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Safety, efficacy, and pharmacokinetics of intravenous busulfan in children undergoing allogeneic hematopoietic stem cell transplantation
Author(s) -
Wall Donna A.,
Chan Ka Wah,
Nieder Michael L.,
Hayashi Robert J.,
Yeager Andrew M.,
Kadota Richard,
Przepiorka Donna,
Mezzi Khaled,
Kletzel Morris
Publication year - 2010
Publication title -
pediatric blood and cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.116
H-Index - 105
eISSN - 1545-5017
pISSN - 1545-5009
DOI - 10.1002/pbc.22227
Subject(s) - medicine , busulfan , dosing , pharmacokinetics , hematopoietic stem cell transplantation , context (archaeology) , cyclophosphamide , transplantation , regimen , gastroenterology , area under the curve , surgery , chemotherapy , paleontology , biology
Purpose To determine the safety, efficacy, and PK profile of intravenous busulfan (Bu) in the context of a Bu and cyclophosphamide (IVBuCy) preparative regimen in children undergoing allogeneic hematopoietic stem cell transplantation (HSCT). Methods Twenty‐four children were enrolled in an open‐label, multicenter trial of IVBuCy as the preparative regimen for HLA‐matched sibling allogeneic HSCT. IVBu was administered q6 hr for 16 doses with a targeted area under the curve (AUC) of 900–1,350 µMol‐min. The initial dose was 0.8 mg/kg for children >4 years of age and 1 mg/kg for those <4 years of age. PK of the first dose IVBu was determined to calculate a single dosage adjustment, and with the 9th and 13th doses to confirm steady‐state PK. Results The targeted AUC was achieved with the first dose in 17/24 (71%) of the children using the age‐adjusted dosing approach. Dosing was increased in five patients, and reduced in two patients to achieve target values. After dose adjustment based on PK, 91% of the children had an AUC within the target range at steady state (AUCss). Median final dosing and clearance (CL) of IVBu were 1.1 mg/kg and 4.1 ml/min/kg in patients ≤4 years, and 0.9 mg/kg and 2.9 ml/min/kg in patients >4 years. All children were engrafted with documented donor chimerism. No late rejections or graft failures occurred. Four patients had veno‐occlusive disease, three of which resolved within 2 weeks of onset. Two children died from transplant‐related causes unrelated to Bu. Conclusion IVBu is a safe and effective and offers the benefit of predictable and consistent systemic exposure. Pediatr Blood Cancer 2010;54:291–298. © 2009 Wiley‐Liss, Inc.