Impact of busulfan versus treosulfan dose intensity in myelofibrosis undergoing hematopoietic cell transplantation

Am J Hematol. 2024 Aug;99(8):1540-1549. doi: 10.1002/ajh.27363. Epub 2024 May 14.

Abstract

One key aspect of allogeneic hematopoietic cell transplantation (HCT) is pretransplant conditioning, balancing risk for relapse versus non-relapse mortality. Conditioning regimens with different alkylators at different doses can influence outcome, but data are missing for myelofibrosis, a challenging cohort of patients usually presenting at older age and with comorbidities. We evaluated in a multicenter retrospective study the comparative efficacy and safety of busulfan versus treosulfan in combination with fludarabine for myelofibrosis patients undergoing HCT. This study included 1115 patients (busulfan, n = 902; treosulfan, n = 213) receiving first HCT between 2005 and 2021. Patients were generally balanced for key patient characteristics. Overall survival at 4 years was 62% for the busulfan group versus 58% for the treosulfan group (p = .22). Impact on outcome was dose-dependent. Overall survival was 65% (95% CI, 61%-69%) for reduced intensity busulfan versus 69% (95% CI, 54%-84%) for reduced intensity treosulfan, 53% (95% CI, 44%-63%) for higher intensity busulfan, and 55% (95% CI, 46%-63%) for higher intensity treosulfan. Incidence of relapse was similar across intensity groups. In multivariable analysis, the hazard for death (with reduced intensity busulfan as reference) was 0.88 (95% CI, 0.39-2.01) for reduced intensity treosulfan (p = .77), 1.42 (95% CI, 0.96-2.10) for higher intensity busulfan (0.08), and 1.61 (95% CI, 1.14-2.26) for higher intensity treosulfan (p = .006). In terms of non-relapse mortality, comparison was not significantly different, while the hazard ratio for higher intensity treosulfan was 1.48 (95% CI, 0.98-2.23; p = .06). Here, we showed comparable outcomes and improved survival in myelofibrosis undergoing HCT with reduced intensity busulfan or treosulfan.

Publication types

  • Multicenter Study
  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Antineoplastic Agents, Alkylating / administration & dosage
  • Antineoplastic Agents, Alkylating / therapeutic use
  • Busulfan* / administration & dosage
  • Busulfan* / analogs & derivatives
  • Busulfan* / therapeutic use
  • Female
  • Hematopoietic Stem Cell Transplantation*
  • Humans
  • Male
  • Middle Aged
  • Primary Myelofibrosis* / drug therapy
  • Primary Myelofibrosis* / mortality
  • Primary Myelofibrosis* / therapy
  • Retrospective Studies
  • Transplantation Conditioning* / methods
  • Vidarabine* / administration & dosage
  • Vidarabine* / analogs & derivatives
  • Vidarabine* / therapeutic use
  • Young Adult

Substances

  • Busulfan
  • treosulfan
  • Vidarabine
  • fludarabine
  • Antineoplastic Agents, Alkylating