• Gérard Michel, Dominique Valteau-Couanet, Jean-Claude Gentet, Hélène Esperou, Gérard Socié, Françoise Méchinaud, François Doz, Bénédicte Neven, Yves Bertrand, Claire Galambrun, François Demeocq, Karima Yakouben, Pierre Bordigoni, Didier Frappaz, Laurent Nguyen, and Gilles Vassal.
• Pediatric Hematology, Hopital Enfants Timone, Marseille, France.
• Pediatr Blood Cancer. 2012 Jan 1; 58 (1): 90-7.

BackgroundA prospective clinical trial was performed in order to validate the pharmacokinetic (PK) and clinical benefits of a new dosing schedule of intravenous busulfan (IV Bu) in children.ProcedureIV Bu was administered as a 2-hr infusion every 6 hr for 4 days. Five dose levels were given according to body-weight strata.ResultsThe 67 children aged from 4 months to 17.2 years were followed up over 50 months after autologous or allogeneic stem-cell transplantation. Reduced PK variability was seen after IV Bu administration enabling efficient targeting with 78% of patients within the 900-1,500 µM · min therapeutic window and reproducible exposures across administrations. No neurological complications occurred. The low incidence of hepatic veno-occlusive disease (VOD) recorded was not correlated with high area under the curve (AUC). Only stomatitis was correlated with high AUC in the autologous group. The 4-year overall survival was 59% in the autologous group and 82% in the allogeneic group.ConclusionThe new dosing schedule using IV Bu provides adequate therapeutic targeting from the first administration, with low toxicity and good disease control in high-risk children. The choice of this formulation of Bu should be considered because of its low morbidity and good outcome.Copyright © 2011 Wiley Periodicals, Inc.

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