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Cord blood transplantation for AML: Comparable LFS in patients with de novo versus secondary AML in CR1, an ALWP/EBMT study
Baron, F., Nagler, A., Galimard, J. E., Sanz, J., Versluis, J., Forcade, E., Chevallier, P., Sirvent, A., Anthias, C., Kuball, J., et al
British journal of haematology. 2023
Abstract
We investigated whether secondary versus de novo acute myeloid leukaemia (AML) would be associated with poor outcomes in adult acute AML patients in first complete remission (CR1) receiving unrelated cord blood transplantation (CBT). This is a retrospective study from the acute leukaemia working party of the European Society for Blood and Marrow Transplantation. Inclusion criteria included adult at first allogeneic haematopoietic cell transplantation between 2000 and 2021, unrelated single or double unit CBT, AML in CR1, no ex vivo T-cell depletion and no post-transplant cyclophosphamide. The primary end-point of the study was leukaemia-free survival (LFS). A total of 879 patients with de novo (n = 696) or secondary (n = 183) AML met the inclusion criteria. In multivariable analyses, sAML patients had non-significantly different LFS (HR = 0.98, p = 0.86), overall survival (HR = 1.07, p = 0.58), relapse incidence (HR = 0.74, p = 0.09) and non-relapse mortality (HR = 1.26, p = 0.13) than those with de novo AML. Our results demonstrate non-significantly different LFS following CBT in adult patients with secondary versus de novo AML.
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Impact of detectable measurable residual disease on umbilical cord blood transplantation
Baron, F., Labopin, M., Ruggeri, A., Sierra, J., Robinson, S., Labussiere-Wallet, H., Potter, M., Ribera, J. M., Deconinck, E., Rambaldi, A., et al
American journal of hematology. 2020
Abstract
The impact of measurable residual disease (MRD) on cord blood transplantation (CBT) outcomes has remained debated. To address this issue, we assessed the impact of measurable MRD at CBT on outcomes in large cohort of patients with acute leukemia. Inclusion criteria included adult patients with acute myeloid (AML) or acute lymphoblastic leukemia (ALL), CBT as first allo-HCT in first or second complete remission (CR) at transplantation, and known MRD status at the time of CBT. Data from 506 patients were included in the analysis. Among them, 317 patients had AML and 189 had ALL. Positive MRD was reported in 169 (33%) patients while the remaining 337 patients were MRD negative at CBT. At 2 years, relapse incidence was 18% in patients with MRD negativity versus 33% in those with MRD positivity at transplantation (P<0.001). Two-year leukemia-free survival (LFS) and overall survival (OS) were 57% and 60%, respectively, in MRD negative patients, versus 38% (P<0.001) and 48% (P=0.004), respectively, in those with MRD positivity. There was no interaction between the impact of MRD on OS and LFS and diagnosis (i.e. ALL versus AML), single or double CBT, and reduced-intensity or myeloablative conditioning. On multivariate analysis, MRD positivity was associated with a higher risk of relapse (HR=1.8, P=0.003), comparable non-relapse mortality (P=0.44), worse LFS (HR=1.4, P=0.008) and a trend towards worse OS (HR=1.3, P=0.065). In conclusion, these data suggest that novel strategies that are aiming to achieve MRD negativity at CBT are needed for leukemic patients with positive MRD pre-CBT. This article is protected by copyright. All rights reserved.
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Influence of donor and recipient gender on telomere maintenance following umbilical cord blood cell transplantation: A study by gitmo (gruppo italiano trapianto di midollo osseo)
Derenzini, E., Risso, A., Ruella, M., Spatola, T., Milone, G., Pioltelli, P., Iori, A. P., Santarone, S., Bosi, A., Rambaldi, A., et al
Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation. 2019
Abstract
Physiological loss of telomerase activity in adult life determines progressive telomere length (TL) shortening. Inflammation and oxidative damage are established causes of TL loss; moreover, males have shorter telomeres compared to females. Despite these notions, mechanisms regulating TL maintenance are poorly defined. As umbilical cord blood (UCB) cells harbor very long telomeres, not yet exposed to environmental damages, UCB transplantation (UCB-T) provides a unique experimental setting to study determinants of TL in humans. TL dynamics was analyzed on peripheral blood mononucleated cells (MNCs) from 36 patients (median age: 42 yrs.) undergoing UCB-T. TL was studied at a median of 20 months since UCB-T. A significantly longer TL (mean 8,698 bp, range 6521-11960) was documented in UCB-T recipients compared to age-matched healthy controls (mean 7,396 bp, range 4,375-11,108) (p<0.01). Among variables potentially influencing TL maintenance, including recipient features, graft type, transplant procedure, and engraftment kinetics, only donor/recipient gender combination was associated to TL, with longest TL in females receiving a male UCB (mean 10,063 bp, range 8,381-11,960). To further investigate this trend, telomerase activation was assessed in vitro. Experiments showed that telomerase subunits were preferentially up-regulated in male-derived bone marrow MNCs exposed ex-vivo to estradiol as compared to female MNCs. This implies an increased sensitivity of male-derived MNCs to telomerase activation induced by estradiol. The results suggest that extrinsic and modifiable factors such as hormonal status and female milieu could be major determinants of TL in humans providing the rationale for investigating hormonal-based approaches to counteract telomere erosion and aging-related diseases.
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Cord blood transplantation is associated with good outcomes in secondary Acute Myeloid Leukemia in first remission
Baron, F., Labopin, M., Ruggeri, A., Volt, F., Mohty, M., Blaise, D., Chevallier, P., Sanz, J., Fegueux, N., Cornelissen, J. J., et al
Journal of internal medicine. 2018
Abstract
BACKGROUND We conducted a retrospective survey within the European Society for Blood and Marrow Transplantation (EBMT) registry to assess the outcomes of cord blood transplantation (CBT) in secondary acute myeloid leukemia (sAML). METHODS Inclusion criteria consisted of ≥ 18 years of age, sAML, first CBT between 2002 and 2016, and either first complete remission (CR) or active disease at CBT. RESULTS One hundred forty six patients met the study inclusion criteria. Status at transplantation was first CR (n=97), primary refractory sAML (n=30) or relapsed (n=19) sAML. Neutrophil engraftment was achieved in 118 patients while the remaining 25 patients (17%) failed to engraft. This include 13% of patients transplanted in first CR versus 30% of those transplanted with active disease (P=0.008)). Two-year incidences of relapse were 25% in first CR patients versus 36% in those with advanced disease (P=0.06) while 2-year incidences of nonrelapse mortality were 35% and 49% (P=0.03), respectively. At 2-year overall survival, leukemia-free survival and graft-versus-host disease (GVHD)-free relapse free survival were 42% versus 19% (P<0.001), 40% versus 16% (P<0.001), and 26% versus 12% (P=0.002) in first CR patients versus those with advanced disease, respectively. CONCLUSIONS We report here the first study of CBT in a large cohort of sAML patients. Main observation was that CBT rescued approximately 40% of patients with sAML in first CR. This article is protected by copyright. All rights reserved.