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Association of iKIR-mismatch model and donor aKIRs with better outcome in haploidentical hematopoietic stem cell transplantation for acute myeloid leukemia
OBJECTIVES: Killer 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 tra...
Autores principales: | , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Frontiers Media S.A.
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9904326/ https://www.ncbi.nlm.nih.gov/pubmed/36761162 http://dx.doi.org/10.3389/fimmu.2022.1091188 |
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author | Zhang, Yu Ye, Chenjing Zhu, Haojie Zhuang, Youran Chen, Shaozhen Weng, Yingxi Ren, Jinhua Luo, Xiaofeng Zheng, Jing Zheng, Xiaoyun Li, Jing Lan, Lingqiong Xie, Yongxin Han, Zhongchao Hu, Jianda Yang, Ting |
author_facet | Zhang, Yu Ye, Chenjing Zhu, Haojie Zhuang, Youran Chen, Shaozhen Weng, Yingxi Ren, Jinhua Luo, Xiaofeng Zheng, Jing Zheng, Xiaoyun Li, Jing Lan, Lingqiong Xie, Yongxin Han, Zhongchao Hu, Jianda Yang, Ting |
author_sort | Zhang, Yu |
collection | PubMed |
description | OBJECTIVES: Killer 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. METHOD: Data 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. RESULTS: Both 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. CONCLUSIONS: Both 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. |
format | Online Article Text |
id | pubmed-9904326 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-99043262023-02-08 Association of iKIR-mismatch model and donor aKIRs with better outcome in haploidentical hematopoietic stem cell transplantation for acute myeloid leukemia Zhang, Yu Ye, Chenjing Zhu, Haojie Zhuang, Youran Chen, Shaozhen Weng, Yingxi Ren, Jinhua Luo, Xiaofeng Zheng, Jing Zheng, Xiaoyun Li, Jing Lan, Lingqiong Xie, Yongxin Han, Zhongchao Hu, Jianda Yang, Ting Front Immunol Immunology OBJECTIVES: Killer 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. METHOD: Data 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. RESULTS: Both 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. CONCLUSIONS: Both 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. Frontiers Media S.A. 2023-01-24 /pmc/articles/PMC9904326/ /pubmed/36761162 http://dx.doi.org/10.3389/fimmu.2022.1091188 Text en Copyright © 2023 Zhang, Ye, Zhu, Zhuang, Chen, Weng, Ren, Luo, Zheng, Zheng, Li, Lan, Xie, Han, Hu and Yang https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
spellingShingle | Immunology Zhang, Yu Ye, Chenjing Zhu, Haojie Zhuang, Youran Chen, Shaozhen Weng, Yingxi Ren, Jinhua Luo, Xiaofeng Zheng, Jing Zheng, Xiaoyun Li, Jing Lan, Lingqiong Xie, Yongxin Han, Zhongchao Hu, Jianda Yang, Ting Association of iKIR-mismatch model and donor aKIRs with better outcome in haploidentical hematopoietic stem cell transplantation for acute myeloid leukemia |
title | Association of iKIR-mismatch model and donor aKIRs with better outcome in haploidentical hematopoietic stem cell transplantation for acute myeloid leukemia |
title_full | Association of iKIR-mismatch model and donor aKIRs with better outcome in haploidentical hematopoietic stem cell transplantation for acute myeloid leukemia |
title_fullStr | Association of iKIR-mismatch model and donor aKIRs with better outcome in haploidentical hematopoietic stem cell transplantation for acute myeloid leukemia |
title_full_unstemmed | Association of iKIR-mismatch model and donor aKIRs with better outcome in haploidentical hematopoietic stem cell transplantation for acute myeloid leukemia |
title_short | Association of iKIR-mismatch model and donor aKIRs with better outcome in haploidentical hematopoietic stem cell transplantation for acute myeloid leukemia |
title_sort | association of ikir-mismatch model and donor akirs with better outcome in haploidentical hematopoietic stem cell transplantation for acute myeloid leukemia |
topic | Immunology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9904326/ https://www.ncbi.nlm.nih.gov/pubmed/36761162 http://dx.doi.org/10.3389/fimmu.2022.1091188 |
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