Busulfan-cyclophosphamide versus cyclophosphamide-busulfan as conditioning regimen before allogeneic hematopoietic cell transplantation: a prospective randomized trial

Busulfan and cyclophosphamide (BuCy) is a frequently used myeloablative conditioning regimen for allogeneic hematopoietic cell transplantation (allo-HCT). Theoretical considerations and pharmacological data indicate that application of busulfan prior to subsequent cyclophosphamide (BuCy) may trigger...

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Autores principales: Seydoux, Claire, Medinger, Michael, Gerull, Sabine, Halter, Joerg, Heim, Dominik, Chalandon, Yves, Levrat, Stavroula Masouridi, Schanz, Urs, Nair, Gayathri, Ansari, Marc, Simon, Patrick, Passweg, Jakob R., Cantoni, Nathan
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Springer Berlin Heidelberg 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7782401/
https://www.ncbi.nlm.nih.gov/pubmed/33098041
http://dx.doi.org/10.1007/s00277-020-04312-y
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author Seydoux, Claire
Medinger, Michael
Gerull, Sabine
Halter, Joerg
Heim, Dominik
Chalandon, Yves
Levrat, Stavroula Masouridi
Schanz, Urs
Nair, Gayathri
Ansari, Marc
Simon, Patrick
Passweg, Jakob R.
Cantoni, Nathan
author_facet Seydoux, Claire
Medinger, Michael
Gerull, Sabine
Halter, Joerg
Heim, Dominik
Chalandon, Yves
Levrat, Stavroula Masouridi
Schanz, Urs
Nair, Gayathri
Ansari, Marc
Simon, Patrick
Passweg, Jakob R.
Cantoni, Nathan
author_sort Seydoux, Claire
collection PubMed
description Busulfan and cyclophosphamide (BuCy) is a frequently used myeloablative conditioning regimen for allogeneic hematopoietic cell transplantation (allo-HCT). Theoretical considerations and pharmacological data indicate that application of busulfan prior to subsequent cyclophosphamide (BuCy) may trigger liver toxicity. Reversing the order of application to cyclophosphamide-busulfan (CyBu) might be preferable, a hypothesis supported by animal data and retrospective studies. We performed a prospective randomized trial to determine impact of order of application of Bu and Cy before allo-HCT in 70 patients with hematological malignancy, 33 patients received BuCy and 37 CyBu for conditioning. In the short term, there were minimal differences in liver toxicity favoring CyBu over BuCy, significant only for alanine amino transferase at day 30 (p = 0.03). With longer follow-up at 4 years, non-relapse mortality (6% versus 27%, p = 0.05) was lower and survival (63% versus 43%, p = 0.06) was higher with CyBu compared to BuCy. Other outcomes, such as engraftment (p = 0.21), acute and chronic graft-versus-host disease (p = 0.40; 0.36), and relapse (p = 0.79), were similar in both groups. We prospectively show evidence that the order of application of Cy and Bu in myeloablative conditioning in allo-HCT patients has impact on outcome. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s00277-020-04312-y) contains supplementary material, which is available to authorized users.
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spelling pubmed-77824012021-01-11 Busulfan-cyclophosphamide versus cyclophosphamide-busulfan as conditioning regimen before allogeneic hematopoietic cell transplantation: a prospective randomized trial Seydoux, Claire Medinger, Michael Gerull, Sabine Halter, Joerg Heim, Dominik Chalandon, Yves Levrat, Stavroula Masouridi Schanz, Urs Nair, Gayathri Ansari, Marc Simon, Patrick Passweg, Jakob R. Cantoni, Nathan Ann Hematol Original Article Busulfan and cyclophosphamide (BuCy) is a frequently used myeloablative conditioning regimen for allogeneic hematopoietic cell transplantation (allo-HCT). Theoretical considerations and pharmacological data indicate that application of busulfan prior to subsequent cyclophosphamide (BuCy) may trigger liver toxicity. Reversing the order of application to cyclophosphamide-busulfan (CyBu) might be preferable, a hypothesis supported by animal data and retrospective studies. We performed a prospective randomized trial to determine impact of order of application of Bu and Cy before allo-HCT in 70 patients with hematological malignancy, 33 patients received BuCy and 37 CyBu for conditioning. In the short term, there were minimal differences in liver toxicity favoring CyBu over BuCy, significant only for alanine amino transferase at day 30 (p = 0.03). With longer follow-up at 4 years, non-relapse mortality (6% versus 27%, p = 0.05) was lower and survival (63% versus 43%, p = 0.06) was higher with CyBu compared to BuCy. Other outcomes, such as engraftment (p = 0.21), acute and chronic graft-versus-host disease (p = 0.40; 0.36), and relapse (p = 0.79), were similar in both groups. We prospectively show evidence that the order of application of Cy and Bu in myeloablative conditioning in allo-HCT patients has impact on outcome. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s00277-020-04312-y) contains supplementary material, which is available to authorized users. Springer Berlin Heidelberg 2020-10-23 2021 /pmc/articles/PMC7782401/ /pubmed/33098041 http://dx.doi.org/10.1007/s00277-020-04312-y Text en © The Author(s) 2020 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.
spellingShingle Original Article
Seydoux, Claire
Medinger, Michael
Gerull, Sabine
Halter, Joerg
Heim, Dominik
Chalandon, Yves
Levrat, Stavroula Masouridi
Schanz, Urs
Nair, Gayathri
Ansari, Marc
Simon, Patrick
Passweg, Jakob R.
Cantoni, Nathan
Busulfan-cyclophosphamide versus cyclophosphamide-busulfan as conditioning regimen before allogeneic hematopoietic cell transplantation: a prospective randomized trial
title Busulfan-cyclophosphamide versus cyclophosphamide-busulfan as conditioning regimen before allogeneic hematopoietic cell transplantation: a prospective randomized trial
title_full Busulfan-cyclophosphamide versus cyclophosphamide-busulfan as conditioning regimen before allogeneic hematopoietic cell transplantation: a prospective randomized trial
title_fullStr Busulfan-cyclophosphamide versus cyclophosphamide-busulfan as conditioning regimen before allogeneic hematopoietic cell transplantation: a prospective randomized trial
title_full_unstemmed Busulfan-cyclophosphamide versus cyclophosphamide-busulfan as conditioning regimen before allogeneic hematopoietic cell transplantation: a prospective randomized trial
title_short Busulfan-cyclophosphamide versus cyclophosphamide-busulfan as conditioning regimen before allogeneic hematopoietic cell transplantation: a prospective randomized trial
title_sort busulfan-cyclophosphamide versus cyclophosphamide-busulfan as conditioning regimen before allogeneic hematopoietic cell transplantation: a prospective randomized trial
topic Original Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7782401/
https://www.ncbi.nlm.nih.gov/pubmed/33098041
http://dx.doi.org/10.1007/s00277-020-04312-y
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