Fludarabine-Busulfan Reduced-Intensity Conditioning in Comparison with Fludarabine-Melphalan Is Associated with Increased Relapse Risk In Spite of Pharmacokinetic Dosing

Moussab Damlaj, Hassan B. Alkhateeb, Mehrdad Hefazi, Daniel K. Partain, Shahrukh Hashmi, Dennis A. Gastineau, Aref Al-Kali, Robert C. Wolf, Naseema Gangat, Mark R Litzow, William Hogan, Mrinal M Patnaik

Research output: Contribution to journalArticle

13 Scopus citations

Abstract

Fludarabine with busulfan (FB) and fludarabine with melphalan (FM) are commonly used reduced-intensity conditioning (RIC) regimens. Pharmacokinetic dosing of busulfan (Bu) is frequently done for myeloablative conditioning, but evidence for its use is limited in RIC transplants. We compared transplant outcomes of FB versus FM using i.v. Bu targeted to the area under the curve (AUC). A total of 134 RIC transplants (47 FB and 87 FM) for acute myelogenous leukemia and myelodysplastic syndrome were identified, and median follow-up of the cohort was 40 months (range, 0 to 63.3). A significantly higher 2-year cumulative incidence of relapse (CIR) was associated with FB versus FM at 35.6% versus 17.3%, respectively (P = .0058). Furthermore, 2-year progression-free survival rates were higher for FM versus FB at 60.5% versus 48.7%, respectively (P = .04). However, 2-year rates of nonrelapse mortality (NRM) and overall survival (OS) were similar. The need for dose adjustment based on AUC did not alter relapse risk or NRM. Patients with Karnofsky performance status ≥ 90 who received FM had a 2-year OS rate of 74.8% versus 48.3% for FB (P = .03). FB use remained prognostic for relapse in multivariable analysis (hazard ratio, 2.75; 95% confidence interval, 1.28 to 5.89; P = .0097). In summary, in spite of AUC-directed dosing, FB compared with FM was associated with a significantly higher CIR.

Original languageEnglish (US)
Pages (from-to)1431-1439
Number of pages9
JournalBiology of Blood and Marrow Transplantation
Volume22
Issue number8
DOIs
StatePublished - Aug 1 2016

Keywords

  • Area under the curve
  • Fludarabine-busulfan
  • Fludarabine-melphalan
  • Myeloablative conditioning
  • Reduced intensity conditioning

ASJC Scopus subject areas

  • Medicine(all)
  • Hematology
  • Transplantation

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