Choosing a Reduced-Intensity Conditioning Regimen for Allogeneic Stem Cell Transplantation, Fludarabine/Busulfan versus Fludarabine Melphalan: A Systematic Review and Meta-Analysis

Biol Blood Marrow Transplant. 2019 Apr;25(4):728-733. doi: 10.1016/j.bbmt.2018.11.016. Epub 2018 Nov 22.

Abstract

Fludarabine with busulfan (FB) or melphalan (FM) are 2 more commonly used reduced-intensity conditioning (RIC) regimens for allogeneic stem cell transplantation (HCT).We present a systematic review and meta-analysis of studies comparing these 2 RIC regimens. We searched electronic databases from inception through November 1, 2017 for literature searches to identify relevant studies. A DerSimonian random effects model was used to measure efficacy outcomes; hazard ratios (HRs) and corresponding 95% confidence intervals (CIs) are reported. Seven studies, including a total of 1955 patients, met criteria for inclusion, of which 6 were included in the overall pooled analysis because of repetition of some patients in 2 studies. Three studies were included in the subgroup analysis of acute myelogenous leukemia (AML)/myelodysplastic syndrome (MDS) and 2 in the subgroup analysis of lymphoid malignancies. Overall survival (OS) and progression-free survival were not statistically significantly different between the 2 RIC regimens in analysis of all studies. However, OS was better with FM in subgroup analysis of AML/MDS studies (HR, .83; 95% CI, .73 to .95). Nonrelapse mortality was lower with FB (HR, .64; 95% CI, .46 to .89), whereas relapse was lower with FM (HR, 1.52; 95% CI, 1.13 to 2.06) in the analysis of all studies. This meta-analysis shows that FB and FM are associated with a similar OS in patients undergoing HCT. Relapse rates are lower with FM but at the cost of higher nonrelapse mortality.

Keywords: Busulfan; Fludarabine; Melphalan; Reduced-intensity conditioning.

Publication types

  • Meta-Analysis
  • Systematic Review

MeSH terms

  • Busulfan / pharmacology
  • Busulfan / therapeutic use*
  • Female
  • Hematopoietic Stem Cell Transplantation / methods*
  • Humans
  • Immunosuppressive Agents / pharmacology
  • Immunosuppressive Agents / therapeutic use*
  • Male
  • Melphalan / pharmacology
  • Melphalan / therapeutic use*
  • Transplantation Conditioning / methods*
  • Transplantation, Homologous / methods*
  • Vidarabine / analogs & derivatives*
  • Vidarabine / pharmacology
  • Vidarabine / therapeutic use

Substances

  • Immunosuppressive Agents
  • Vidarabine
  • Busulfan
  • fludarabine
  • Melphalan