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Impact of conditioning intensity in T-replete haplo-identical stem cell transplantation for acute leukemia: a report from the acute leukemia working party of the EBMT

BACKGROUND: Increasing numbers of patients are receiving haplo-identical stem cell transplantation (haplo-SCT) for treatment of acute leukemia with reduced intensity (RIC) or myeloablative (MAC) conditioning regimens. The impact of conditioning intensity in haplo-SCT is unknown. METHODS: We performe...

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Autores principales: Rubio, Marie T., Savani, Bipin N., Labopin, Myriam, Piemontese, Simona, Polge, Emmanuelle, Ciceri, Fabio, Bacigalupo, Andrea, Arcese, William, Koc, Yener, Beelen, Dietrich, Gülbas, Zafer, Wu, Depei, Santarone, Stella, Tischer, Johanna, Afanasyev, Boris, Schmid, Christoph, Giebel, Sebastian, 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/PMC4791867/
https://www.ncbi.nlm.nih.gov/pubmed/26980295
http://dx.doi.org/10.1186/s13045-016-0248-3
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author Rubio, Marie T.
Savani, Bipin N.
Labopin, Myriam
Piemontese, Simona
Polge, Emmanuelle
Ciceri, Fabio
Bacigalupo, Andrea
Arcese, William
Koc, Yener
Beelen, Dietrich
Gülbas, Zafer
Wu, Depei
Santarone, Stella
Tischer, Johanna
Afanasyev, Boris
Schmid, Christoph
Giebel, Sebastian
Mohty, Mohamad
Nagler, Arnon
author_facet Rubio, Marie T.
Savani, Bipin N.
Labopin, Myriam
Piemontese, Simona
Polge, Emmanuelle
Ciceri, Fabio
Bacigalupo, Andrea
Arcese, William
Koc, Yener
Beelen, Dietrich
Gülbas, Zafer
Wu, Depei
Santarone, Stella
Tischer, Johanna
Afanasyev, Boris
Schmid, Christoph
Giebel, Sebastian
Mohty, Mohamad
Nagler, Arnon
author_sort Rubio, Marie T.
collection PubMed
description BACKGROUND: Increasing numbers of patients are receiving haplo-identical stem cell transplantation (haplo-SCT) for treatment of acute leukemia with reduced intensity (RIC) or myeloablative (MAC) conditioning regimens. The impact of conditioning intensity in haplo-SCT is unknown. METHODS: We performed a retrospective registry-based study comparing outcomes after T-replete haplo-SCT for patients with acute myeloid (AML) or lymphoid leukemia (ALL) after RIC (n = 271) and MAC (n = 425). Regimens were classified as MAC or RIC based on published criteria. RESULTS: A combination of post-transplant cyclophosphamide (PT-Cy) with one calcineurin inhibitor and mycophenolate mofetil (PT-Cy-based regimen) for graft-versus-host disease (GVHD) prophylaxis was used in 66 (25 %) patients in RIC and 125 (32 %) in MAC groups. Patients of RIC group were older and had been transplanted more recently and more frequently for AML with active disease at transplant. Percentage of engraftment (90 vs. 92 %; p = 0.58) and day 100 grade II to IV acute GVHD (24 vs. 29 %, p = 0.23) were not different between RIC and MAC groups. Multivariable analyses, run separately in AML and ALL, showed a trend toward higher relapse incidence with RIC in comparison to MAC in AML (hazard ratio (HR) 1.34, p = 0.09), and no difference in both AML and ALL in terms of non-relapse mortality (NRM) chronic GVHD and leukemia-free survival. There was no impact of conditioning regimen intensity in overall survival (OS) in AML (HR = 0.97, p = 0.79) but a trend for worse OS with RIC in ALL (HR = 1.44, p = 0.10). The main factor impacting outcomes was disease status at transplantation (HR ≥ 1.4, p ≤ 0.01). GVHD prophylaxis with PT-Cy-based regimen was independently associated with reduced NRM (HR 0.63, p = 0.02) without impact on relapse incidence (HR 0.99, p = 0.94). CONCLUSIONS: These data suggest that T-replete haplo-SCT with both RIC and MAC, in particular associated with PT-Cy, are valid options in first line treatment of high risk AML or ALL. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s13045-016-0248-3) contains supplementary material, which is available to authorized users.
