title: The beneficial impact of missing KIR ligands and absence of donor KIR2DS3 gene on outcome following unrelated hematopoietic SCT for myeloid leukemia in the Chinese population.
abstract: The effect of natural killer (NK) cell alloreactivity on the outcome of unrelated hematopoietic SCT (HSCT) remains a topic of debate. NK cell alloreactivity after allogeneic HSCT is regulated by killer-cell Ig-like receptors (KIRs). To investigate the influence of KIRs on outcome after unrelated HSCT, we retrospectively analyzed the HLA and KIR genotypes of 116 donor-recipient pairs. We found that missing KIR ligands in recipients were significantly associated with a decreased leukemic relapse risk (P=0.019, HR=0.329), mainly in myeloid disease (P=0.003, HR=0.193). This beneficial effect was seen in AML/myelodysplastic syndrome and also in chronic myeloid leukemia. In myeloid disease, missing KIR ligands also improved 5-year OS (P=0.034, HR=0.430) and disease-free survival (DFS) (P=0.024, HR=0.445). Meanwhile, the presence of donor-activating KIR2DS3 gene was associated with increased relapse risk (P=0.003, HR=5.046), decreased OS (P=0.004, HR=3.181) and DFS (P=0.003, HR=2.919) in myeloid disease. No effect was seen in patients with lymphoid disease. Our study indicated that, in unrelated HSCT for myeloid leukemia, missing KIR ligands in recipients offered a lower relapse risk and a long-term survival advantage. The presence of KIR2DS3 in the donor was an important risk factor for myeloid leukemia.
authors.affiliation: Bone Marrow Transplantation Center, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China.
authors.forename: G Q
authors.initials: GQ
authors.lastname: Wu
authors.forename: Y M
authors.initials: YM
authors.lastname: Zhao
authors.forename: X Y
authors.initials: XY
authors.lastname: Lai
authors.forename: Y
authors.initials: Y
authors.lastname: Luo
authors.forename: Y M
authors.initials: YM
authors.lastname: Tan
authors.forename: J M
authors.initials: JM
authors.lastname: Shi
authors.forename: L
authors.initials: L
authors.lastname: Li
authors.forename: W Y
authors.initials: WY
authors.lastname: Zheng
authors.forename: J
authors.initials: J
authors.lastname: Zhang
authors.forename: X R
authors.initials: XR
authors.lastname: Hu
authors.forename: A Y
authors.initials: AY
authors.lastname: Jin
authors.forename: J S
authors.initials: JS
authors.lastname: He
authors.forename: W Z
authors.initials: WZ
authors.lastname: Xie
authors.forename: X J
authors.initials: XJ
authors.lastname: Ye
authors.forename: Z
authors.initials: Z
authors.lastname: Cai
authors.forename: M F
authors.initials: MF
authors.lastname: Lin
authors.forename: H
authors.initials: H
authors.lastname: Huang
mesh_terms: D000293:Adolescent; D000328:Adult; D002648:Child; D002681:China / Q000453:epidemiology; D005260:Female; D005838:Genotype; D006086:Graft vs Host Disease / Q000453:epidemiology / Q000235:genetics; D006680:HLA Antigens / Q000235:genetics*; D018380:Hematopoietic Stem Cell Transplantation / Q000401:mortality; D006801:Humans; D007938:Leukemia / Q000235:genetics / Q000628:therapy; D007951:Leukemia, Myeloid / Q000235:genetics / Q000628:therapy*; D008024:Ligands; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000453:epidemiology / Q000235:genetics; D054340:Receptors, KIR / Q000819:agonists* / Q000235:genetics; D012189:Retrospective Studies; D012307:Risk Factors; D016019:Survival Analysis; D014019:Tissue Donors; D055815:Young Adult
chemical_list: D006680:HLA Antigens; C541358:KIR2DS3 protein, human; D008024:Ligands; D054340:Receptors, KIR