Intravenous busulfan for allogeneic hematopoietic stem cell transplantation in infants: clinical and pharmacokinetic results

Bone Marrow Transplant. 2003 Oct;32(7):647-51. doi: 10.1038/sj.bmt.1704209.

Abstract

High-dose busulfan is an important component of myeloablative regimens. Variable drug exposure may occur following oral administration. Therefore, the use of intravenous busulfan has been advocated. Previous work has suggested a cumulative dosage of 16 mg/kg for haematopoietic transplantation in children less than 3 years of age, but only limited data are available in infants. Pharmacokinetics of intravenous busulfan administered at the suggested dosage were studied in 14 infants (median age 4.7 months). Busulfan plasma concentrations were measured by either GC-MS or HPLC-UV. In seven patients, the dose was decreased to target an area- under- the- curve of 600-1300 micromol min. The median total dose given was 13.8 mg/kg. All patients engrafted. Severe veno-occlusive disease occurred in one patient. Our study demonstrates that a cumulative dosage of 16 mg/kg is associated with higher exposure than expected in infants. We suggest an initial dose of 0.8 mg/kg followed by pharmacokinetically guided dose adjustment.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Area Under Curve
  • Busulfan / administration & dosage*
  • Busulfan / blood
  • Busulfan / pharmacokinetics
  • Chromatography, High Pressure Liquid
  • Drug Evaluation
  • Drug Monitoring
  • Female
  • Gas Chromatography-Mass Spectrometry
  • Graft Survival
  • Hematopoietic Stem Cell Transplantation / adverse effects
  • Hematopoietic Stem Cell Transplantation / methods*
  • Hematopoietic Stem Cell Transplantation / mortality
  • Hepatic Veno-Occlusive Disease / chemically induced
  • Humans
  • Infant
  • Injections, Intravenous
  • Male
  • Pharmacokinetics
  • Retrospective Studies
  • Transplantation Conditioning / adverse effects
  • Transplantation Conditioning / methods
  • Transplantation, Homologous

Substances

  • Busulfan