BU levels are largely unpredictable, patients are often exposed to the toxic effects of
inappropriate drug regimens before dose modifications can be made. Although the importance
of TDM cannot be over emphasized, it entails trial and error and does not allow for pre-
treatment dose optimization. This study, which provides an integration of genetic and
pharmacokinetic data analysis of patients preconditioned for HSCT with high dose oral BU,
aims to define biomarkers predictive of poor BU metabolism and clearance to prevent
potential drug toxicity.This study is not an interventional study, only investigates the GST
and MDR-1 genes in correlation with the "routine" Busulfan AUC done during the preparative
regimen in HSCT for AML patients.
Time Perspective: Prospective
If GST and ABCB1 genes modify busulfan pharmacokinetics in AML patients who will be transplanted
If individuals diagnosed with AML carrying the GSTP1 variant allele rs1695 (heterozygotes) are at risk of developing supra-therapeutic BU AUC due to lower BU clearance, and if combined polymorphisms in GSTM1 and ABCB1 (3435 or 2677) are associated with BU clearance rates and AUC.
end of BMT transplantation
Israel: Ministry of Health