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

Authors
  • Terakura, S
  • Murata, M
  • Nishida, T
  • Emi, N
  • Akatsuka, Y
  • Morishima, Y
  • Kodera, Y
  • Naoe, T
Type
Published Article
Journal
Bone Marrow Transplantation
Publisher
Springer Nature
Publication Date
Feb 01, 2006
Volume
37
Issue
4
Pages
381–386
Identifiers
PMID: 16415899
Source
Medline
License
Unknown

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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