Effect of glutathione S-transferase genetic polymorphisms on busulfan pharmacokinetics and veno-occlusive disease in hematopoietic stem cell transplantation: A meta-analysis

This meta-analysis was conducted to derive an integrated conclusion about the influence of glutathione S-transferase (GST) genetic polymorphisms on busulfan pharmacokinetic (PK) parameters and veno-occlusive disease (VOD). Studies which analysed the effect of GST genetic polymorphisms on area under the curve (AUC), clearance (CL) or VOD were searched for and selected. A pooled analysis was conducted using Comprehensive Meta-Analysis programme. Nineteen studies were included in this meta-analysis. GSTA1*B and GSTM1 null genotypes significantly decreased CL_IV of busulfan (standardized difference in means (SDM) = −1.103; P = 0.019 and SDM = −0.418; P = 0.002, respectively). GSTA1*B significantly increased AUC_IV of busulfan (SDM = 0.832; P = 0.046), whereas GSTM1 did not (SDM = 0.155; P = 0.478). The PK parameters of oral busulfan did not differ according to GST genotype. GSTA1, GSTM1 and GSTP1 were not significantly associated with VOD occurrence. GSTA1 and GSTM1 genotypes affected CL_IV of busulfan, but only GSTA1 affected AUC_IV. There was no significant difference in the PK parameters of oral busulfan (CL_PO and AUC_PO) and VOD when only GST genotypes were considered.