Favorable Outcome of Hematopoietic Stem Cell Transplantation Using a Targeted Once-Daily Intravenous Busulfan–Fludarabine–Etoposide Regimen in Pediatric and Infant Acute Lymphoblastic Leukemia Patients

• Targeted once-daily IV BuFluVP regimen showed favorable outcome in pediatric ALL.
• Treatment outcome in infant ALL was also promising with tolerable toxicity.
• Once-daily IV BuFluVP regimen could be one option in pediatric and infant ALL.
• Daily TDM and dose adjustment were used in this study.

Conditioning regimens for pediatric acute lymphoblastic leukemia (ALL) usually include total body irradiation (TBI), but TBI may result in serious sequelae. Busulfan and cyclophosphamide have been used as an alternative to TBI. Etoposide also has been widely used to enhance antileukemic effect. However, toxicities have been reported in some studies using busulfan, cyclophosphamide, and etoposide regimen. A reduced toxicity myeloablative regimen using busulfan and fludarabine showed promising results. Also, therapeutic drug monitoring (TDM) and administration of targeted doses of busulfan have been recommended to improve the outcome of hematopoietic stem cell transplantation (HSCT). In this study, we evaluated the outcome of HSCT using a targeted once-daily i.v. busulfan–fludarabine–etoposide (BuFluVP) regimen in pediatric and infant ALL. Busulfan (age ≥ 1 year, 120 mg/m2; age < 1 year, 80 mg/m2) was administered once daily as the first dose on day −8, and a targeted dose of busulfan was used according to the TDM results on days −7 to −5. Forty-four patients were evaluated. Donor-type neutrophil engraftment was achieved in all patients. Veno-occlusive disease occurred in 7 patients (15.9%), but all patients were successfully treated. Cumulative incidence of treatment-related mortality and relapse were 9.1% and 9.9%, respectively. One-year overall survival and event-free survival rates of all patients were 86.2% and 83.8%, respectively. Twelve patients (27.3%) were infants at diagnosis, and their 1-year overall survival rate was 83.3%. Our study demonstrated that HSCT using a targeted once-daily i.v. BuFluVP regimen showed favorable outcomes and could be an option for HSCT in pediatric and infant ALL.