Intravenous Busulfan in Hematopoietic Stem Cell Transplantation:

Purpose The objective of this study is to ascertain factors that may be significantly associated with busulfan clearance (patient demographics (age, gender, race, weight), disease and donor type). Methods This retrospective study was conducted to determine population descriptive statistics (i.e. mean clearance, mean AUC, mean half-life, etc.). Additionally, the effect of independent variables age, gender, primary cancer diagnosis, ethnicity, prior transplant status, and transplant type were analyzed for effect on the dependent variable of normalized clearance. Institutional Review Board approvals were obtained as required for this retrospective data review. Patients included in this study were treated between September 2009 and December 31, 2012. Regression analysis was performed on patient specific variables (i.e. age, gender, disease) to determine which variables may significantly affect clearance. The association of patient factors with busulfan clearance was tested using linear regression. In this analysis, busulfan clearance is the dependent variable and is continuously distributed. Results 752 patients were included in this analysis. Patients had a mean age of 46.2 years and a mean clearance of 101.2 ml/min/m2, with a standard deviation of 17.5 and a range of 51.5 to 150 ml/min/m2. With univariate analysis, only diagnosis (p <0.0001) and transplant type (p=0.0002) were statistically significant variables. Including all 6 variables produced a significant model (p-value < 0.0001) with an R2 = 0.0667. Conclusion The complete six variable model only explains 6.7% of the variability in patient specific busulfan clearance. Given the large variability between patients, this is not a good model for predicting variation in clearances based on patient factors.