Modification of the Bu/Cy myeloablative regimen using daily parenteral busulfan: reduced toxicity without the need for pharmacokinetic monitoring.
Pharmacokinetic and clinical outcome measures among three groups of patients undergoing hematopoietic transplant were assessed: group A: Parenteral busulfan (Bu) 3.2 mg/kg i.v. given qd, n=20; group B: parenteral Bu 0.8 mg/kg i.v. given every 6 h, n=11; group C: Bu 1 mg/kg p.o. given every 6 h, n=25. All groups received Bu over 4 days followed by Cy 60 mg/kg i.v. qd over 2 days; followed by an infusion of allogeneic stem cells. Median Bu clearance was 3.21 ml/min/kg and median daily AUC was 4071 micromol/min for the group A patients. The dosing formula for Bu i.v. qd was highly predictive of the AUC for patients whose mass < or =IBW+20%. For patients of greater mass, the dosing formula uniformly resulted in lower-than-predicted AUC. Neurologic toxicity, hepatic toxicity, hematologic engraftment, and relapse at 100 days were comparable across all three groups. Severe AGVHD was least among group A, followed by group B when compared with group C. Bu i.v. qd is a safe and effective regimen for allogeneic transplantation and is at least clinically equivalent to every 6 h dosing schemes using either oral or parenteral Bu.