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.
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.
authors.affiliation: Department of Hematology, Jiangsu Institute of Hematology, Collaborative Innovation Center of Hematology, First Affiliated Hospital of Soochow University, Suzhou, China.
authors.forename: Xiaojin
authors.initials: X
authors.lastname: Wu
authors.affiliation: Department of Hematology, Jiangsu Institute of Hematology, Collaborative Innovation Center of Hematology, First Affiliated Hospital of Soochow University, Suzhou, China.
authors.forename: Yao
authors.initials: Y
authors.lastname: Yao
authors.affiliation: Department of Hematology, Jiangsu Institute of Hematology, Collaborative Innovation Center of Hematology, First Affiliated Hospital of Soochow University, Suzhou, China; HLA Laboratory, Jiangsu Institute of Hematology, First Affiliated Hospital of Soochow University, Suzhou, China.
authors.forename: Xiaojing
authors.initials: X
authors.lastname: Bao
authors.affiliation: Department of Hematology, Jiangsu Institute of Hematology, Collaborative Innovation Center of Hematology, First Affiliated Hospital of Soochow University, Suzhou, China.
authors.forename: Huifeng
authors.initials: H
authors.lastname: Zhou
authors.affiliation: Department of Hematology, Jiangsu Institute of Hematology, Collaborative Innovation Center of Hematology, First Affiliated Hospital of Soochow University, Suzhou, China.
authors.forename: Xiaowen
authors.initials: X
authors.lastname: Tang
authors.affiliation: Department of Hematology, Jiangsu Institute of Hematology, Collaborative Innovation Center of Hematology, First Affiliated Hospital of Soochow University, Suzhou, China.
authors.forename: Yue
authors.initials: Y
authors.lastname: Han
authors.affiliation: Department of Hematology, Jiangsu Institute of Hematology, Collaborative Innovation Center of Hematology, First Affiliated Hospital of Soochow University, Suzhou, China.
authors.forename: Xiao
authors.initials: X
authors.lastname: Ma
authors.affiliation: Department of Hematology, Jiangsu Institute of Hematology, Collaborative Innovation Center of Hematology, First Affiliated Hospital of Soochow University, Suzhou, China.
authors.forename: Yuejun
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Department of Hematology, Jiangsu Institute of Hematology, Collaborative Innovation Center of Hematology, First Affiliated Hospital of Soochow University, Suzhou, China.
authors.forename: Jia
authors.initials: J
authors.lastname: Chen
authors.affiliation: Department of Hematology, Jiangsu Institute of Hematology, Collaborative Innovation Center of Hematology, First Affiliated Hospital of Soochow University, Suzhou, China.
authors.forename: Haixia
authors.initials: H
authors.lastname: Zhou
authors.affiliation: Department of Hematology, Jiangsu Institute of Hematology, Collaborative Innovation Center of Hematology, First Affiliated Hospital of Soochow University, Suzhou, China.
authors.forename: Song
authors.initials: S
authors.lastname: Jing
authors.affiliation: Department of Hematology, Jiangsu Institute of Hematology, Collaborative Innovation Center of Hematology, First Affiliated Hospital of Soochow University, Suzhou, China.
authors.forename: Bing
authors.initials: B
authors.lastname: Gu
authors.affiliation: Department of Hematology, Jiangsu Institute of Hematology, Collaborative Innovation Center of Hematology, First Affiliated Hospital of Soochow University, Suzhou, China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Xu
authors.affiliation: Department of Hematology, Jiangsu Institute of Hematology, Collaborative Innovation Center of Hematology, First Affiliated Hospital of Soochow University, Suzhou, China.
authors.forename: Aining
authors.initials: A
authors.lastname: Sun
authors.affiliation: Department of Hematology, Jiangsu Institute of Hematology, Collaborative Innovation Center of Hematology, First Affiliated Hospital of Soochow University, Suzhou, China; HLA Laboratory, Jiangsu Institute of Hematology, First Affiliated Hospital of Soochow University, Suzhou, China. Electronic address: junhe1964@163.com.
authors.forename: Jun
authors.initials: J
authors.lastname: He
authors.affiliation: Department of Hematology, Jiangsu Institute of Hematology, Collaborative Innovation Center of Hematology, First Affiliated Hospital of Soochow University, Suzhou, China. Electronic address: wudepei@medmail.com.cn.
authors.forename: Depei
authors.initials: D
authors.lastname: Wu
mesh_terms: D000293:Adolescent; D000328:Adult; D002648:Child; D003587:Cytomegalovirus / Q000235:genetics*; D005260:Female; D005838:Genotype; D006086:Graft vs Host Disease / Q000235:genetics*; D006239:Haplotypes; D018380:Hematopoietic Stem Cell Transplantation / Q000379:methods* / Q000401:mortality; D006648:Histocompatibility; D006801:Humans; D008297:Male; D008875:Middle Aged; D054340:Receptors, KIR / Q000235:genetics* / Q000378:metabolism*; D035781:Siblings; D016019:Survival Analysis; D014019:Tissue Donors; D019172:Transplantation Conditioning / Q000379:methods*; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: C473953:KIR2DS4 protein, human; D054340:Receptors, KIR
keywords: HLA-matched sibling donor; Hematopoietic stem cell transplantation; KIR1D; KIR2DS4