Abstract
To evaluate the toxicity and efficacy of an i.v. preparation of BU (12.8 mg/kg), combined with CY (120 mg/kg), a prospective study was performed on 30 Japanese patients (median age, 30 years) with hematologic malignancies undergoing hematopoietic SCT (28 allogeneic transplants from an HLA-matched donor and 2 autologous transplants). There were no significant toxicities, and all but one patient showed evidence of granulocyte engraftment at a median of 14 days for allogeneic and 11 days for autologous transplantation. Grades II–IV acute and chronic GVHD occurred in 9 (9/27, 33%) and 16 patients (16/27, 59%), respectively. Non-relapse mortality at days 100 and 365 was 3 and 17%, respectively. The pharmacokinetics of i.v. BU showed close inter- and intrapatient consistency; the area under the plasma concentration–time curve of the first administration remained at less than 1500 μmol min/l in 27 of the 29 patients (93%), and between 900 and 1350 μmol min/l in 22 patients (73%). As all of the profiles overlap with data from non-Japanese patients, we conclude that racial factors may not seriously influence the bioactivity of i.v. BU.
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Acknowledgements
We thank Kirin Pharma Co. Ltd. (Japan) and PDL Bio Pharma Inc. (USA) for their support for this study. This study was conducted as a pivotal trial supported by Kirin Pharma Co. Ltd., Tokyo, Japan.
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Kim, SW., Mori, Si., Tanosaki, R. et al. Busulfex (i.v. BU) and CY regimen before SCT: Japanese-targeted phase II pharmacokinetics combined study. Bone Marrow Transplant 43, 611–617 (2009). https://doi.org/10.1038/bmt.2008.372
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DOI: https://doi.org/10.1038/bmt.2008.372
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