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