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Title: KIR2DS4 and Its Variant KIR1D Are Associated with Acute Graft-versus-Host Disease, Cytomegalovirus, and Overall Survival after Sibling-Related HLA-Matched Transplantation in Patients with Donors with KIR Gene Haplotype A.
Author: Wu X, Yao Y, Bao X, Zhou H, Tang X, Han Y, Ma X, Liu Y, Chen J, Zhou H, Jing S, Gu B, Xu Y, Sun A, He J, Wu D.
Journal: Biol Blood Marrow Transplant; 2016 Feb; 22(2):220-225. PubMed ID: 26476204.
Abstract:
Outcomes for hematopoietic stem cell transplantation (HSCT) in various donor and recipient killer immunoglobulin-like receptor (KIR) genotypes have been studied extensively. The associations between KIR2DS4 and its variant KIR1D with outcomes of HSCT from a sibling-related HLA-matched donor with KIR haplotype A have not been explored, however. To study this, we genotyped donor-recipient pairs and divided 165 recipients of HSCT from a KIR gene haplotype A donor into 3 groups: 2DS4+/2DS4+ (2 intact KIR2DS4 alleles), 2DS4+/1D+ (heterozygous), and 1D+/1D+ (homozygous for the deletion variant KIR1D). No difference in the recovery of neutrophils and platelets among the 3 groups was observed. The cumulative incidence of grade III-IV acute graft-versus-host disease (aGVHD) within day +100 was 28.94% in the 2DS4+/2DS4+ group, 14.11% in the 2DS4+/1D+ group, and 44.44% in the 1D+/1D+ group (P = .0159). Multivariate analysis identified 1D+/1D+ as an independent risk factor for aGVHD (hazard ratio [HR], 4.221; 95% confidence interval [CI], 1.470 to 12.124; P = .007). In contrast, the cumulative incidences of chronic GVHD, 3-year cumulative relapse, and treatment-related mortality did not differ significantly among the 3 groups. The rate of cytomegalovirus (CMV) reactivation was 46.96% in the 2DS4+/2DS4+ group, 20.16% in the 2DS4+/1D+ group, and 53.25% in the 1D+/1D+ group (P = .0017). Multivariate analysis identified 2DS4+/1D+ as an independent protective factor for CMV reactivation (HR, 0.268; 95% CI, 0.125 to 0.574; P = .001). Although overall survival (OS) did not differ among the groups in the first year, the 2DS4(+)/2DS4(+) group had significantly better OS than the other groups after 1 year (P = .0361). In patients with advanced-stage disease, the 3-year probability of disease-free survival was 51.06% in the 2DS4+/2DS4+ group, 34.01% in the 2DS4+/1D+ group, and 0% in the 1D+/1D+ group (P = .0314). Collectively, our data suggest that the KIR 2DS4/1D allelic variance is associated with the outcome of sibling-related HLA-matched HSCT, and that donor subclassification of KIR 2DS4/1D alleles should be considered in this setting.

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