Retrospective appraisal of busulfan dose adjustment in children

This report describes and critically appraises our experience with busulfan dose adjustment in children undergoing bone marrow transplant between April 1997 and March 1999. All children received an initial busulfan dose of 40 mg/m(2) p.o. or by nasogastric tube, Whole blood samples were obtained 1, 1.5 and 6 h later and analyzed for busulfan content by gas chromatography with electron capture detection. The area under the whole blood busulfan concentration vs time curve (AUC) and an individualized dose which would achieve an AUC of 1300 muM/min were calculated. Mean and median busulfan doses were calculated using actual, ideal and effective body weight and stratified according to age. The relationship between the busulfan concentration at hour 6 and AUC was determined using linear regression. Thirty-nine courses of busulfan were evaluated in 38 patients. A change from the initial busulfan dose was required to achieve the target AUC in 34 courses (87%). Most children >1 to 5 years old required dose increments while most children >5 years old required dose reductions, Obesity did not significantly affect busulfan dose requirements, Busulfan concentrations at 6 h only weakly predicted the AUC achieved (r(2) = 0.496; P = 0.001). Based on these findings, we recommend that the initial busulfan dose be assigned according to patient age and actual body weight. We also recommend that busulfan AUC be calculated for children using a four-sample (1, 1.5, 4 and 6 h) limited sampling technique.