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Busulfan concentration and graft rejection in pediatric patients undergoing hematopoietic stem cell transplantation

2002; Springer Nature; Volume: 30; Issue: 3 Linguagem: Inglês

10.1038/sj.bmt.1703612

1476-5365

Jeannine S. McCune, Ted Gooley, JP Gibbs, JE Sanders, EW Petersdorf, FR Appelbaum, Claudio Anasetti, Linda J. Risler, Debbie Sultan, JT Slattery,

Renal Transplantation Outcomes and Treatments

We retrospectively analyzed the relationship between busulfan average steady-state plasma concentration (C(SS)) 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 C(SS) (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 C(SS). Severe (grade 3 or 4) regimen-related toxicity (RRT) occurred in four patients. Ten patients (19%) had a busulfan C(SS) 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 C(SS) 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 C(SS) and better definition of the contribution of activated cyclophosphamide metabolites to toxicity.