title: Therapeutic drug monitoring is essential for intravenous busulfan therapy in pediatric hematopoietic stem cell recipients.
abstract: Busulfan is widely used for myeloablative conditioning in HSCT. Intravenous busulfan has been introduced to reduce interindividual variability in plasma levels especially in pediatric patients. TDM of intravenous busulfan was performed in 34 pediatric HSCT patients with malignant (n = 9) and non-malignant (n = 25) diseases (50% of patients <three yr) in a single-center analysis (2006-2009). Intravenous busulfan was administered twice daily in a four-h infusion according to recommended weight-based doses. Busulfan drug levels were measured, and pharmacokinetic analysis was performed. The targeted busulfan exposure was aimed to range between AUC of 9000-12, 000 ng/mL/h. In 23/34 patients (68%), the busulfan dose had to be adjusted at least once. In 16/23 patients (70%), the dose had to be increased in a range of 7 to 33%, while in 7/23 patients (30%), the dose had to be decreased by 7-20%. The need of dose adjustment was not related to weight, age, or underlying disease. Seven out of 34 patients (21%) <20 months experienced VOD despite that their total AUCs were within the target AUC. TDM of intravenous busulfan is essential to increase the efficacy and safety of busulfan-based conditioning protocols in pediatric HSCT recipients.
authors: Pediatric BMT Center, Zürich University Hospital for Children, Zürich, Switzerland.
authors: Reta
authors: R
authors: Malär
authors: Fredrik
authors: F
authors: Sjöö
authors: Katharina
authors: K
authors: Rentsch
authors: Moustapha
authors: M
authors: Hassan
authors: Tayfun
authors: T
authors: Güngör
mesh_terms: D000293:Adolescent; D000328:Adult; D019540:Area Under Curve; D002066:Busulfan / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000627:therapeutic use; D002648:Child; D002675:Child, Preschool; D016903:Drug Monitoring / Q000379:methods*; D005260:Female; D018380:Hematopoietic Stem Cell Transplantation / Q000379:methods*; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use; D007262:Infusions, Intravenous; D008297:Male; D016896:Treatment Outcome
chemical_list: D007166:Immunosuppressive Agents; D002066:Busulfan