Simplifying Busulfan Conditioning in Children: Once Daily vs. Four-Times-Daily IV Dosing in Hematopoietic Cell Transplantation

Background/Objectives: Busulfan is a key component of conditioning regimens for hematopoietic cell transplantation (HCT). Although once-daily (OD) intravenous administration is logistically advantageous over the conventional four-times-daily (QID) schedule, concerns remain regarding a potential increased risk of hepatic veno-occlusive disease (VOD or sinusoidal obstruction syndrome/SOS), particularly in children. Methods: We retrospectively reviewed all pediatric patients receiving busulfan-based conditioning with therapeutic drug monitoring (TDM) at a single center (January 2015–December 2024). The primary analysis compared VOD/SOS incidence within 100 days post-HCT, diagnosed by revised EBMT criteria, between the OD and allogeneic QID groups (QIDallo). Secondary analyses evaluated VOD/SOS severity, busulfan pharmacokinetic (PK) parameters, and clinical risk factors and compared the OD and total QID groups. Results: One hundred HCT procedures were included (36 OD, 64 QIDtot including 39 QIDallo). There was no statistically significant between-group difference (p = 0.777 for OD/QIDallo and p = 0.960 for OD/QIDtot), including after adjustment for age and disease. OD yielded higher Cmax than QIDallo and QID (p < 0.001), but PK parameters were not associated with VOD/SOS. Independent risk factors were age ≤5 years (p = 0.001) and thalassemia (p = 0.035). Conclusions: In this pediatric cohort, PK-guided OD busulfan was not associated with an increased VOD/SOS risk despite higher Cmax, supporting its use in children when TDM is implemented. Young age and thalassemia remained the principal determinants of VOD/SOS.