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Similar efficacy outcomes with peripheral blood stem cell versus bone marrow for autologous stem cell transplantation in acute myeloid leukemia: Long-term follow-up of the EORTC-GIMEMA randomized AML-10 trial
Baron, F., Efficace, F., Cannella, L., Stevens-Kroef, M., Amadori, S., de Witte, T., Lübbert, M., Venditti, A., Suciu, S.
American journal of hematology. 2024
Abstract
We report here the long-term follow-up of the only prospective randomized trial of autologous hematopoietic stem cell transplantation (auto-HSCT) with peripheral blood stem cells (APBSCT) versus auto-HSCT with bone marrow (ABMT) in acute myeloid leukemia (AML) patients in first remission (CR). We observed that among patients alive and still in CR 5 years after planned auto-HSCT, approximately 10% of the patients died in the following 10 years. This stresses the need for long-term close surveillance of AML patients after auto-HSCT. Further, long-term follow-up of the trial confirms that APBSCT was comparable to ABMT in term of disease-free-survival and overall survival.
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Advantages of peripheral blood stem cells from unrelated donors versus bone marrow transplants in outcomes of adult acute myeloid leukemia patients
Jo, T., Arai, Y., Kondo, T., Mizuno, S., Hirabayashi, S., Inamoto, Y., Doki, N., Fukuda, T., Ozawa, Y., Katayama, Y., et al
Cytotherapy. 2022
Abstract
BACKGROUND AIMS In allogeneic stem cell transplantation, unrelated donors are chosen in cases where appropriate related donors are not available. Peripheral blood stem cells (PBSCs) are more often selected as a graft source than bone marrow (BM). However, the prognostic benefits of PBSCs versus BM transplants from unrelated donors have not been carefully examined in patients with acute myeloid leukemia (AML). This study compared outcomes of adult AML patients who underwent unrelated PBSC and BM transplantation, evaluating post-transplant complications, including engraftment, graft-versus-host disease (GVHD) and infections, and determined subgroups of patients who are most likely to benefit from unrelated PBSCs compared with BM transplants. METHODS The authors analyzed 2962 adult AML patients who underwent unrelated PBSC or BM transplants between 2011 and 2018 (221 PBSC and 2741 BM) using the Japanese nationwide registry database, in which graft source selection is not skewed toward PBSCs. RESULTS In 49.7% of patients, disease status at transplantation was first complete remission (CR1). In 57.1% of cases, HLA-matched donors were selected. Myeloablative conditioning was performed in 75.1% of cases, and anti-thymocyte globulin (ATG) was added to conditioning in 10.5%. Multivariate analyses showed a trend toward favorable non-relapse mortality (NRM) in PBSC recipients compared with BM recipients (hazard ratio [HR], 0.731, P = 0.096), whereas overall survival (OS) (HR, 0.959, P = 0.230) and disease-free survival (DFS) (HR, 0.868, P = 0.221) were comparable between PBSC and BM recipients. Although the rate of chronic GVHD (cGVHD) was significantly higher in PBSC patients (HR, 1.367, P = 0.016), NRM was not increased, mainly as a result of significantly reduced risk of bacterial infections (HR, 0.618, P = 0.010), reflecting more prompt engraftments in PBSC recipients. Subgroup analyses revealed that PBSC transplantation was advantageous in patients transplanted at CR1 and in those without ATG use. PBSC recipients experienced significantly better OS and/or DFS compared with BM recipients in this patient group. CONCLUSIONS The authors' results confirmed the overall safety of unrelated PBSC transplantation for adult AML patients and suggested an advantage of PBSCs, especially for those in CR1. Further optimization of the prophylactic strategy for cGVHD is required to improve the overall outcome in transplantation from unrelated PBSC donors.
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HLA-haploidentical transplantation for relapsed/refractory AML: better LFS with BM than with PBSC in patients ≥ 55 years of age
Baron, F., Labopin, M., Tischer, J., Ciceri, F., Raiola, A. M., Blaise, D., Sica, S., Vydra, J., Fanin, R., Stölzel, F., et al
American journal of hematology. 2022
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Abstract
The best stem cell source for T-cell replete HLA-haploidentical transplantation with post-transplant cyclophosphamide (PTCy) remains to be determined. In this EBMT retrospective study we analyzed the impact of stem cell source on leukemia-free survival (LFS) in adult patients with primary refractory or relapsed acute myeloid leukemia (AML) given grafts from HLA-haploidentical donors with PTCy as graft-versus-host disease (GVHD) prophylaxis. A total of 668 patients (249 bone marrow (BM) and 419 peripheral blood stem cells (PBSC) recipients) met the inclusion criteria. The use of PBSC was associated with a higher incidence of grade II-IV (HR = 1.59, P = 0.029) and grade III-IV (HR = 2.08, P = 0.013) acute GVHD. There was a statistical interaction between patient age and the impact of stem cell source for LFS (P < 0.01). In multivariate Cox models, among patients <55 years, the use of PBSC versus BM resulted in comparable LFS (HR = 0.82, P = 0.2). In contrast, in patients ≥55 years of age, the use of PBSC versus BM was associated with higher non-relapse mortality (NRM) (HR = 1.7, P = 0.01), lower LFS (HR = 1.37, P = 0.026) and lower overall survival (OS) (HR = 1.33, P = 0.044). In conclusions, our data suggest that in patients ≥55 years of age with active AML at HLA-haploidentical transplantation, the use of BM instead of PBSC as stem cell source results in lower NRM and better LFS. In contrast among younger patients, the use of PBSC results in at least a comparable LFS. This article is protected by copyright. All rights reserved.
