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Intravenous Busulfan

In the Conditioning Treatment of Pediatric Patients Prior to Hematopoietic Stem Cell Transplantation

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Abstract

  • ▲ An intravenous formulation of busulfan, a cytotoxic bifunctional alkylating agent, has been developed to replace oral busulfan as a conditioning treatment prior to hematopoietic stem cell transplantation (HSCT) in pediatric patients.

  • ▲ Doses of intravenous busulfan based on actual body weight, but not age, reduce inter- and intraindividual variability in exposure.

  • ▲ In a study of intravenous busulfan as a conditioning treatment prior to allogeneic or autologous HSCT, the majority of pediatric patients, who received one of five bodyweight-based doses, achieved busulfan area under the plasma concentration-time curve (AUC) values within the targeted therapeutic range.

  • ▲ Although mean busulfan clearance values were highly variable between bodyweight strata, exposure was not affected, with no significant differences between bodyweight groups in mean AUC values.

  • ▲ The achievement of therapeutic AUC values with intravenous busulfan resulted in a high rate of sustained engraftment, low transplant-related mortality, and promising survival outcomes post-transplant.

  • ▲ Intravenous busulfan was considered to be well tolerated, in the particular context of HSCT, and no failure of HSCT due to organ toxicity was reported. Nonhematologic adverse events commonly associated with busulfan conditioning regimens were frequent, but generally of mild to moderate severity.

  • ▲ The intravenous busulfan regimen was frequently associated with elevated liver enzymes, but hepatic veno-occlusive disease (HVOD) was infrequent, of mild to moderate severity, and resolved within 10 days of diagnosis. Unlike oral busulfan, intravenous busulfan does not appear to be associated with severe HVOD or death due to organ toxicity.

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Notes

  1. The use of trade names is for product identification purposes only and does not imply endorsement.

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Acknowledgements

The manuscript was reviewed by: G. Hempel, Institut fuer Pharmazeutische und Medizinische Chemie - Klinische Pharmazie, Münster, Germany; M. Hassan, Experimental Cancer Medicine, KFC Novum, Karolinska University Hospital Huddinge, Stockholm, Sweden; G. Vassal, Institute Gustave Roussy, Villejuif, France. During the peer review process, the manufacturer of the agent under review was also offered an opportunity to comment on this article. Changes based on any comments received were made on the basis of scientific and editorial merit.

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Authors and Affiliations

  1. Wolters Kluwer Health / Adis, 41 Centorian Drive, Private Bag 65901, Mairangi Bay, North Shore 0754, Auckland, New Zealand

    Sheridan M. Hoy & Katherine A. Lyseng-Williamson

  2. Wolters Kluwer Health, Conshohocken, Pennsylvania, USA

    Sheridan M. Hoy & Katherine A. Lyseng-Williamson

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  1. Sheridan M. Hoy
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Correspondence to Sheridan M. Hoy.

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Hoy, S.M., Lyseng-Williamson, K.A. Intravenous Busulfan. Pediatr-Drugs 9, 271–278 (2007). https://doi.org/10.2165/00148581-200709040-00008

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