Pharmacogenetic Analysis of Liver Toxicity after Busulfan/Cyclophosphamide-based Allogeneic Hematopoietic Stem Cell Transplantation

Abstract

The aim of this study was to evaluate the impact of genomic polymorphisms of methylene-tetrahydrofolate-reductase (MTHFR-C677T, MTHFR-A1298C) and various glutathione S-transferases (GSTP1-Ile105Val, GSTA1*a/b, GSTM1, GSTT1) on the occurrence of liver toxicity in patients receiving allogeneic hematopoietic stem cell transplantation (HSCT). Patients and Methods: Eighty-four adult patients were enrolled in this retrospective study. All patients were treated with busulfan/cyclophosphamide as a conditioning regimen and received cyclosporine and short-course MTX for GvHD prophylaxis. Genotyping was performed using PCR based restriction-fragment-length-polymorphism (RFLP) techniques. Results: Multivariate analysis identified the MTHFR-A1298C polymorphism as an independent predictor for maximum levels of bilirubin (p=0.0025) and duration of hyperbilirubinaemia (p=0.013). Furthermore, there was an association between this polymorphism and the occurrence of the sinusoidal obstruction syndrome (SOS) (p=0.048). No significant associations between the MTHFR-C677T or the various GST polymorphisms and liver toxicity were observed. Conclusion: The MTHFR-A1298C polymorphism might be associated with liver toxicity in patients receiving allogeneic HSCT.