International Journal of Hematology

DOI: 10.1007/s12185-019-02741-8 Pages: 84-92

Analysis of glutathione S-transferase and cytochrome P450 gene polymorphism in recipients of dose-adjusted busulfan-cyclophosphamide conditioning

1. Japanese Red Cross Nagoya First Hospital, Department of Hematology

2. Nagoya University Graduate School of Medicine, Department of Hematology and Oncology

3. Tokai University School of Medicine, Department of Hematology and Oncology

4. Kitasato University, Division of Clinical Toxicology, Research and Education Center for Clinical Pharmacy, School of Pharmaceutical Sciences

5. Nagoya University Hospital, Department of Advanced Medicine

6. JA Aichi Konan Kosei Hospital, Department of Hematology and Oncology

7. Anjo Kosei Hospital, Department of Hematology and Oncology

8. Nagoya University Graduate School of Medicine, Department of HSCT Data Management/Biostatistics

Correspondence to:
Seitaro Terakura
Email: tseit@med.nagoya-u.ac.jp

Close

Abstract

Sporadic incidence of veno-occlusive disease (VOD) continues to occur, despite achievement of recommended busulfan (BU) concentrations after real-time BU dose adjustment. To explore the potential influence of glutathione S-transferase (GST) and cytochrome P450 (CYP) genotypes on plasma BU concentration, subsequent VOD, and transplant outcome, we assessed the polymorphisms of multiple GST and CYP genes. Fifty-five patients were included (median age 38 years; range 21–67). Of these, 49 received dose-adjusted BU/CY therapy. Twenty-six patients received transplants from human leukocyte antigen-identical siblings, 26 from unrelated donors. The GSTA1*A/*A genotype was significantly associated with lower BU first-dose area under curve (AUC1st). We found that patients with higher AUC1st showed a significantly higher serum total bilirubin during the first month after transplantation, but this was not necessarily associated with subsequent development of VOD. We further analyzed a possible association of GST and CYP polymorphisms and VOD development, and found none of the polymorphisms investigated was associated with VOD incidence. Regarding transplant outcomes, GSTM1-positive patients showed lower relapse rates and better overall survival in multivariate analyses. These results suggest that a GSTM1-positive genotype in patients receiving BU/CY conditioning protects against relapse of hematological malignancies after allogeneic hematopoietic stem cell transplantation.

To access the full text, please Sign in

If you have institutional access, please click here

Share the Knowledge