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The impact of HLA-matching on reduced intensity conditioning regimen unrelated donor allogeneic stem cell transplantation for acute myeloid leukemia in patients above 50 years—a report from the EBMT acute leukemia working party

BACKGROUND: Data comparing fully matched and mismatched-unrelated-donor (M- and mM-URD) allogeneic hematopoietic stem cell transplant (allo-SCT) following reduced intensity conditioning regimens for acute myeloid leukemia are limited. METHODS: We retrospectively compared the outcome of 3398 patients...

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Autores principales: Rubio, Marie T., Savani, Bipin N., Labopin, Myriam, Polge, Emmanuelle, Niederwieser, Dietger, Ganser, Arnold, Schwerdtfeger, Rainer, Ehninger, Gerhard, Finke, Jürgen, Renate, Arnold, Craddock, Charles, Kröger, Nicolaus, Hallek, Michael, Jindra, Pavel, Mohty, Mohamad, Nagler, Arnon
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4971653/
https://www.ncbi.nlm.nih.gov/pubmed/27488518
http://dx.doi.org/10.1186/s13045-016-0295-9
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author Rubio, Marie T.
Savani, Bipin N.
Labopin, Myriam
Polge, Emmanuelle
Niederwieser, Dietger
Ganser, Arnold
Schwerdtfeger, Rainer
Ehninger, Gerhard
Finke, Jürgen
Renate, Arnold
Craddock, Charles
Kröger, Nicolaus
Hallek, Michael
Jindra, Pavel
Mohty, Mohamad
Nagler, Arnon
author_facet Rubio, Marie T.
Savani, Bipin N.
Labopin, Myriam
Polge, Emmanuelle
Niederwieser, Dietger
Ganser, Arnold
Schwerdtfeger, Rainer
Ehninger, Gerhard
Finke, Jürgen
Renate, Arnold
Craddock, Charles
Kröger, Nicolaus
Hallek, Michael
Jindra, Pavel
Mohty, Mohamad
Nagler, Arnon
author_sort Rubio, Marie T.
collection PubMed
description BACKGROUND: Data comparing fully matched and mismatched-unrelated-donor (M- and mM-URD) allogeneic hematopoietic stem cell transplant (allo-SCT) following reduced intensity conditioning regimens for acute myeloid leukemia are limited. METHODS: We retrospectively compared the outcome of 3398 patients above the age of 50 years who underwent 10/10 M-URD (n = 2567), 9/10 (n = 723), or 8/10 (n = 108) mM-URD allo-SCT for acute myeloid leukemia after reduced intensity conditioning regimen between 2000 and 2013. The Kaplan-Meier estimator, the cumulative incidence function, and Cox proportional hazards regression models were used where appropriate. RESULTS: HLA matching had no impact on engraftment (p = 0.31). In univariate analysis, in comparison to 10/10 M-URD, mM-URD was associated with higher incidence of grade II–IV acute graft-versus-host disease (GVHD) (p = 0.0002), similar rates of chronic GVHD (p = 0.138) but increased incidence of its extensive form (p = 0.047). Compared to 10/10 M-URD, patients transplanted in the first complete remission (CR1) with a 9 or an 8/10 mM-URD had decreased 2-year leukemia free (LFS) (p = 0.005) and overall survivals (OS) (56.7, 46.1, and 50.2 %, respectively, p = 0.005), while outcomes were comparable between all groups for patients transplanted beyond CR1. In multivariate analysis, 9/10 versus 10/10 URD was associated with higher non-relapse mortality (HR 1.34, p = 0.001), similar risk of relapse and chronic GVHD and inferior LFS (HR 1.25, p = 0.0001), and OS (HR 1.27, p = 0.0001). There was no difference in adjusted transplant outcomes between 9/10 and 8/10 mM-URD. CONCLUSIONS: Reduced intensity conditioned allo-SCT with a 10/10 M-URD remains the preferable option for AML patients above the age of 50 years. The use of a 9/10 or an 8/10 mM-URD in patients not having a fully matched donor represents an alternative therapeutic option that should be compared to other alternative donor transplant strategies. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s13045-016-0295-9) contains supplementary material, which is available to authorized users.
