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Conditioning Regimens

Age-dependent pharmacokinetic profile of single daily dose i.v. busulfan in children undergoing reduced-intensity conditioning stem cell transplant

Bone Marrow Transplantation volume 44, pages 145–156 (2009)Cite this article

Abstract

We studied the pharmacokinetic (PK) profile of single daily dose i.v. BU in children who underwent reduced-intensity conditioning (RIC) transplantation. A cohort of 19 patients ⩽4 years of age (group 1) and 33 patients >4 years (group 2) was studied. Patients received a BU test dose for PK studies, followed by two treatment doses adjusted to target an area under the curve (AUC) of 4000 μM min per day. Patients in group 1 attained a lower AUC as compared to group 2 (3568 vs 4035 μM min). In group 1, 67% patients and in group 2, 84% patients achieved AUC within the targeted range. Stable donor chimerism was achieved in 56% patients in group 1 and 79% in group 2. Eight patients required a second transplantation because of graft failure. Because of the concern that a low AUC adversely affected outcomes, a second cohort of 23 patients followed a modified protocol with a targeted AUC of 5000 μM min. A higher AUC was attained (4825 μM min). Stable donor chimerism was achieved in 91% of patients. Our results show that RIC regimens using two single daily doses of i.v. BU are effective in children, but a targeted AUC of 5000 μM min is recommended.

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Acknowledgements

We thank Kimberly Thormann, Jessica Guarino, Alexis Baby, Kelly Coyne, Mary Stoelinga, Theresa Morrison and the nurses of the Ambulatory Stem Cell Unit and the Oncology Unit for skillful management of patients, and Marvin M Goldenberg for editorial review.

This work was supported by a restricted grant from ESP Pharmaceuticals Inc.

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Authors and Affiliations

  1. Department of Pediatrics, Stem Cell Transplant Program, Children's Memorial Hospital, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA

    W T Tse, R Duerst, J Schneiderman, S Chaudhury, D Jacobsohn & M Kletzel

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  1. W T Tse
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Correspondence to M Kletzel.

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None of the authors have a financial interest in ESP Pharmaceuticals Inc., whose product IV Busulfex was studied in this work.

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Tse, W., Duerst, R., Schneiderman, J. et al. Age-dependent pharmacokinetic profile of single daily dose i.v. busulfan in children undergoing reduced-intensity conditioning stem cell transplant. Bone Marrow Transplant 44, 145–156 (2009). https://doi.org/10.1038/bmt.2008.437

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