Age-dependent pharmacokinetic profile of single daily dose i.v. busulfan in children undergoing reduced-intensity conditioning stem cell transplant

We studied the pharmacokinetic (PK) pro. le of single daily dose i.v. BU in children who underwent reduced-intensity conditioning (RIC) transplantation. A cohort of 19 patients <= 4 years of age (group 1) and 33 patients 44 years (group 2) was studied. Patients received a BU test dose for PK studies, followed by two treatment doses adjusted to target an area under the curve (AUC) of 4000 mu M min per day. Patients in group 1 attained a lower AUC as compared to group 2 (3568 vs 4035 mu M min). In group 1, 67% patients and in group 2, 84% patients achieved AUC within the targeted range. Stable donor chimerism was achieved in 56% patients in group 1 and 79% in group 2. Eight patients required a second transplantation because of graft failure. Because of the concern that a low AUC adversely affected outcomes, a second cohort of 23 patients followed a modified protocol with a targeted AUC of 5000 mu M min. A higher AUC was attained (4825 mu M min). Stable donor chimerism was achieved in 91% of patients. Our results show that RIC regimens using two single daily doses of i.v. BU are effective in children, but a targeted AUC of 5000 mu M min is recommended. Bone Marrow Transplantation ( 2009) 44, 145-156; doi: 10.1038/bmt.2008.437; published online 2 February 2009