Treatment-free remission (TFR) is one of the therapeutic goals for patients with chronic phase chronic myeloid leukemia (CML-CP). Although previous reports indicated that antitumor immunity contributes to TFR, its determinants are still unclear. We previously reported that allelic polymorphisms of killer immunoglobulin-like receptors (KIR) and human leukocyte antigens (HLA) are associated with achievement of deep molecular response (DMR) in patients with CML-CP. Here, we examined the association between TFR and polymorphisms of KIRs and HLAs in patients who discontinued tyrosine kinase inhibitors (TKI). Seventy-six patients were enrolled, and their KIR and HLA polymorphisms and natural killer (NK) cell activation status were investigated as previously described. Overall, 33 patients discontinued TKIs, and 21 of 33 achieved TFR [63.6%; 95% confidence interval (CI), 44.9%–77.5%] at 1 year. Multivariate analysis revealed that male sex (HR, 0.157; 95% CI, 0.031–0.804; P = 0.003) and HLA-A*02:01, *11:01, or *24:02 (HR, 6.386; 95% CI, 1.701–23.980; P = 0.006) were associated with TFR. Patients who achieved DMR and discontinued TKIs exhibited higher NK cell activation status than those who did not. By contrast, there were no significant differences in NK cell activation status between the patients who achieved TFR and those who experienced molecular relapse. These results suggest NK cell activation status contributes to achievement of DMR, whereas T-cell–mediated immunity contributes to TFR in patients with CML-CP.

中文翻译：

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HLA 多态性与慢性粒细胞白血病中酪氨酸激酶抑制剂停用后的无治疗缓解有关。

免治疗缓解（TFR）是慢性期慢性粒细胞白血病（CML-CP）患者的治疗目标之一。尽管先前的报道表明抗肿瘤免疫有助于 TFR，但其决定因素仍不清楚。我们之前报道过杀伤性免疫球蛋白样受体 (KIR) 和人类白细胞抗原 (HLA) 的等位基因多态性与 CML-CP 患者实现深度分子反应 (DMR) 相关。在这里，我们检查了停用酪氨酸激酶抑制剂 (TKI) 的患者的 TFR 与 KIR 和 HLA 多态性之间的关联。招募了 76 名患者，并如前所述研究了他们的 KIR 和 HLA 多态性和自然杀伤 (NK) 细胞活化状态。总体而言，33 名患者停用 TKI，33 名患者中有 21 名达到 TFR [63.6%; 95% 置信区间 (CI), 44.9%–77.5%] 在 1 年。多变量分析显示男性（HR，0.157；95% CI，0.031-0.804；P = 0.003）和 HLA-A*02:01、*11:01 或 *24:02（HR，6.386；95% CI , 1.701–23.980; P = 0.006) 与 TFR 相关。达到 DMR 并停用 TKI 的患者比没有达到 DMR 的患者表现出更高的 NK 细胞活化状态。相比之下，达到 TFR 的患者和经历分子复发的患者之间的 NK 细胞活化状态没有显着差异。这些结果表明 NK 细胞活化状态有助于实现 DMR，而 T 细胞介导的免疫有助于 CML-CP 患者的 TFR。386; 95% 置信区间，1.701–23.980；P = 0.006）与 TFR 相关。达到 DMR 并停用 TKI 的患者比没有达到 DMR 的患者表现出更高的 NK 细胞活化状态。相比之下，达到 TFR 的患者和经历分子复发的患者之间的 NK 细胞活化状态没有显着差异。这些结果表明 NK 细胞活化状态有助于实现 DMR，而 T 细胞介导的免疫有助于 CML-CP 患者的 TFR。386; 95% 置信区间，1.701–23.980；P = 0.006）与 TFR 相关。达到 DMR 并停用 TKI 的患者比没有达到 DMR 的患者表现出更高的 NK 细胞活化状态。相比之下，达到 TFR 的患者和经历分子复发的患者之间的 NK 细胞活化状态没有显着差异。这些结果表明 NK 细胞活化状态有助于实现 DMR，而 T 细胞介导的免疫有助于 CML-CP 患者的 TFR。