Comparison of Conditioning with Fludarabine/Busulfan and Fludarabine/Melphalan in Allogeneic Transplantation Recipients 50 Years or Older

Biol Blood Marrow Transplant. 2017 Dec;23(12):2079-2087. doi: 10.1016/j.bbmt.2017.09.003. Epub 2017 Sep 7.

Abstract

The optimal conditioning regimen for elderly patients undergoing allogeneic hematopoietic stem cell transplantation (allo-HCT) remains unclear. We retrospectively analyzed 1607 patients aged 50 years or older with acute myeloid leukemia (AML), acute lymphoblastic leukemia, or myelodysplastic syndrome (MDS) who underwent allo-HCT using fludarabine/busulfan (FB) or fludarabine/melphalan (FM) between 2007 and 2014. We compared the clinical outcomes among FB2 (busulfan at 6.4 mg/kg iv, n = 463), FB4 (busulfan at 12.8 mg/kg iv, n = 721), and FM140 (melphalan at 140 mg/m2, n = 423). The nonrelapse mortality (NRM) rates in the FB4 and FM140 groups were higher than that in the FB2 group (hazard ratio [HR], 1.63 [P < .001]; and HR, 1.71 [P < .001], respectively). Conversely, the relapse rates in the FB4 and FM140 groups were lower than that in the FB2 group (HR, .73 [P = .011]; and HR, .56 [P < .001], respectively). There were no significant differences in overall survival (OS) among the FB2, FB4, and FM140 groups. The 3-year OS in patients with high-risk AML and MDS in the FM140 group (37.0% and 60.2%) were superior to those in the FB2 group (24.4% and 45.5%) and the FB4 group (24.6% and 40.6%) (P = .016 and P = .023), whereas there were no differences in OS in the other patients among the 3 groups. In conclusion, the lower rates of relapse in the FB4 and FM140 groups were largely offset by a worse NRM. However, FM140 might be associated with better OS in patients with high-risk AML and MDS.

Keywords: Allogeneic transplantation; Fludarabine/busulfan; Fludarabine/melphalan; Reduced-intensity conditioning regimen; Reduced-toxicity conditioning regimen.

Publication types

  • Comparative Study

MeSH terms

  • Aged
  • Aged, 80 and over
  • Busulfan / therapeutic use*
  • Drug Therapy, Combination
  • Female
  • Humans
  • Leukemia, Myeloid, Acute / mortality
  • Leukemia, Myeloid, Acute / therapy
  • Male
  • Melphalan / therapeutic use*
  • Middle Aged
  • Myelodysplastic Syndromes / mortality
  • Myelodysplastic Syndromes / therapy
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma / mortality
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma / therapy
  • Retrospective Studies
  • Survival Analysis
  • Transplantation Conditioning / methods*
  • Transplantation Conditioning / mortality
  • Transplantation Conditioning / standards
  • Transplantation, Homologous
  • Treatment Outcome
  • Vidarabine / analogs & derivatives*
  • Vidarabine / therapeutic use

Substances

  • Vidarabine
  • Busulfan
  • fludarabine
  • Melphalan