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供者选择具有中央元件的杀伤细胞免疫球蛋白样受体 B 单倍型可改善 HLA 相合同胞造血干细胞移植后的结局。

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.

出版信息

Biol Blood Marrow Transplant. 2014 Jan;20(1):98-105.

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.

摘要

造血干细胞移植(HSCT)后,受者 HLA 细胞中的自然杀伤(NK)细胞同种异体反应受供者 NK 细胞上的杀伤细胞免疫球蛋白样受体(KIR)调节。KIR 对 HSCT 结果的影响存在争议,尤其是在接受 HLA 完全匹配的同胞 HSCT 的患者中。在这项研究中,我们对 219 对接受 HLA 完全匹配的同胞 HSCT 治疗髓系和淋巴系恶性肿瘤的患者-供者对进行了为期 5 年的回顾性研究,以研究 KIR 和 HLA 基因型对 HSCT 结果的影响。我们发现,这些配对中有 39.7%(219 对中的 87 对)存在 KIR 不匹配,具有更好的总生存率(OS)和降低的 III 级至 IV 级急性移植物抗宿主病(aGVHD),尤其是在急性髓系白血病(AML)患者中。Bx1 供体 KIR 基因型在端粒区域具有单倍型 B 是 OS 和无复发生存(RFS)的危险因素。供体着丝粒(c)和端粒(t)KIR 单倍型分析显示,与 cA-tA 或 cA-tB 相比,供体 KIR cB-tA/tB 与改善的 OS 和 RFS 相关。此外,KIR 中心母型(Cen-B)的供体 KIR B 单倍型是改善 OS 和 RFS 的独立有益因素,并可防止 HSCT 后复发。在 AML 患者中,与 HLA-C2 组相比,HLA-C1 组 aGVHD 的发生明显降低,尽管在急性淋巴细胞白血病或慢性髓系白血病患者中未观察到这种作用。我们的研究结果表明,KIR 可能会影响结果,并且具有 Cen-B 的供体 KIR 单倍型为 HLA 完全匹配的同胞 HSCT 带来显著的生存获益。

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