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

Abstract

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/m(2); age < 1 year, 80 mg/m(2)) 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.

Factors Associated with Long-Term Risk of Relapse after Unrelated Cord Blood Transplantation in Children with Acute Lymphoblastic Leukemia in Remission

“…Concerns regarding the considerable late effects associated with TBI 48 , including neurocognitive effects 49–51 , have led to the practice of using chemotherapy-based regimens in young children. Older children and adolescents routinely receive TBI as part of conditioning, although TBI-sparing strategies in this population continue to be explored 52–54 . Our results, after adjusting for age and other clinical factors, support the use of TBI as a critical component of treatment.…”

Pediatric patients undergoing hematopoietic stem cell transplantation can greatly benefit from a novel once‐daily intravenous busulfan dosing nomogram

“…The busulfan dose on day 4 was the median total target AUC (i.e., 75 mg·h/L) less the cumulative AUC over the previous 3 days, multiplied by the estimated CL on day 3 . The target AUCs were set as proposed in the literature, which showed favorable outcomes in pediatric and infant patients . This study was approved by the Institutional Review Board of Seoul National University Hospital (H‐ 1310‐121‐532).…”

Favorable Outcome of Post-Transplantation Cyclophosphamide Haploidentical Peripheral Blood Stem Cell Transplantation with Targeted Busulfan-Based Myeloablative Conditioning Using Intensive Pharmacokinetic Monitoring in Pediatric Patients

“…In the present study, we used an intensive daily pharmacokinetic (PK) monitoring method for busulfan dosing and optimized the intensity of the conditioning regimen by calculating the total exposure of busulfan [33][34][35][36]. Here, we applied this targeted-busulfan method using the daily PK monitoring of haplo-HSCT using PTCy in pediatric patients, and the safety and outcomes were evaluated.…”