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spelling pubmed-49716532016-08-04 The impact of HLA-matching on reduced intensity conditioning regimen unrelated donor allogeneic stem cell transplantation for acute myeloid leukemia in patients above 50 years—a report from the EBMT acute leukemia working party Rubio, Marie T. Savani, Bipin N. Labopin, Myriam Polge, Emmanuelle Niederwieser, Dietger Ganser, Arnold Schwerdtfeger, Rainer Ehninger, Gerhard Finke, Jürgen Renate, Arnold Craddock, Charles Kröger, Nicolaus Hallek, Michael Jindra, Pavel Mohty, Mohamad Nagler, Arnon J Hematol Oncol Research BACKGROUND: Data comparing fully matched and mismatched-unrelated-donor (M- and mM-URD) allogeneic hematopoietic stem cell transplant (allo-SCT) following reduced intensity conditioning regimens for acute myeloid leukemia are limited. METHODS: We retrospectively compared the outcome of 3398 patients above the age of 50 years who underwent 10/10 M-URD (n = 2567), 9/10 (n = 723), or 8/10 (n = 108) mM-URD allo-SCT for acute myeloid leukemia after reduced intensity conditioning regimen between 2000 and 2013. The Kaplan-Meier estimator, the cumulative incidence function, and Cox proportional hazards regression models were used where appropriate. RESULTS: HLA matching had no impact on engraftment (p = 0.31). In univariate analysis, in comparison to 10/10 M-URD, mM-URD was associated with higher incidence of grade II–IV acute graft-versus-host disease (GVHD) (p = 0.0002), similar rates of chronic GVHD (p = 0.138) but increased incidence of its extensive form (p = 0.047). Compared to 10/10 M-URD, patients transplanted in the first complete remission (CR1) with a 9 or an 8/10 mM-URD had decreased 2-year leukemia free (LFS) (p = 0.005) and overall survivals (OS) (56.7, 46.1, and 50.2 %, respectively, p = 0.005), while outcomes were comparable between all groups for patients transplanted beyond CR1. In multivariate analysis, 9/10 versus 10/10 URD was associated with higher non-relapse mortality (HR 1.34, p = 0.001), similar risk of relapse and chronic GVHD and inferior LFS (HR 1.25, p = 0.0001), and OS (HR 1.27, p = 0.0001). There was no difference in adjusted transplant outcomes between 9/10 and 8/10 mM-URD. CONCLUSIONS: Reduced intensity conditioned allo-SCT with a 10/10 M-URD remains the preferable option for AML patients above the age of 50 years. The use of a 9/10 or an 8/10 mM-URD in patients not having a fully matched donor represents an alternative therapeutic option that should be compared to other alternative donor transplant strategies. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s13045-016-0295-9) contains supplementary material, which is available to authorized users. BioMed Central 2016-08-03 /pmc/articles/PMC4971653/ /pubmed/27488518 http://dx.doi.org/10.1186/s13045-016-0295-9 Text en © The Author(s). 2016 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
spellingShingle Research
Rubio, Marie T.
Savani, Bipin N.
Labopin, Myriam
Polge, Emmanuelle
Niederwieser, Dietger
Ganser, Arnold
Schwerdtfeger, Rainer
Ehninger, Gerhard
Finke, Jürgen
Renate, Arnold
Craddock, Charles
Kröger, Nicolaus
Hallek, Michael
Jindra, Pavel
Mohty, Mohamad
Nagler, Arnon
The impact of HLA-matching on reduced intensity conditioning regimen unrelated donor allogeneic stem cell transplantation for acute myeloid leukemia in patients above 50 years—a report from the EBMT acute leukemia working party
title The impact of HLA-matching on reduced intensity conditioning regimen unrelated donor allogeneic stem cell transplantation for acute myeloid leukemia in patients above 50 years—a report from the EBMT acute leukemia working party
title_full The impact of HLA-matching on reduced intensity conditioning regimen unrelated donor allogeneic stem cell transplantation for acute myeloid leukemia in patients above 50 years—a report from the EBMT acute leukemia working party
title_fullStr The impact of HLA-matching on reduced intensity conditioning regimen unrelated donor allogeneic stem cell transplantation for acute myeloid leukemia in patients above 50 years—a report from the EBMT acute leukemia working party
title_full_unstemmed The impact of HLA-matching on reduced intensity conditioning regimen unrelated donor allogeneic stem cell transplantation for acute myeloid leukemia in patients above 50 years—a report from the EBMT acute leukemia working party
title_short The impact of HLA-matching on reduced intensity conditioning regimen unrelated donor allogeneic stem cell transplantation for acute myeloid leukemia in patients above 50 years—a report from the EBMT acute leukemia working party
title_sort impact of hla-matching on reduced intensity conditioning regimen unrelated donor allogeneic stem cell transplantation for acute myeloid leukemia in patients above 50 years—a report from the ebmt acute leukemia working party
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4971653/
https://www.ncbi.nlm.nih.gov/pubmed/27488518
http://dx.doi.org/10.1186/s13045-016-0295-9
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