PICO Summary
Population
Adults with primary refractory or relapsed acute myeloid leukaemia receiving haploidentical transplantation (n=668)
Intervention
Stem cell graft sourced from peripheral blood stem (PBSC, n=419)
Comparison
Stem cell graft sourced from bone marrow (BM, n=249)
Outcome
The use of PBSC was associated with a higher incidence of grade II-IV (HR = 1.59) and grade III-IV (HR = 2.08) acute GVHD. There was a statistical interaction between patient age and the impact of stem cell source for LFS. In multivariate Cox models, among patients <55 years, the use of PBSC versus BM resulted in comparable LFS (HR = 0.82). In contrast, in patients ≥55 years of age, the use of PBSC versus BM was associated with higher non-relapse mortality (NRM) (HR = 1.7), lower LFS (HR = 1.37) and lower overall survival (OS) (HR = 1.33).
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Time-Varying Effects of Graft Type on Outcomes for Patients with Acute Myeloid Leukemia Undergoing Allogeneic Hematopoietic Cell Transplantation
Yanada, M., Konuma, T., Yamasaki, S., Kuwatsuka, Y., Masuko, M., Tanaka, M., Ozawa, Y., Toya, T., Fukuda, T., Ota, S., et al
Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation. 2019
Abstract
This study aimed to investigate time-varying effects of graft type on outcomes for patients with acute myeloid leukemia (AML) undergoing allogeneic hematopoietic cell transplantation. For this purpose, we analyzed 3952 patients comprising 720 of whom underwent matched related bone marrow transplantation (BMT), 1004 matched related peripheral blood stem cell transplantation (PBSCT), 856 matched unrelated BMT, and 1372 umbilical cord blood transplantation (UCBT). The 4-year relapse-free survival (RFS) rates were 59.1%, 52.8%, 59.5%, and 50.6%, respectively. Compared to related BMT, related PBSCT, unrelated BMT and UCBT were associated with higher risk of non-relapse mortality, and unrelated BMT and UCBT with lower risk of relapse. As a result, both RFS and overall survival (OS) were comparable between related BMT and unrelated BMT, but were worse for related PBSCT and UCBT than for related BMT. Adverse impact of UCBT was observed only during the early phase of transplantation, whereas that of related PBSCT continued even after two years post-transplant. Our findings raise concerns about the increased risk of late non-relapse mortality with the use of PBSC grafts, and suggest that related BMT is preferable to related PBSCT, and matched unrelated BMT is the next choice in the absence of a matched related donor.
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More chronic GvHD and non-relapse mortality after peripheral blood stem cell compared with bone marrow in hematopoietic transplantation for paediatric acute lymphoblastic leukemia: a retrospective study on behalf of the EBMT Paediatric Diseases Working Party
Simonin, M., Dalissier, A., Labopin, M., Willasch, A., Zecca, M., Mouhab, A., Chybicka, A., Balduzzi, A., Volin, L., Peters, C., et al
Bone Marrow Transplantation. 2017;52(7):1071-1073
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Peripheral blood stem cell graft compared to bone marrow after reduced intensity conditioning regimens for acute leukemia: a report from the ALWP of the EBMT
Savani, B. N., Labopin, M., Blaise, D., Niederwieser, D., Ciceri, F., Ganser, A., Arnold, R., Afanasyev, B., Vigouroux, S., Milpied, N., et al
Haematologica. 2016;101(2):256-62
Abstract
Increasing numbers of patients are receiving reduced intensity conditioning regimen allogeneic hematopoietic stem cell transplantation. We hypothesized that the use of bone marrow graft might decrease the risk of graft-versus-host disease compared to peripheral blood after reduced intensity conditioning regimens without compromising graft-versus-leukemia effects. Patients who underwent reduced intensity conditioning regimen allogeneic hematopoietic stem cell transplantation from 2000 to 2012 for acute leukemia, and who were reported to the Acute Leukemia Working Party of the European Group for Blood and Marrow Transplantation were included in the study. Eight hundred and thirty-seven patients receiving bone marrow grafts were compared with 9011 peripheral blood transplant recipients after reduced intensity conditioning regimen. Median follow up of surviving patients was 27 months. Cumulative incidence of engraftment (neutrophil >0.5x10(9)/L at day 60) was lower in bone marrow recipients: 88% versus 95% (P<0.0001). Grade II to IV acute graft-versus-host disease was lower in bone marrow recipients: 19% versus 24% for peripheral blood (P=0.005). In multivariate analysis, after adjusting for differences between both groups, overall survival [Hazard Ratio (HR) 0.90; P=0.05] and leukemia-free survival (HR 0.88; P=0.01) were higher in patients transplanted with peripheral blood compared to bone marrow grafts. Furthermore, peripheral blood graft was also associated with decreased risk of relapse (HR 0.78; P=0.0001). There was no significant difference in non-relapse mortality between recipients of bone marrow and peripheral blood grafts, and chronic graft-versus-host disease was significantly higher after peripheral blood grafts (HR 1.38; P<0.0001). Despite the limitation of a retrospective registry-based study, we found that peripheral blood grafts after reduced intensity conditioning regimens had better overall and leukemia-free survival than bone marrow grafts. However, there is an increase in chronic graft-versus-host disease after peripheral blood grafts. Long-term follow up is needed to clarify whether chronic graft-versus-host disease might increase the risk of late morbidity and mortality. Copyright© Ferrata Storti Foundation.