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Autografting

Increased risk for treatment-related mortality after bone marrow transplantation in GSTM1-positive recipients

Bone Marrow Transplantation volume 37, pages 381–386 (2006)Cite this article

Abstract

Treatment-related mortality (TRM) is a major obstacle to successful allogeneic hematopoietic stem cell transplantation (HSCT). A variety of drugs are used in allogeneic HSCT, and a genetic polymorphism in metabolic enzymes could affect the metabolism of drugs and potentially influence TRM. Here, we focused attention on GSTM1 and GSTT1 enzymes, which metabolize chemotherapeutic agents, chemical carcinogens and by-products of oxidative stress and are absent from more than 50% of some populations. To assess the significance of homozygous GSTM1 and GSTT1 gene deletion in HSCT, we analyzed DNA from 373 patients with hematological disease and their HLA-identical unrelated bone marrow donors using PCR. Homozygous GSTM1 and GSTT1 gene deletions were observed in 56 and 45% of patients, respectively, and 57 and 46% of donors, respectively. There was no significant association between GSTT1 polymorphism and any outcome. However, a GSTM1-positive genotype in recipients was significantly associated with higher TRM and lower survival. These results suggest that a GSTM1-null genotype in recipients protects against TRM after allogeneic HSCT. Further studies are needed to elucidate a mechanism of increased risk for TRM in GSTM1-positive recipients.

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Acknowledgements

We thank the staff of transplant and donor centers, and JMDP. We also thank Dr Stanley R Riddell for critical reading of the manuscript. This work was supported by a grant from the Ministry of Health, Labour and Welfare of Japan (MM and YK).

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Authors and Affiliations

  1. Department of Hematology, Nagoya University Graduate School of Medicine, Nagoya, Japan

    S Terakura, M Murata, T Nishida, N Emi & T Naoe

  2. Division of Immunology, Aichi Cancer Center Research Institute, Nagoya, Japan

    Y Akatsuka

  3. Department of Hematology and Cell Therapy, Aichi Cancer Center Hospital, Nagoya, Japan

    Y Morishima

  4. Department of Hematology, Japanese Red Cross Nagoya First Hospital, Nagoya, Japan

    Y Kodera

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  1. S Terakura
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  2. M Murata
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Correspondence to M Murata.

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Terakura, S., Murata, M., Nishida, T. et al. Increased risk for treatment-related mortality after bone marrow transplantation in GSTM1-positive recipients. Bone Marrow Transplant 37, 381–386 (2006). https://doi.org/10.1038/sj.bmt.1705257

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