Weight-based strategy of dose administration in children using intravenous busulfan: clinical and pharmacokinetic results

Pediatr Blood Cancer. 2012 Jan;58(1):90-7. doi: 10.1002/pbc.22959. Epub 2011 Jan 19.


Background: A prospective clinical trial was performed in order to validate the pharmacokinetic (PK) and clinical benefits of a new dosing schedule of intravenous busulfan (IV Bu) in children.

Procedure: IV Bu was administered as a 2-hr infusion every 6 hr for 4 days. Five dose levels were given according to body-weight strata.

Results: The 67 children aged from 4 months to 17.2 years were followed up over 50 months after autologous or allogeneic stem-cell transplantation. Reduced PK variability was seen after IV Bu administration enabling efficient targeting with 78% of patients within the 900-1,500 µM · min therapeutic window and reproducible exposures across administrations. No neurological complications occurred. The low incidence of hepatic veno-occlusive disease (VOD) recorded was not correlated with high area under the curve (AUC). Only stomatitis was correlated with high AUC in the autologous group. The 4-year overall survival was 59% in the autologous group and 82% in the allogeneic group.

Conclusion: The new dosing schedule using IV Bu provides adequate therapeutic targeting from the first administration, with low toxicity and good disease control in high-risk children. The choice of this formulation of Bu should be considered because of its low morbidity and good outcome.

MeSH terms

  • Adolescent
  • Antineoplastic Agents, Alkylating / administration & dosage
  • Antineoplastic Agents, Alkylating / pharmacokinetics
  • Area Under Curve
  • Body Weight*
  • Busulfan / administration & dosage*
  • Busulfan / pharmacokinetics*
  • Child
  • Child, Preschool
  • Combined Modality Therapy
  • Female
  • Follow-Up Studies
  • Hematologic Neoplasms / therapy*
  • Hematopoietic Stem Cell Transplantation*
  • Hepatic Veno-Occlusive Disease / prevention & control
  • Humans
  • Infant
  • Injections, Intravenous
  • Male
  • Prognosis
  • Survival Rate
  • Tissue Distribution
  • Transplantation, Homologous


  • Antineoplastic Agents, Alkylating
  • Busulfan