Cytotoxic T-lymphocyte antigen 4 haplotype correlates with relapse and survival after allogeneic hematopoietic SCT

M. Murase, T. Nishida, M. Onizuka, Y. Inamoto, K. Sugimoto, N. Imahashi, M. Murata, K. Miyamura, Y. Kodera, H. Inoko, T. Naoe

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12 Citations (Scopus)

Abstract

CTLA-4 is a negative regulator of activated T cells and the association of CTLA-4 polymorphisms with autoimmune diseases and transplant outcome has been reported. We evaluated the effect of donor CTLA-4 polymorphisms on outcome after allogeneic hematopoietic SCT (HSCT). We analyzed 147 Japanese HLA-matched sibling recipients and their donors who had undergone allogeneic HSCT. Genotyping of three single-nucleotide polymorphisms in CTLA-4 (-318, +49, CT60) was performed using TaqMan-PCR. According to the international HapMap database, only these three CTLA-4 haplotypes, classified as C-G-G, C-A-A and T-A-G, are present in the Japanese population. In this study, percentage expression of the C-G-G, C-A-A and T-A-G haplotypes was 59.5, 30.6 and 9.9%, respectively. Recipients of the C-A-A haplotype donor showed a significantly lower risk of relapse (HR: 0.54, 95% CI: 0.30-0.97, P=.040) and a trend toward higher OS (HR: 0.61, 95% CI: 0.36-1.0, P=.054) than did recipients of a donor without the C-A-A haplotype. The presence or absence of the C-A-A haplotype did not affect GVHD or non-relapse mortality. As the presence of the C-A-A haplotype reduced relapse risk and improved survival after allogeneic HSCT, this CTLA-4 haplotype may provide useful information for donor selection.

Original languageEnglish
Pages (from-to)1444-1449
Number of pages6
JournalBone Marrow Transplantation
Volume46
Issue number11
DOIs
Publication statusPublished - 11-2011
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Hematology
  • Transplantation

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