CTLA-4 polymorphism rs231775: Influence on relapse and survival after allogeneic hematopoietic stem cell transplantation in childhood.

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.