Although killer Ig-like receptor ligands (KIR-L) mismatch has been associated with alloreactive natural killer cell activity and potent graft-versus-leukemia (GVL) effect among adults with acute myeloid leukemia (AML), its role among children with AML receiving cord blood transplantation (CBT) has not been determined. We conducted a retrospective study using a nationwide registry of the Japanese Society for Transplantation and Cellular Therapy. Patients who were diagnosed with de novo non-M3 AML and who underwent their first CBT in remission between 2000 and 2021 at under 16 years old were included. A total of 299 patients were included; 238 patients were in the KIR-L match group, and 61 patients were in the KIR-L mismatch group. The cumulative incidence rates of neutrophil recovery, platelet engraftment, and acute/chronic graft-versus-host disease did not differ significantly between the groups. The 5-year event-free survival (EFS) rate was 69.8% in the KIR-L match group and 74.0% in the KIR-L mismatch group (p = 0.490). Stratification by CD34 + cell dose into four groups revealed a significant correlation between CD34 + cell dose and EFS in the KIR-L mismatch group (p = 0.006) but not in the KIR-L match group (p = 0.325). According to our multivariate analysis, KIR-L mismatch with a high CD34 + cell dose (≥ median dose) was identified as an independent favorable prognostic factor for EFS (hazard ratio = 0.19, p = 0.029) and for the cumulative incidence of relapse (hazard ratio = 0.09, p = 0.021). Our results suggested that higher CD34 + cell doses are crucial for achieving a potent GVL effect in the context of KIR-L-mismatched CBT.

中文翻译：

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较高的 CD34 + 细胞剂量与儿童急性髓性白血病 KIR 配体错配脐带血移植后更好的无事件生存率相关


尽管杀伤性 Ig 样受体配体 （KIR-L） 错配与急性髓性白血病 （AML） 成人中的同种异体反应性自然杀伤细胞活性和有效的移植物抗白血病 （GVL） 效应有关，但其在接受脐带血移植 （CBT） 的 AML 儿童中的作用尚未确定。我们使用日本移植和细胞治疗学会的全国登记处进行了一项回顾性研究。包括被诊断患有新发非 M3 AML 并在 2000 年至 2021 年期间在 16 岁以下接受首次 CBT 缓解的患者。共纳入 299 例患者;238 例患者为 KIR-L 匹配组，61 例患者为 KIR-L 错配组。中性粒细胞恢复、血小板植入和急性/慢性移植物抗宿主病的累积发生率在两组间无显著差异。KIR-L 匹配组的 5 年无事件生存率 （EFS） 为 69.8%，KIR-L 错配组为 74.0% （p = 0.490）。按 CD34 + 细胞剂量分为四组显示，在 KIR-L 错配组 （p = 0.006） 中，CD34 + 细胞剂量与 EFS 之间存在显着相关性，但在 KIR-L 匹配组中没有相关性 （p = 0.325）。根据我们的多变量分析，KIR-L 与高 CD34 + 细胞剂量 （≥ 中位剂量） 的不匹配被确定为 EFS （风险比 = 0.19，p = 0.029） 和累积复发发生率 （风险比 = 0.09，p = 0.021） 的独立有利预后因素。我们的结果表明，在 KIR-L 不匹配的 CBT 的情况下，更高的 CD34 + 细胞剂量对于实现有效的 GVL 效应至关重要。