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Conditioning Regimens

An evaluation of engraftment, toxicity and busulfan concentration in children receiving bone marrow transplantation for leukemia or genetic disease

Bone Marrow Transplantation volume 25, pages 925–930 (2000)Cite this article

Abstract

Autologous recovery is a major problem with busulfan as a marrow ablative agent in conditioning children for allogeneic BMT. Data suggest the average concentration of busulfan at steady state (Bu Css) is critical for successful engraftment. We prospectively evaluated busulfan pharmacokinetics in 31 children (age 0.6–18 years) with AML (n = 9), and non-malignant diseases (n = 22) receiving HLA-closely matched (sibling, parent, unrelated) donor grafts. Blood samples were obtained following dose 1 and 13 of a standard 16 dose, 4-day regimen. The busulfan dose varied from 14 to 20 mg/kg. Patients received cyclophosphamide 200–240 mg/kg; 22/31 received 80–90 mg/kg of ATG. Eight patients failed to engraft (26%). ATG did not appear to influence engraftment (P = 0.38). Bu Css levels <600 ng/ml correlated with autologous recovery/mixed chimerism (P = 0.018). there were no graft failures in patients with a bu css >600 ng/ml. a correlation between bu css levels and regimen-related toxicity (rrt) was not identified for grade 2 or higher toxicities, only 1/31 had a bu css >900 ng/ml. Our data support the use of pharmacokinetic monitoring of busulfan. Bone Marrow Transplantation (2000) 25, 925–930.

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Acknowledgements

This work was supported in part by NIH grant M01-RR01271, Pediatric Clinical Research Center; NIH grant CA18029, Children’s Cancer Research Fund of the University of Minnesota.

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Authors and Affiliations

  1. Department of Clinical Pharmacy, University of California at San Francisco, USA

    AM Bolinger & AB Zangwill

  2. Department of Pharmaceutics, University of Washington, USA

    JT Slattery

  3. Fred Hutchinson Cancer Research Center, USA

    JT Slattery & LJ Risler

  4. Department of Epidemiology and Biostatistics, University of California at San Francisco, USA

    D Glidden

  5. Department of Pediatrics, University of Wisconsin, USA

    K DeSantes

  6. Department of Nursing, University of California at San Francisco, USA

    L Heyn

  7. Department of Pediatrics, University of Minnesota, USA

    B Bostrom

  8. Department of Pediatrics, University of California at San Francisco, San Francisco, CA, USA

    MJ Cowan

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  1. AM Bolinger
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Bolinger, A., Zangwill, A., Slattery, J. et al. An evaluation of engraftment, toxicity and busulfan concentration in children receiving bone marrow transplantation for leukemia or genetic disease. Bone Marrow Transplant 25, 925–930 (2000). https://doi.org/10.1038/sj.bmt.1702371

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