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Conditioning Regimens

Target dose adjustment of busulfan in pediatric patients undergoing bone marrow transplantation

Bone Marrow Transplantation volume 28, pages 1013–1018 (2001)Cite this article

Abstract

Published data suggest that the average concentration of busulfan at steady state (Bu Css) is critical for successful engraftment in children receiving busulfan as a conditioning agent for bone marrow transplantation (BMT). We previously found in children that a Bu Css <600 ng/ml correlated with autologous recovery/mixed chimerism; there was no correlation between Bu Css and regimen-related toxicity (RRT). In a cohort continuous with the previous trial, we prospectively evaluated targeted busulfan concentrations in 32 pediatric patients (age 0.6–18.5 years) with AML (n = 6), CML (n = 6) and non-malignant disorders (n = 20) receiving HLA-closely matched donor grafts. In this trial, individual busulfan pharmacokinetics were performed prior to admission. Busulfan doses were then adjusted to achieve a Bu Css target range of 600–900 ng/ml ± 10% depending on donor source and disease. A repeat study was done following dose 1 of the conditioning regimen. Thirty of thirty-two (94%) patients achieved target concentrations. Total busulfan doses ranged from 10.9 to 29 mg/kg. Thirty of thirty-two patients (94%) have durably engrafted. Grade 3/4 RRT occurred in seven patients (21%). Targeting Bu Css ranges of 600–900 ng/ml significantly improved our rate of successful engraftment from 74% to 94% (P = 0.043). These results indicate that targeted busulfan dosing optimizes allogeneic engraftment in children.

Bone Marrow Transplantation (2001) 28, 1013–1018.

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References

  1. Growchow LB, Krivit W, Whitley CB, Blazer BR . Busulfan disposition in children Blood 1990 75: 1723–1727

    Google Scholar 

  2. Hassan M, Oberg G, Beckassy AN et al. Pharmacokinetics of high dose busulphan in relation and age and chronopharmacology Cancer Chemother Pharmacol 1991 28: 130–134

    Article  CAS  Google Scholar 

  3. Vassal G, Gouyette A, Hartmann O et al. Pharmacokinetics of high dose busulfan in children Cancer Chemother Pharmacol 1989 24: 386–390

    Article  CAS  Google Scholar 

  4. Vassal G, Deroussent A, Hartmann O et al. Dose-dependent neurotoxicity of high-dose busulfan in children: a clinical and pharmacological study Cancer Res 1990 50: 6203–6207

    CAS  Google Scholar 

  5. Slattery JT, Sanders JE, Buckner CD et al. Graft-rejection and toxicity following bone marrow transplantation in relation to busulfan pharmacokinetics Bone Marrow Transplant 1995 16: 31–42

    CAS  Google Scholar 

  6. Slattery JT, Clift RA, Buckner CD et al. Marrow transplantation for chronic myeloid leukemia: the influence of plasma busulfan levels on the outcome of transplantation Blood 1997 89: 3055–3060

    CAS  Google Scholar 

  7. Bolinger AM, Zangwill AB, Slattery JT et al. An evaluation of engraftment, toxicity and busulfan toxicity in children receiving bone marrow transplantation for leukemia or genetic disease Bone Marrow Transplantation 2000 25: 925–930

    Article  CAS  Google Scholar 

  8. Slattery JT, Risler LJ . Therapeutic monitoring of busulfan in hematopoietic stem cell transplantation Ther Drug Monitor 1998 20: 543–549

    Article  CAS  Google Scholar 

  9. Bearman SI, Applelbaum FR, Buckner CD et al. Regimen-related toxicity in patients undergoing bone marrow transplantation J Clin Oncol 1988 6: 562–568

    Article  Google Scholar 

  10. McCune JS, Gibbs JP, Slattery JT . Plasma concentration monitoring of busulfan: does it improve clinical outcome? Clin Pharmacokinetics 2000 39: 155–165

    Article  CAS  Google Scholar 

  11. Regazzi MB, Locatelli F, Buggia I et al. Disposition of high-dose busulfan in pediatric patients undergoing bone marrow transplantation Clin Pharmacol Ther 1993 54: 45–52

    Article  CAS  Google Scholar 

  12. Lee JL, Gooley T, Bensinger W et al. Veno-occlusive disease of the liver after busulfan, melphalan and thiotepa conditioning therapy: incidence, risk factors and outcome Biol Blood Marrow Transplant 1999 5: 306–315

    Article  CAS  Google Scholar 

  13. Demirer T, Buckner CD, Applebaum FR et al. Busulfan, cyclophosphamide and fractionated total body irradiation for autologous or syngeneic marrow transplantation for acute and chronic myelogenous leukemia: phase I dose escalation of busulfan based on targeted plasma levels Bone Marrow Transplant 1996 17: 491–495

    CAS  PubMed  Google Scholar 

  14. Chattergoon DS, Saunders EF, Klein J et al. Improved limited sampling method for individualized busulfan dosing in bone marrow transplantation in children Bone Marrow Transplant 1997 20: 347–354

    Article  CAS  Google Scholar 

  15. Growchow LB . Busulfan disposition: the role of therapeutic monitoring in bone marrow transplantation induction regimens Semin Oncol 1993 20 (Suppl. 4): 18–25

    Google Scholar 

  16. Dix SP, Wingard JR, Mullins RE et al. Association of busulfan area under the curve with veno-occlusive disease following BMT Bone Marrow Transplant 1996 17: 225–230

    CAS  Google Scholar 

Download references

Acknowledgements

This work was supported in part by NIH grant M01-RR01271, Pediatric Clinical Research Center; NIH grant CA18029.

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Authors and Affiliations

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

    AM Bolinger & AB Zangwill

  2. Department of Pharmaceutics, University of Washington, Seattle, WA, USA

    JT Slattery

  3. Fred Hutchinson Cancer Research Center, Seattle, WA, USA

    JT Slattery, LJ Risler & DH Sultan

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

    DV Glidden

  5. Department of Nursing, University of California at San Francisco, San Francisco, CA, USA

    D Norstad

  6. Department of Pediatrics, University of California, 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. Target dose adjustment of busulfan in pediatric patients undergoing bone marrow transplantation. Bone Marrow Transplant 28, 1013–1018 (2001). https://doi.org/10.1038/sj.bmt.1703264

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  • DOI: https://doi.org/10.1038/sj.bmt.1703264

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