HLA-haploidentical allogeneic hematopoietic cell transplantation (allo-HCT) using post-transplantation cyclophosphamide (PT/Cy-haplo) is becoming the standard of care for patients without an HLA-matched related or unrelated donor. PT/Cy-haplo can give more patients the opportunity to undergo allo-HCT, because most patients have multiple available HLA-haploidentical related donor candidates. The optimal donor selection algorithm in the PT/Cy-haplo setting has not yet been established, however. To contribute to the establishment of a donor selection formula based on disease status and killer-cell immunoglobulin-like receptor (KIR) genotype, we retrospectively analyzed 91 patients who underwent PT/Cy-haplo at our institution. In both patients and donors, HLA allele genotyping was performed for HLA-A, -B, -C, and -DRB1, and 16 KIR genes were genotyped. Patients in complete remission (CR) who underwent PT/Cy-haplo from a KIR2DS1-positive donor had a significantly lower cumulative incidence of relapse (CIR) than those who underwent PT/Cy-haplo from a KIR2DS1-negative donor (1-year CIR: 0% versus 32.6%, P = .037; 2-year CIR: 9.2% versus 42%, P = .037). Moreover, PT/Cy-haplo from a KIR2DS1-positive donor was significantly associated with improved overall survival (OS) (1-year OS: 91.7% versus 58.7%, P = .010; 2-year OS: 83% versus 34%, P = .010). In contrast, in non-CR individuals, PT/Cy-haplo from KIR2DS1-positive donors did not significantly improve CIR or OS (1-year CIR: 56.5% versus 64.7%, P = .973; 2-year CIR: not reached versus 64.7%, Pnot evaluable; 1-year OS: 25.4% versus 20.6%, P = .418; 2-year OS: 5.1% versus 20.6%, P = .418). In addition, lower infused CD34+ cell dose, female-to-male transplantation, and acute myelogenous leukemia were significantly associated with increased risk of relapse and mortality. This study demonstrates that graft-versus-leukemia/tumor effects were exerted through donor KIR2DS1 at PT/Cy-haplo when patients have low tumor burdens. It would be worth examining the inclusion of donor KIR genotyping and disease status assessment in establishing optimal donor selection criteria for PT/Cy-haplo.

中文翻译：

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捐赠者 KIR2DS1 介导的减少复发和提高生存率取决于移植后环磷酰胺 HLA-单倍体移植时的缓解状态。

使用移植后环磷酰胺 (PT/Cy-haplo) 进行 HLA 半相合同种异体造血细胞移植 (allo-HCT) 正在成为没有 HLA 匹配的相关或无关供体的患者的护理标准。PT/Cy-haplo 可以让更多的患者有机会接受 allo-HCT，因为大多数患者都有多个可用的 HLA 半相合相关供体候选人。然而，尚未建立 PT/Cy-haplo 设置中的最佳供体选择算法。为了有助于建立基于疾病状态和杀伤细胞免疫球蛋白样受体 (KIR) 基因型的供体选择公式，我们回顾性分析了在我们机构接受 PT/Cy-haplo 的 91 名患者。在患者和供体中，对 HLA-A、-B、-C 和 -DRB1 进行了 HLA 等位基因基因分型，并对 16 个 KIR 基因进行了基因分型。从 KIR2DS1 阳性供体接受 PT/Cy-haplo 的完全缓解 (CR) 患者的累积复发率 (CIR) 明显低于从 KIR2DS1 阴性供体接受 PT/Cy-haplo 的患者（1 年CIR：0% 对 32.6%，P = .037；2 年 CIR：9.2% 对 42%，P = .037）。此外，来自 KIR2DS1 阳性供体的 PT/Cy-haplo 与改善的总生存期 (OS) 显着相关（1 年 OS：91.7% 对 58.7%，P = .010；2 年 OS：83% 对 34% , P = .010)。相比之下，在非 CR 个体中，来自 KIR2DS1 阳性供体的 PT/Cy-haplo 并未显着改善 CIR 或 OS（1 年 CIR：56.5% 对 64.7%，P = .973；2 年 CIR：未达到与 64.7% 相比，Pnot 可评估；1 年 OS：25.4% 与 20.6%，P = .418；2 年 OS：5.1% 与 20.6%，P = .418）。此外，注入的 CD34+ 细胞剂量更低，女性对男性的移植和急性髓性白血病与复发和死亡风险增加显着相关。这项研究表明，当患者的肿瘤负荷较低时，移植物抗白血病/肿瘤效应是通过 PT/Cy-haplo 的供体 KIR2DS1 发挥的。在建立 PT/Cy-haplo 的最佳供体选择标准时，值得研究包括供体 KIR 基因分型和疾病状态评估。