Busulfan-cyclophosphamide versus cyclophosphamide-busulfan as conditioning regimen before allogeneic hematopoietic cell
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ORIGINAL ARTICLE
Busulfan-cyclophosphamide versus cyclophosphamide-busulfan as conditioning regimen before allogeneic hematopoietic cell transplantation: a prospective randomized trial Claire Seydoux 1 & Michael Medinger 1 & Sabine Gerull 1 & Joerg Halter 1 & Dominik Heim 1 & Yves Chalandon 2 & Stavroula Masouridi Levrat 2 & Urs Schanz 3 & Gayathri Nair 3 & Marc Ansari 4,5 & Patrick Simon 6 & Jakob R. Passweg 1 & Nathan Cantoni 7 Received: 26 September 2020 / Accepted: 15 October 2020 # The Author(s) 2020
Abstract 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 cyclophosphamidebusulfan (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. Keywords Busulfan . Conditioning regimen . Cyclophosphamide . Hematopoietic cell transplantation . Liver toxicity
Claire Seydoux and Michael Medinger contributed equally to this work. Electronic supplementary material The online version of this article (https://doi.org/10.1007/s00277-020-04312-y) contains supplementary material, which is available to authorized users. * Michael Medinger [email protected] * Jakob R. Passweg [email protected] 1
2
Divisions of Hematology and Internal Medicine, Department of Medicine, University Hospital of Basel, Petersgraben 4, CH-4031 Basel, Switzerland Division of Hematology, Bone Marrow Transplant Unit, University Hospital of Geneva and Faculty of Medicine, University of Geneva, Geneva, Switzerland
3
Department of Medical Oncology and Hematology, Stem-/Immunecell-transplant Unit, University Hospital of Zurich, Zurich, Switzerland
4
Department Women, Children and Adolescent, Unit of Oncology and Hematology Pediatric, University Hospital of Geneva, Geneva, Switzerland
5
Cansearch Research Laboratory, Faculty of Medicine, University of Geneva, Geneva, Switzerland
6
Clinical Trials Unit, Department of Clinical Research, Basel University, Basel
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