A Retrospective Analysis Of Risk Factors That Influence Intravenous Busulfan Kinetics In Adult Patients
Year: 2009
Type: article
Abstract: Busulfan (Bu) is a bifunctional alkylating agent that is a common component of conditioning regimens prior to hematopoetic stem cell transplantation (HSCT). Bu pharmacokinetics, either with area under the curve (AUC) or average concentration at steady state (Css), can be utilized to evaluate efficacy and prevent adverse effects such as hepatic veno-occlusive disease (VOD). Pharmacokinetic models that predict Bu levels were historically performed with q 6 hour oral dosing in the pediatric population and used a limited linear regression model. Since the advent of intravenous (IV) Bu, a consistent pharmacokinetic modeling system based on specific patient parameters has not emerged. Likewise, current Bu pharmacokinetics models may not be accurate in adult patients or with once-daily dosing schedules. We will report a retrospective study of approximately 300 patients and present a predictive pharmacokinetic model for appropriate AUC with once-daily IV Bu in adult patients. Our model will be based on first dose kinetic analyses. We will also evaluate currently published risk factors that may influence IV Bu kinetic parameters using univariate, multivariate and stepwise Cox regression analyses. Age, race, gender, disease state, disease status at time of transplantation, number of previous chemotherapy regimens, renal and hepatic function at time of transplant and graft source will be evaluated. Long-term outcomes to be examined include overall mortality, probability of survival, development of acute and chronic graft versus host disease (GVHD), development of VOD and days until neutrophil and platelet engraftment. Statistical model design and specific data results will be presented at the 2009 ASBMT Annual Conference.
Language: English
Subfield: Hematology
Field: Medicine
Domain: Health Sciences
Open Access status: hybrid
Estimated APC paid: $3,650
OpenAlex ID: W2083164738