Once-daily intravenous busulfan with therapeutic drug monitoring compared to conventional oral busulfan improves survival and engraftment in children undergoing allogeneic stem cell transplantation

I.H. Bartelink, R.G. Bredius, F.F.T. Ververs, M.F. Raphael, Charlotte van Kesteren, M.B. Bierings, C.M.A. Rademaker, J. den Hartigh, C.S.P.M. Uiterwaal, J. Zwaveling, J.J. Boelens

Research output: Contribution to journalArticleAcademicpeer-review

Abstract

Because of intra- and interindividual variability, bioavailability, and pharmacokinetics of busulfan (Bu) in children, oral busulfan without therapeutic drug monitoring (TDM) is assumed to be associated with higher graft failure rates as well as higher toxicity (eg, veno-occlusive disease [VOD]). This study compares the outcome of hematopoietic stem cell transplantation (HSCT) of 2 groups: 1) 30 patients who received myeloablation with once-daily intravenous (i.v.) dose-targeted busulfan (BUdtIV) based on TDM and 2) 30 patients who received the current practice of untargeted oral busulfan (BLTPO). Patients received a 3-hour infusion of Bu at a first dose of 120 mg/m(2) (age >= 1 year) or 80 mg/m(2) (<1 year), or BUPO 1 mg/kg 4 times daily. Both regimens were continued for 4 days. The target area under the curve (AUC) was defined as 17,500 mu g*h/1. BUdtIV resulted in higher event-free survival (EFS) and survival rates compared to BUPO (EFS: 30% versus 83 %, P

Original languageEnglish
Pages (from-to)88-98
Number of pages11
JournalBiology of Blood and Marrow Transplantation
Volume14
Issue number1
DOIs
Publication statusPublished - Jan 2008

Keywords

  • busulfan
  • allogeneic stem cell transplantation
  • therapeutic drug monitoring
  • BONE-MARROW-TRANSPLANTATION
  • ADVANCED HEMATOLOGIC MALIGNANCIES
  • VENO-OCCLUSIVE DISEASE
  • HEMOPHAGOCYTIC LYMPHOHISTIOCYTOSIS
  • VENOOCCLUSIVE DISEASE
  • CONDITIONING THERAPY
  • DOSE ADJUSTMENT
  • PEDIATRIC-PATIENTS
  • COMPLETE REMISSION
  • MYELOID-LEUKEMIA

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