• Donna A Wall, Ka Wah Chan, Michael L Nieder, Robert J Hayashi, Andrew M Yeager, Richard Kadota, Donna Przepiorka, Khaled Mezzi, Morris Kletzel, and Pediatric Blood, Marrow Transplant Consortium.
• Cardinal Glennon Children's Hospital/Saint Louis University, St. Louis, Missouri, USA. donna.wall@cancercare.mb.ca
• Pediatr Blood Cancer. 2010 Feb 1;54(2):291-8.

PurposeTo 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).MethodsTwenty-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 microMol-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.ResultsThe 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 < or =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.ConclusionIVBu is a safe and effective and offers the benefit of predictable and consistent systemic exposure.(c) 2009 Wiley-Liss, Inc.

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