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Scientific article
Open access
English

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

Published inAnnals of hematology, vol. 100, no. 1, p. 209-216
Publication date2021-01
First online date2020-10-23
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 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.

eng
Keywords
  • Busulfan
  • Conditioning regimen
  • Cyclophosphamide
  • Hematopoietic cell transplantation
  • Liver toxicity
  • Adult
  • Aged
  • Busulfan / administration & dosage
  • Busulfan / adverse effects
  • Chemical and Drug Induced Liver Injury / diagnosis
  • Chemical and Drug Induced Liver Injury / mortality
  • Cyclophosphamide / administration & dosage
  • Cyclophosphamide / adverse effects
  • Drug Therapy, Combination
  • Female
  • Hematologic Neoplasms / drug therapy
  • Hematologic Neoplasms / mortality
  • Hematologic Neoplasms / therapy
  • Hematopoietic Stem Cell Transplantation / methods
  • Hematopoietic Stem Cell Transplantation / mortality
  • Humans
  • Immunosuppressive Agents / administration & dosage
  • Immunosuppressive Agents / adverse effects
  • Male
  • Middle Aged
  • Prospective Studies
  • Transplantation Conditioning / methods
  • Transplantation Conditioning / mortality
  • Transplantation, Homologous / methods
  • Transplantation, Homologous / mortality
  • Young Adult
Citation (ISO format)
SEYDOUX, Claire et al. Busulfan-cyclophosphamide versus cyclophosphamide-busulfan as conditioning regimen before allogeneic hematopoietic cell transplantation: a prospective randomized trial. In: Annals of hematology, 2021, vol. 100, n° 1, p. 209–216. doi: 10.1007/s00277-020-04312-y
Main files (1)
Article (Published version)
Secondary files (1)
Identifiers
ISSN of the journal0939-5555
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Creation10/12/2021 7:38:00 AM
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