title: Donor selection for KIR B haplotype of the centromeric motifs can improve the outcome after HLA-identical sibling hematopoietic stem cell transplantation.
abstract: After hematopoietic stem cell transplantation (HSCT), natural killer (NK) cell alloreactivity in human leukocyte antigen (HLA) cell of recipients is regulated by killer immunoglobulin-like receptors (KIRs) on donor NK cells. The effect of KIRs on HSCT outcomes is controversial, particularly in those undergoing HLA-identical sibling HSCT. In this study, effects of KIR and HLA genotypes on the HSCT outcome were investigated in a 5-year retrospective study comprising 219 patient-donor pairs undergoing HLA-identical sibling HSCT for myeloid and lymphoid malignancies. We found that 39.7% (87/219) of these pairs who were KIR mismatched had better overall survival (OS) and reduced III-IV acute graft-versus-host disease (aGVHD), especially in acute myeloid leukemia (AML) patients. Bx1 donor KIR genotype with haplotype B on a telomeric region was a risk factor for the OS and relapse-free survival (RFS). Donor centromeric (c) and telomeric (t) KIR haplotype analysis showed that donor KIR cB-tA/tB was associated with improved OS and RFS compared with cA-tA or cA-tB. Furthermore, donor KIR B haplotype of the centromeric motifs (Cen-B) was an independent beneficial factor in improving OS and RFS and in protecting from relapse after HSCT. In AML patients, the occurrence of aGVHD was significantly lower in HLA-C1 group compared to that in HLA-C2 group, while such effect was not observed in patients with acute lymphoblastic leukemia or chronic myelogenous leukemia. Our results suggest that KIR could impact outcome and donor KIR haplotype with Cen-B confer significant survival benefits to HLA-identical sibling HSCT.
authors: Department of Hematology, Jiangsu Institute of Hematology, Key Laboratory of Thrombosis and Hemostasis of Ministry of Health, First Affiliated Hospital of Soochow University, Suzhou, 215006, Jiangsu, P.R.China.
authors: Huifen
authors: H
authors: Zhou
authors: Department of HLA Laboratory, Jiangsu Institute of Hematology, Key Laboratory of Thrombosis and Hemostasis of Ministry of Health, First Affiliated Hospital of Soochow University, Suzhou, 215006, Jiangsu, P.R.China.
authors: Xiaojing
authors: X
authors: Bao
authors: Department of Hematology, Jiangsu Institute of Hematology, Key Laboratory of Thrombosis and Hemostasis of Ministry of Health, First Affiliated Hospital of Soochow University, Suzhou, 215006, Jiangsu, P.R.China.
authors: Xiaojin
authors: X
authors: Wu
authors: Department of Hematology, Jiangsu Institute of Hematology, Key Laboratory of Thrombosis and Hemostasis of Ministry of Health, First Affiliated Hospital of Soochow University, Suzhou, 215006, Jiangsu, P.R.China.
authors: Xiaowen
authors: X
authors: Tang
authors: Department of Hematology, Jiangsu Institute of Hematology, Key Laboratory of Thrombosis and Hemostasis of Ministry of Health, First Affiliated Hospital of Soochow University, Suzhou, 215006, Jiangsu, P.R.China.
authors: Miao
authors: M
authors: Wang
authors: Department of Hematology, Jiangsu Institute of Hematology, Key Laboratory of Thrombosis and Hemostasis of Ministry of Health, First Affiliated Hospital of Soochow University, Suzhou, 215006, Jiangsu, P.R.China. Electronic address: wudepei@medmail.com.cn.
authors: Depei
authors: D
authors: Wu
authors: Department of HLA Laboratory, Jiangsu Institute of Hematology, Key Laboratory of Thrombosis and Hemostasis of Ministry of Health, First Affiliated Hospital of Soochow University, Suzhou, 215006, Jiangsu, P.R.China. Electronic address: junhe1964@163.com.
authors: Jun
authors: J
authors: He
keywords: Centromeric B; HSCT; KIR; haplotype; sibling