Efficacy and early complications of intravenous busulfan in children with thalassemia undergoing hematopoietic stem cell transplantation

Abstract

Hematol Oncol Stem Cell Ther 1(3) July 2008 hemoncstem.edmgr.com 189 Oral busulfan (BU) and intravenous cycloa phosphamide (CY) are standard conditiona ing chemotherapeutic agents for allogeneic hematopoietic stem cell transplantation (HSCT) in thalassemic patients.1 Pharmacokinetic studies of oral BU demonstrate wide intera and intraindividual varia ability in drug levels.2,3 The association between steadya state plasma concentrations and areaaunderatheacurve (AUC) values for busulfan and the occurrence of graft failure, venoaocclusive disease (VOD), and early mora tality have been reported.4a6 Graft rejection is a coma mon adverse event found in thalassemic patients una dergoing HSCT.1,7 The unpredictability of busulfan levels may further increase the high incidence of graft rejection known to occur in patients with thalassemia. The use of intravenous busulfan (IVBU) may overa come the variability of plasma drug levels leading to increased favorable outcomes after HSCT. Andersson et al8 initially showed consistent AUCs of IVBU in adults with hematologic malignancies without increasa ing side effects. Nguyen et al9 demonstrated that fixed dosing based on the actual weight of pediatric patients is well correlated with targeted AUC values. With these recommended dosages, IVBU can be successfully used without therapeutic drug monitoring.10 These data may enable clinicians to use IVBU conveniently in centers where pharmacokinetic studies can not be performed. Therefore, this study is intended to explore the efficacy and toxicity of IVBU as a part of a conditioning regia men in thalassemic children undergoing HSC T witha out drug monitoring.