Precision dosing of intravenous busulfan in infants patients undergoing bone marrow transplantation in China

Veno-occlusive disease (VOD) is a severe adverse reaction to busulfan-containing regimens used in the preparation of children for hematopoietic stem cell transplantation (HSCT). We previously found that the youngest children have a greater risk of VOD, and a high busulfan C _max is more likely to occur after the first two doses. We conducted a retrospective pharmacokinetic analysis of IV (intravenous) busulfan in infants undergoing a hematopoietic stem cell transplantation (HSCT) and described its relation to transplantation outcomes. Thirty-four infants (median age, 8.5 months) underwent HSCT at The Hospital of Capital Institute of Pediatrics from October 2018 through April 2024 and received IV busulfan every 6 hour (h) as part of their conditioning regimen. Initial busulfan doses were based on actual patient weight: <9 kg, 0.75–1.1 mg/kg per dose (mean dose 0.91 mg/kg, mean 13.45 doses, mean total dosage 12.35 mg/kg ); 9–12 kg, 0.82–1.2 mg/kg per dose (mean dose 0.96 mg/kg, mean 13 doses, mean total dosage 12.84 mg/kg). Plasma busulfan concentrations were obtained after the first or fifth dose. The fourth or the eighth and subsequent busulfan (Bu/BSF) doses were adjusted to achieve an area under the concentration versus time curve (AUC) of 1125 µmol*min/L ± 10% depending on donor source and disease. After the first dose, median AUC was 758.2 (530.02-1335.9) µmol*min/L. Thirteen infants had Bu IV dose decreased by > 10%. Neutrophil and platelet recoveries, grade 2–4 aGVHD, and nonrelapse mortality (NRM) incidences were 97%, 94%, 11.7%, and 2.9%, respectively. Relapse incidence was 5.9%. Incidence of veno-occlusive disease, hemorrhagic cystitis, and lung toxicities were 9%, 3%, and 6%, respectively. OS and EFS were 91% and 91%.