Volume – 96 , Issue-4 , Page Number – 488-496, Published date – 15/10/2025
Affiliations
Department of Hematology and Oncology, Children’s Hospital of Capital Institute of Pediatrics, No.2, Yabao Road, Chaoyang District, Beijing,100020, China.
Correspondence
Dr. Jun-hui Li, Department of Hematology and Oncology, Children’s Hospital of Capital Institute of Pediatrics, No.2, Yabao Road, Chaoyang District, Beijing,100020, China. E-mail: stonelj@126.com. Dr. Rong Liu, Department of Hematology and Oncology, Children’s Hospital of Capital Institute of Pediatrics, No.2, Yabao Road, Chaoyang District, Beijing,100020, China. E-mail: liurong201305@sina.com.
Abstract
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 Cmax 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 Capital Center for Children’s Health, Capital Medical University 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) doses were adjusted to achieve an area under the concentration versus time curve (AUC0-6) 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%. Complete donor chimerism on day 21 for T lymphocyte, grade 2-4 aGVHD, and nonrelapse mortality (NRM) incidences were 97%, 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%.
Keywords
Pharmacokinetics, AUC0-6, Toxicity.