Abstract
We retrospectively analyzed the relationship between busulfan average steady-state plasma concentration (CSS) and graft rejection in 53 children receiving busulfan/cyclophosphamide (BU/CY) preparative regimens prior to hematopoietic stem cell transplantation (HSCT). Patients received a total oral busulfan dose of 11 to 28 mg/kg followed by a total cyclophosphamide dose of 120 to 335 mg/kg in preparation for allogeneic grafts (HLA-matched or HLA partially matched sibling, parent or unrelated donor). Graft rejection occurred in eight (15%) patients. Busulfan CSS (P = 0.0024) was the only statistically significant predictor of rejection on univariate logistic regression analysis, with the risk of rejection decreasing with an increase in busulfan CSS. Severe (grade 3 or 4) regimen-related toxicity (RRT) occurred in four patients. Ten patients (19%) had a busulfan CSS higher than 900 ng/ml, one of whom had severe RRT. Higher and variable doses of cyclophosphamide may explain the lack of a relationship between busulfan CSS and RRT in children. It may be possible to improve the outcome of HSCT in pediatric patients receiving the BU/CY regimen through optimization of busulfan CSS and better definition of the contribution of activated cyclophosphamide metabolites to toxicity.
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McCune, J., Gooley, T., Gibbs, J. et al. Busulfan concentration and graft rejection in pediatric patients undergoing hematopoietic stem cell transplantation. Bone Marrow Transplant 30, 167–173 (2002). https://doi.org/10.1038/sj.bmt.1703612
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DOI: https://doi.org/10.1038/sj.bmt.1703612
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