Impact of Intravenous Busulfan Pharmacokinetics on Safety in Pediatric Patients who have undergone Hematopoietic Stem Cell Transplant

Introduction: Busulfan (Bu)-based regimens are crucial for myeloablative conditioning in pediatric allogeneic stem cell transplantation. Despite its efficacy, Intravenous Bu has a narrow therapeutic index and variable pharmacodynamics especially in children, heightening the risk of adverse events. This study explores Bu dosing and related organ toxicities in pediatric patients at a tertiary center in Saudi Arabia. Methodology: This retrospective study at King Fahad Specialist Hospital in Dammam (KFSH-D), Saudi Arabia, included pediatric patients (≤16 years) treated with intravenous Bu before bone marrow transplantation from 2010 to 2022. Pharmacokinetic dose adjustments were based on AUC targets of 900-1350 µMol-min. Descriptive measures included mean, Standard Deviation (SD), median, minimum-maximum values, counts, and percentages. Statistical analyses used Kruskal-Wallis, Chi-square, and Fisher’s exact tests. Ethical approval was obtained from KFSH-D. Results: We identified 44 pediatric patients who underwent Bu prior to HSCT. Mean age was 4.95 ± 2.49 years, with a female majority (56.8%). Primary diseases included Beta Thalassemia (34.09%), Neuroblastoma (29.55%) among others. There was no significant difference in the cohort’s demographic and clinical features of the cohort. Nonetheless, higher infections were found in the Low-AUC group (66.7%) compared to the Target-AUC (40.0%) and Higher-AUC groups (0.0%) (p = 0.015). Conclusion: This study emphasizes the need for therapeutic drug monitoring and individualized Bu dosing in pediatric HSCT to minimize toxicity and improve outcomes. Larger multicenter studies are recommended to refine dosing strategies and enhance the safety and efficacy of Bu-based regimens.