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.
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26 November 2019
In the original article of Terakura et al., the COI disclosure were missing.
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Acknowledgements
This work was supported by Grants from the Japan Society for the Promotion of Science (JSPS) KAKENHI (18K08351 to S.T. and 18K08321 to M.M.).
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12185_2019_2741_MOESM1_ESM.pdf
Supplementary file 1 Figure S1 Comparisons of first dose AUC of BU according to GSTM1 and GSTT1 genotypes stratified with GSTA1 genotype. (A) GSTA1*A/*A patients and (B) GSTA1*A/*B and *B/*B patients. One-way ANOVA. NS, not significant (PDF 43 kb)
12185_2019_2741_MOESM2_ESM.pdf
Supplementary file 2 Figure S2 Impact of first dose AUC and BU-dose modification to the maximum total-bilirubin during first month after stem cell transplantation. (A) First dose AUC, (B) BU-dose modification. Mann-Whitney U test. **P<0.01, *P<0.05, NS, not significant (PDF 40 kb)
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Terakura, S., Onizuka, M., Fukumoto, M. et al. Analysis of glutathione S-transferase and cytochrome P450 gene polymorphism in recipients of dose-adjusted busulfan-cyclophosphamide conditioning. Int J Hematol 111, 84–92 (2020). https://doi.org/10.1007/s12185-019-02741-8
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DOI: https://doi.org/10.1007/s12185-019-02741-8