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| Conditioning Regimens |
| Target dose adjustment of busulfan in pediatric patients undergoing bone marrow transplantation |
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| A M Bolinger1, A B Zangwill1, J T Slattery2,3, L J Risler3, D H Sultan3, D V Glidden4, D Norstad5 and M J Cowan6 |
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1University of California at San Francisco, Department of Clinical Pharmacy, San Francisco, CA, USA
2Department of Pharmaceutics, University of Washington, Seattle, WA, USA
3Fred Hutchinson Cancer Research Center, Seattle, WA, USA
4University of California at San Francisco, Department of Epidemiology and Biostatistics, San Francisco, CA, USA
5University of California at San Francisco, Department of Nursing, San Francisco, CA, USA
6University of California, Department of Pediatrics, San Francisco, CA, USA
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Correspondence to: Dr A M Bolinger, University of California at San Francisco, School of Pharmacy, Department of Clinical Pharmacy, 521 Parnassus, Room C-152, Box 0622, San Francisco, CA 94143-0622, USA
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| 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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| Keywords |
| busulfan; children; bone marrow transplantation; pharmacokinetics; toxicity |
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| Received 12 February 2001; accepted 7 September 2001 |
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| December (1) 2001, Volume 28, Number 11, Pages 1013-1018 |
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