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spelling pubmed-47918672016-03-16 Impact of conditioning intensity in T-replete haplo-identical stem cell transplantation for acute leukemia: a report from the acute leukemia working party of the EBMT Rubio, Marie T. Savani, Bipin N. Labopin, Myriam Piemontese, Simona Polge, Emmanuelle Ciceri, Fabio Bacigalupo, Andrea Arcese, William Koc, Yener Beelen, Dietrich Gülbas, Zafer Wu, Depei Santarone, Stella Tischer, Johanna Afanasyev, Boris Schmid, Christoph Giebel, Sebastian Mohty, Mohamad Nagler, Arnon J Hematol Oncol Research BACKGROUND: Increasing numbers of patients are receiving haplo-identical stem cell transplantation (haplo-SCT) for treatment of acute leukemia with reduced intensity (RIC) or myeloablative (MAC) conditioning regimens. The impact of conditioning intensity in haplo-SCT is unknown. METHODS: We performed a retrospective registry-based study comparing outcomes after T-replete haplo-SCT for patients with acute myeloid (AML) or lymphoid leukemia (ALL) after RIC (n = 271) and MAC (n = 425). Regimens were classified as MAC or RIC based on published criteria. RESULTS: A combination of post-transplant cyclophosphamide (PT-Cy) with one calcineurin inhibitor and mycophenolate mofetil (PT-Cy-based regimen) for graft-versus-host disease (GVHD) prophylaxis was used in 66 (25 %) patients in RIC and 125 (32 %) in MAC groups. Patients of RIC group were older and had been transplanted more recently and more frequently for AML with active disease at transplant. Percentage of engraftment (90 vs. 92 %; p = 0.58) and day 100 grade II to IV acute GVHD (24 vs. 29 %, p = 0.23) were not different between RIC and MAC groups. Multivariable analyses, run separately in AML and ALL, showed a trend toward higher relapse incidence with RIC in comparison to MAC in AML (hazard ratio (HR) 1.34, p = 0.09), and no difference in both AML and ALL in terms of non-relapse mortality (NRM) chronic GVHD and leukemia-free survival. There was no impact of conditioning regimen intensity in overall survival (OS) in AML (HR = 0.97, p = 0.79) but a trend for worse OS with RIC in ALL (HR = 1.44, p = 0.10). The main factor impacting outcomes was disease status at transplantation (HR ≥ 1.4, p ≤ 0.01). GVHD prophylaxis with PT-Cy-based regimen was independently associated with reduced NRM (HR 0.63, p = 0.02) without impact on relapse incidence (HR 0.99, p = 0.94). CONCLUSIONS: These data suggest that T-replete haplo-SCT with both RIC and MAC, in particular associated with PT-Cy, are valid options in first line treatment of high risk AML or ALL. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s13045-016-0248-3) contains supplementary material, which is available to authorized users. BioMed Central 2016-03-15 /pmc/articles/PMC4791867/ /pubmed/26980295 http://dx.doi.org/10.1186/s13045-016-0248-3 Text en © Rubio et al. 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
Piemontese, Simona
Polge, Emmanuelle
Ciceri, Fabio
Bacigalupo, Andrea
Arcese, William
Koc, Yener
Beelen, Dietrich
Gülbas, Zafer
Wu, Depei
Santarone, Stella
Tischer, Johanna
Afanasyev, Boris
Schmid, Christoph
Giebel, Sebastian
Mohty, Mohamad
Nagler, Arnon
Impact of conditioning intensity in T-replete haplo-identical stem cell transplantation for acute leukemia: a report from the acute leukemia working party of the EBMT
title Impact of conditioning intensity in T-replete haplo-identical stem cell transplantation for acute leukemia: a report from the acute leukemia working party of the EBMT
title_full Impact of conditioning intensity in T-replete haplo-identical stem cell transplantation for acute leukemia: a report from the acute leukemia working party of the EBMT
title_fullStr Impact of conditioning intensity in T-replete haplo-identical stem cell transplantation for acute leukemia: a report from the acute leukemia working party of the EBMT
title_full_unstemmed Impact of conditioning intensity in T-replete haplo-identical stem cell transplantation for acute leukemia: a report from the acute leukemia working party of the EBMT
title_short Impact of conditioning intensity in T-replete haplo-identical stem cell transplantation for acute leukemia: a report from the acute leukemia working party of the EBMT
title_sort impact of conditioning intensity in t-replete haplo-identical stem cell transplantation for acute leukemia: a report from the acute leukemia working party of the ebmt
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4791867/
https://www.ncbi.nlm.nih.gov/pubmed/26980295
http://dx.doi.org/10.1186/s13045-016-0248-3
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