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CTLA‐4 polymorphism rs231775: Influence on relapse and survival after allogeneic hematopoietic stem cell transplantation in childhood
Author(s) -
Hammrich Judith,
Wittig Susan,
Ernst Thomas,
Gruhn Bernd
Publication year - 2019
Publication title -
european journal of haematology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.904
H-Index - 84
eISSN - 1600-0609
pISSN - 0902-4441
DOI - 10.1111/ejh.13200
Subject(s) - hematopoietic stem cell transplantation , genotype , single nucleotide polymorphism , transplantation , ctla 4 , medicine , snp , immunology , oncology , stem cell , haematopoiesis , t cell , immune system , biology , gene , genetics
Objective Relapse following allogeneic hematopoietic stem cell transplantation (HSCT) is still linked to a poor prognosis. Mainly, donor`s T‐cells mediate the graft‐versus‐leukemia effect. Cytotoxic T‐lymphocyte antigen‐4 (CTLA‐4) is an inhibitory molecule which down‐regulates T‐cell activation. Single nucleotide polymorphism (SNP) in CTLA‐4 may have an effect on immune response. Methods Eighty‐eight children with acute leukemia and their donors were genotyped of CTLA‐4 gene for rs231775. We searched for an association of CTLA‐4 SNP with relapse and survival after allogeneic HSCT. Results We identified a significantly reduced relapse rate in children who received a transplant from a donor with the CTLA‐4 genotypes AG or GG in comparison with genotype AA of rs231775 (19% vs 40%, P = 0.026). In addition, we observed a significant difference in event‐free survival (EFS) depending on the donor´s genotype. The EFS was 70% or 46% if the patient was transplanted from a donor with CTLA‐4 genotype AG/GG or AA, respectively ( P = 0.025). In multivariate analysis, CTLA‐4 genotype was an independent risk factor for relapse rate ( P = 0.028). Conclusion This study suggests that CTLA‐4 polymorphism rs231775 is relevant for relapse and survival after allogeneic HSCT in childhood and should be further investigated in clinical trials.