen, Jan; Milpied, Noel; Gedde-Dahl, Tobias; Deconinck, Eric; Fegueux, Nathalie; Blaise, Didier; Mohty, Mohamad; Nagler, Arnon (2017)
    The French, American, and British (FAB) classification system for acute myeloid leukemia (AML) is extensively used and is incorporated into the AML, not otherwise specified (NOS) category in the 2016 WHO edition of myeloid neoplasm classification. While recent data proposes that FAB classification does not provide additional prognostic information for patients for whom NPM1 status is available, it is unknown whether FAB still retains a current prognostic role in predicting outcome of AML patients undergoing allogeneic stem cell transplantation. Using the European Society of Blood and Bone Marrow Transplantation registry we analyzed outcome of 1690 patients transplanted in CR1 to determine if FAB classification provides additional prognostic value. Multivariate analysis revealed that M6/M7 patients had decreased leukemia free survival (hazard ratio (HR) of 1.41, 95% confidence interval (CI), 1.01-1.99; P = .046) in addition to increased nonrelapse mortality (NRM) rates (HR, 1.79; 95% CI, 1.06-3.01; P = .028) compared with other FAB types. In the NPM1(wt) AML, NOS cohort, FAB M6/M7 was also associated with increased NRM (HR, 2.17; 95% CI, 1.14-4.16; P = .019). Finally, in FLT3-ITD+ patients, multivariate analyses revealed that specific FAB types were tightly associated with adverse outcome. In conclusion, FAB classification may predict outcome following transplantation in AML, NOS patients.
  • Toft, N.; Birgens, H.; Abrahamsson, J.; Griskevicius, L.; Hallbook, H.; Heyman, M.; Klausen, T. W.; Jonsson, O. G.; Palk, K.; Pruunsild, K.; Quist-Paulsen, P.; Vaitkeviciene, G.; Vettenranta, K.; Asberg, A.; Frandsen, T. L.; Marquart, H. V.; Madsen, H. O.; Noren-Nystrom, U.; Schmiegelow, K. (2018)
    Adults with acute lymphoblastic leukemia (ALL) do worse than children. From 7/2008 to 12/2014, Nordic and Baltic centers treated 1509 consecutive patients aged 1-45 years with Philadelphia chromosome-negative ALL according to the NOPHO ALL2008 without cranial irradiation. Overall, 1022 patients were of age 1-9 years (A), 266 were 10-17 years (B) and 221 were 18-45 years (C). Sixteen patients (three adults) died during induction. All others achieved remission after induction or 1-3 intensive blocks. Subsequently, 45 patients (12 adults) died, 122 patients relapsed (32 adults) with a median time to relapse of 1.6 years and 13 (no adult) developed a second malignancy. Median follow-up time was 4.6 years. Among the three age groups, older patients more often had higher risk ALL due to T-ALL (32%/25%/9%, P
  • Poire, Xavier; Labopin, Myriam; Polge, Emmanuelle; Volin, Liisa; Finke, Juergen; Ganser, Arnold; Blaise, Didier; Yakoub-Agha, Ibrahim; Beelen, Dietrich; Forcade, Edouard; Lioure, Bruno; Socie, Gerard; Niederwieser, Dietger; Labussiere-Wallet, Helene; Maertens, Johan; Cornelissen, Jan; Craddock, Charles; Mohty, Mohamad; Esteve, Jordi; Nagler, Arnon (2020)
    Monosomy 7 or deletion 7q (-7/7q-) is the most frequent adverse cytogenetic features reported in acute myeloid leukemia (AML), and is a common indication for allogeneic stem cell transplantation (SCT). Nevertheless, -7/7q- occurs frequently with other high-risk cytogenetic abnormalities such as complex karyotype (CK), monosomal karyotype (MK), monosomy 5 or deletion 5q (-5/5q-), 17p abnormalities (abn(17p)) or inversion of chromosome 3 (inv(3)), the presence of which may influence the outcomes after SCT. A total of 1109 patients were allocated to this study. Two-year probability of leukemia-free survival (LFS) and overall survival (OS) were 30% and 36%, respectively. Two-year probability of non-relapse mortality (NRM) was 20%. We defined five different cytogenetic subgroups: the "-7/7q- +/- CK group- designated group1," the "MK group-designated group 2," the "-5/5q- group- designated group 3," the "abn(17p) group- designated group 4" and the "inv(3) group- designated group 5." The 2-year probability of LFS in first remission was 48% for group 1, 36.4% for group 2, 28.4% for group 3, 19.1% for group 4 and 17.3% for group 5, respectively (P <.001). Multivariate analysis confirmed those significant differences across groups. Note, SCT in -7/7q- AML provides durable responses in one third of the patients. The presence of -7/7q- with or without CK in the absence of MK, abn(17p) or inv (3) is associated with a better survival after SCT. On the contrary, addition of MK, -5/5q-, abn(17p) or inv(3) identifies a sub-group of patients with poor prognosis even after SCT.
  • Brissot, Eolia; Labopin, Myriam; Beckers, Marielle M.; Socie, Gerard; Rambaldi, Alessandro; Volin, Liisa; Finke, Juergen; Lenhoff, Stig; Kroeger, Nicolaus; Ossenkoppele, Gert J.; Craddock, Charles F.; Yakoub-Agha, Ibrahim; Gurman, Gunhan; Russell, Nigel H.; Aljurf, Mahmoud; Potter, Michael N.; Nagler, Armon; Ottmann, Oliver; Cornelissen, Jan J.; Esteve, Jordi; Mohty, Mohamad (2015)
    This study aimed to determine the impact of tyrosine kinase inhibitors given pre- and post- allogeneic stem cell transplantation on long- term outcome of patients allografted for Philadelphia chromosome- positive acute lymphoblastic leukemia. This retrospective analysis from the EBMT Acute Leukemia Working Party included 473 de novo Philadelphia chromosome- positive acute lymphoblastic leukemia patients in first complete remission who underwent an allogeneic stem cell transplantation using a human leukocyte antigen- identical sibling or human leukocyte antigen- matched unrelated donor between 2000 and 2010. Three hundred and ninety patients received tyrosine kinase inhibitors before transplant, 329 at induction and 274 at consolidation. Kaplan- Meier estimates of leukemia- free survival, overall survival, cumulative incidences of relapse incidence, and non- relapse mortality at five years were 38%, 46%, 36% and 26%, respectively. In multivariate analysis, tyrosine- kinase inhibitors given before allogeneic stem cell transplantation was associated with a better overall survival ( HR= 0.68; P= 0.04) and was associated with lower relapse incidence ( HR= 0.5; P= 0.01). In the post- transplant period, multivariate analysis identified prophylactic tyrosine- kinase inhibitor administration to be a significant factor for improved leukemiafree survival ( HR= 0.44; P= 0.002) and overall survival ( HR= 0.42; P= 0.004), and a lower relapse incidence ( HR= 0.40; P= 0.01). Over the past decade, administration of tyrosine kinase inhibitors before allogeneic stem cell transplantation has significantly improved the long- term allogeneic stem cell transplantation outcome of adult Philadelphia chromosome- positive acute lymphoblastic leukemia. Prospective studies will be of great interest to further confirm the potential benefit of the prophylactic use of tyrosine kinase inhibitors in the post- transplant setting.