Therapeutic drug monitoring-guided dosing of busulfan differs from weight-based dosing in hematopoietic stem cell transplant patients

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Abstract

Busulfan (Bu)-based preparative regimens in hematopoietic stem cell transplantation are commonly used. Previous studies have shown that Bu at a fixed dose of 3.2 mg/kg/day (FBD) given intravenously decreases variability in drug pharmacokinetics and this decreases the dependency on therapeutic drug monitoring (TDM) of Bu. We compared the Bu dose given using TDM with the FBD of 3.2 mg/kg/day. Seventy-three patients with acute leukemia, myelodysplasia, chronic myeloid leukemia, thalassemia major, and sickle cell disease were included. The mean age at transplant was 15 years (range 2–55 years) with 57% adults. Indication for transplantation was leukemia/myelodysplastic syndrome in 46% of the patients, while the remaining 54% were transplanted for inherited blood disorders. We found that the median FBD was lower than the median TDM dose by 39 mg/day with a statistically significant difference (p < 0.001) even after adjusting for the weight (median total FBD of 349 mg, median TDM dose of 494 mg, p < 0.0001). Age and underlying condition (malignant vs. nonmalignant) were the main factors affecting Bu clearance (p < 0.001 and p < 0.07, respectively). TDM remains an important tool for the appropriate dosing of Bu in preparative regimens of hematopoietic stem cell transplantation, especially in populations with genetic admixture.

Original languageEnglish
Pages (from-to)70-78
Number of pages9
JournalHematology/ Oncology and Stem Cell Therapy
Volume10
Issue number2
DOIs
Publication statusPublished - Jun 1 2017

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Keywords

  • Busulfan
  • Drug monitoring
  • Hematopoietic stem cell transplantation
  • Pharmacokinetics

ASJC Scopus subject areas

  • Hematology
  • Oncology

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