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iKIR-HLA C 配体减少使接受抗胸腺细胞球蛋白为基础的单倍体造血干细胞移植的髓系疾病患者的临床结局更差。

Decreased iKIR-HLA C Pair Confers Worse Clinical Outcomes for Patients With Myeloid Disease Receiving Antithymocyte Globulin-Based Haploidentical Hematopoietic Stem Cell Transplantation.

机构信息

Bone Marrow Transplantation Center, the First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China.

Institute of Hematology, Zhejiang University, Hangzhou, China.

出版信息

Front Immunol. 2021 Feb 4;11:614488. doi: 10.3389/fimmu.2020.614488. eCollection 2020.

Abstract

Hematopoietic stem cell transplantation (HSCT) is a curative therapy for patients with malignant hematologic diseases. Killer immunoglobin-like receptor (KIR) expressed by NK cells is closely associated with the transplant outcomes, and it has been widely explored and debated for a few decades. Recently published studies have revealed that inhibitory KIRs (iKIRs) are educated by their cognate human lymphocyte antigen (HLA) ligands, and that decreased iKIR-HLA pairs post-transplantation may indicate a reduced NK cell function and impaired control of the primary disease. However, this theory still needs to be validated by additional clinical studies. Here we conducted a retrospective analysis of 246 patients who received haploidentical (haplo)-HSCT at our treatment center between January 2015 and June 2018. Our data suggests that decreased iKIR-HLA C pair post-HSCT correlated with a significantly higher risk of relapse [hazard risk (HR) = 2.95, p = 0.019] and reduced overall survival (OS) (HR = 3.74, p = 0.001) and disease-free survival (DFS) (HR = 4.05, p = 0.0004) in patients with myeloid disease. In conclusion, decreased iKIR-HLA C pair should be avoided during anti-thymocyte globulin (ATG)-based haplo-HSCT, especially for patients with myeloid disease.

摘要

造血干细胞移植(HSCT)是治疗恶性血液病患者的一种有治愈可能的疗法。NK 细胞表达的杀伤细胞免疫球蛋白样受体(KIR)与移植结果密切相关,几十年来一直受到广泛的探索和争论。最近发表的研究表明,抑制性 KIR(iKIR)受其同源人类淋巴细胞抗原(HLA)配体的教育,移植后 iKIR-HLA 对减少可能表明 NK 细胞功能降低,原发性疾病控制受损。然而,这一理论仍需要更多的临床研究来验证。在这里,我们对 2015 年 1 月至 2018 年 6 月在我们治疗中心接受半相合(haplo)-HSCT 的 246 例患者进行了回顾性分析。我们的数据表明,HSCT 后 iKIR-HLA C 对减少与髓系疾病患者复发风险显著增加相关[风险比(HR)=2.95,p=0.019],总生存(OS)(HR=3.74,p=0.001)和无病生存(DFS)(HR=4.05,p=0.0004)降低。总之,在基于抗胸腺细胞球蛋白(ATG)的半相合 HSCT 中,应避免 iKIR-HLA C 对减少,特别是对于髓系疾病患者。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1346/7901980/27603f5fece8/fimmu-11-614488-g001.jpg

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