HLA Polymorphisms Are Associated with Treatment-Free Remission Following Discontinuation of Tyrosine Kinase Inhibitors in Chronic Myeloid Leukemia
HLA Polymorphisms Are Associated with Treatment-Free Remission Following Discontinuation of Tyrosine Kinase Inhibitors in Chronic Myeloid Leukemia
复制标题
HLA 多态性与慢性粒细胞白血病停用酪氨酸激酶抑制剂后的无治疗缓解相关
DOI：
10.1158/1535-7163.mct-20-0336
复制
发表时间：
2021
影响因子：
5.7
通讯作者：
Kimura S
中科院分区：
文献类型：
--
作者：
Ureshino H;Shindo T;Tanaka H;Saji H;Kimura S
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。虽然以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。我们先前报道了杀伤免疫球蛋白样受体（KIR）和人类白细胞抗原（HLA）的等位基因多态性与CML-CP患者实现深度分子应答（DMR）相关。在此，我们研究了停用酪氨酸激酶抑制剂（TKI）的患者TFR与KIR和HLA多态性之间的关系。76例患者入组，并如前所述研究其KIR和HLA多态性和自然杀伤（NK）细胞活化状态。总体而言，33例患者停用TKI，21/33例患者在1年时达到TFR [63.6%; 95%置信区间（CI），44.9%-77.5%]。多因素分析显示，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的患者比未达到DMR并停用TKI的患者表现出更高的NK细胞活化状态。相比之下，在达到TFR的患者和经历分子复发的患者之间，NK细胞活化状态没有显著差异。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。
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 ofKIRsandHLAsin patients who discontinued tyrosine kinase inhibitors (TKI). Seventy-six patients were enrolled, and theirKIRandHLApolymorphisms 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) andHLA-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.