Department of Hematology, Graduate School of Medicine, Osaka City University, Osaka, Japan.
Department of Hematology, Graduate School of Medicine, Osaka City University, Osaka, Japan.
Biol Blood Marrow Transplant. 2020 Apr;26(4):723-733. doi: 10.1016/j.bbmt.2019.12.765. Epub 2019 Dec 31.
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.
HLA 单倍体相合异基因造血细胞移植（allo-HCT）联合移植后环磷酰胺（PT/Cy-haplo）已成为无 HLA 匹配相关或无关供体患者的标准治疗方法。PT/Cy-haplo 可以为更多患者提供 allo-HCT 的机会，因为大多数患者有多个可供选择的 HLA 单倍体相合相关供者。然而，PT/Cy-haplo 中的最佳供者选择算法尚未建立。为了基于疾病状态和杀伤细胞免疫球蛋白样受体（KIR）基因型建立供者选择公式，我们回顾性分析了在我院接受 PT/Cy-haplo 的 91 例患者。在患者和供者中，均对 HLA-A、-B、-C 和-DRB1 进行了 HLA 等位基因基因分型，对 16 个 KIR 基因进行了基因分型。从 KIR2DS1 阳性供者接受 PT/Cy-haplo 的完全缓解（CR）患者的累积复发率（CIR）明显低于从 KIR2DS1 阴性供者接受 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 阳性供者的 PT/Cy-haplo 与改善总体生存率（OS）显著相关（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 阳性供者的 PT/Cy-haplo 并未显著改善 CIR 或 OS（1 年 CIR：56.5%对 64.7%，P=.973；2 年 CIR：未达到对 64.7%，Pnot 可评估；1 年 OS：25.4%对 20.6%，P=.418；2 年 OS：5.1%对 20.6%，P=.418）。此外，较低的输注 CD34 细胞剂量、女性到男性移植和急性髓细胞白血病与复发和死亡风险增加显著相关。这项研究表明，在患者肿瘤负荷较低时，PT/Cy-haplo 通过供者 KIR2DS1 发挥移植物抗白血病/肿瘤效应。值得在建立 PT/Cy-haplo 的最佳供者选择标准时，检查供者 KIR 基因分型和疾病状态评估的纳入情况。
