title: Donor selection for killer immunoglobulin-like receptors 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 HLA cells 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 of 219) of these pairs, which were KIR mismatched, had better overall survival (OS) and reduced grade III to 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 with that in HLA-C2 group, although 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: Huifen
authors: H
authors: Zhou
authors: Xiaojing
authors: X
authors: Bao
authors: Xiaojin
authors: X
authors: Wu
authors: Xiaowen
authors: X
authors: Tang
authors: Miao
authors: M
authors: Wang
authors: Depei
authors: D
authors: Wu
authors: Jun
authors: J
authors: He
mesh_terms: D000293:Adolescent; D000328:Adult; D002648:Child; D046148:Donor Selection; D005260:Female; D006086:Graft vs Host Disease / Q000517:prevention & control; D006680:HLA Antigens / Q000235:genetics / Q000276:immunology; D006239:Haplotypes; D019337:Hematologic Neoplasms / Q000235:genetics* / Q000276:immunology / Q000401:mortality / Q000628:therapy*; D018380:Hematopoietic Stem Cell Transplantation; D006650:Histocompatibility Testing; D006801:Humans; D008297:Male; D008875:Middle Aged; D019653:Myeloablative Agonists / Q000627:therapeutic use*; D011379:Prognosis; D054340:Receptors, KIR / Q000145:classification / Q000235:genetics / Q000276:immunology*; D012008:Recurrence; D012306:Risk; D035781:Siblings; D016019:Survival Analysis; D014019:Tissue Donors; D019172:Transplantation Conditioning; D014184:Transplantation, Homologous
chemical_list: D006680:HLA Antigens; D019653:Myeloablative Agonists; D054340:Receptors, KIR