Therapeutic drug monitoring for either oral or intravenous busulfan when combined with pre-and post-transplantation cyclophosphamide

Lindsey R. Lombardi, Christopher G. Kanakry, Marianna Zahurak, Nadira Durakovic, Javier Bolaños-Meade, Yvette L. Kasamon, Douglas E. Gladstone, William Matsui, Ivan Borrello, Carol Ann Huff, Lode J. Swinnen, Robert A. Brodsky, Richard F. Ambinder, Ephraim J. Fuchs, Gary L. Rosner, Richard J. Jones, Leo Luznik

Research output: Contribution to journalArticle

Abstract

Busulfan (Bu)/cyclophosphamide (Cy) is a standard conditioning platform for allogeneic transplantation. We developed a strategy separating the Cy into two pre/post-transplantation doses (PTCy), proviDing myeloablative conditioning and single-agent graft-versus-host disease (GVHD) prophylaxis. We investigated the impact of Bu route on treatment-related toxicity for 131 consecutive adult patients. Busulfan was administered in four daily divided doses either orally (n = 72) or intravenously (n = 59) with pharmacokinetics on the first-dose and as necessary on subsequent doses to achieve a target area-under-the-concentration-curve (AUC) of 800-1400 mol∗min/L per dose. BuCy/PTCy with pharmacokinetics is well-tolerated with low treatment-related toxicity. Hepatic veno-occlusive disease incidence was 6% with two fatal events. Bu administration route in the context of BuCy/PTCy did not statistically impact hepatotoxicity, GVHD, relapse, disease-free survival, or overall survival. The BuCy/PTCy platform has a low incidence of treatment-related toxicity, incluDing hepatotoxicity, in hematologic malignancies when using pharmacokinetics for a target AUC of 800-1400 mol∗min/L, irrespective of Bu administration route.

Original languageEnglish (US)
Pages (from-to)666-675
Number of pages10
JournalLeukemia and Lymphoma
Volume57
Issue number3
DOIs
StatePublished - Mar 3 2016

Keywords

  • Busulfan
  • Posttransplantation cyclophosphamide
  • Route
  • Toxicity

ASJC Scopus subject areas

  • Hematology
  • Oncology
  • Cancer Research

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