Frontiers in Immunology (Jan 2023)

Association of iKIR-mismatch model and donor aKIRs with better outcome in haploidentical hematopoietic stem cell transplantation for acute myeloid leukemia

  • Yu Zhang,
  • Yu Zhang,
  • Yu Zhang,
  • Chenjing Ye,
  • Chenjing Ye,
  • Haojie Zhu,
  • Haojie Zhu,
  • Youran Zhuang,
  • Shaozhen Chen,
  • Shaozhen Chen,
  • Yingxi Weng,
  • Yingxi Weng,
  • Jinhua Ren,
  • Jinhua Ren,
  • Xiaofeng Luo,
  • Xiaofeng Luo,
  • Jing Zheng,
  • Jing Zheng,
  • Xiaoyun Zheng,
  • Xiaoyun Zheng,
  • Jing Li,
  • Jing Li,
  • Lingqiong Lan,
  • Lingqiong Lan,
  • Yongxin Xie,
  • Yongxin Xie,
  • Zhongchao Han,
  • Jianda Hu,
  • Jianda Hu,
  • Ting Yang,
  • Ting Yang

DOI
https://doi.org/10.3389/fimmu.2022.1091188
Journal volume & issue
Vol. 13

Abstract

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ObjectivesKiller cell immunoglobulin like receptor (KIR) can trigger the alloreactivity of NK cells. However, there is no clear consensus as to their function. Here, we investigated the potential influence of KIR mismatch and KIR alleles on the outcome of haploidentical hematopoietic stem cell transplantation (haplo-HSCT) in acute myeloid leukemia (AML) patients.MethodData from 79 AML patients treated with haplo-HSCT were retrospectively analyzed. HLA-C genotyping was determined by the PCR-rSSO method. KIR, HLA-A and HLA-B genotyping was performed by the PCR-SSP method. Cox proportional hazards model and Kaplan-Meier survival curves were used for analysis.ResultsBoth KIR ligand mismatch (KLM) group and KIR receptor-ligand mismatch (RLM) group were associated with a decreased risk in aGVHD and relapse rate (RR), and better overall survival (OS) compared to the KIR ligand matching and receptor-ligand matching groups, respectively (aGVHD: KLM: p=0.047, HR:0.235; RLM: p<0.001, HR:0.129; RR: KLM: p=0.049, HR:0.686, RLM: p=0.017, HR:0.200;OS:KLM: p=0.012, HR: 0.298, RLM: p=0.021, HR:0.301). RLM was more accurate at predicting relapse and aGVHD compared with KLM (aGVHD: p=0.009; RR: p=0.039). Patients with greater number of donor activating KIRs (aKIR) had a lower incidence of aGVHD and relapse, and the benefits correlated with the increase in the number of donor aKIRs (aGVHD: p=0.019, HR:0.156; RR: p=0.037, HR:0.211). Patients with RLM and the highest number of donor aKIRs had the lowest RR, lowest incidence of aGVHD and best OS.ConclusionsBoth KLM and RLM reduced the risk of aGVHD and relapse after haplo-HSCT in AML patients, and RLM showed superiority in predicting HSCT outcome. The synergistic effects of RLM and donor aKIRs can provide a better donor selection strategy to improve haplo-HSCT outcome in AML patients.

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