Yu Guopan, Chen Fang, Yin Changxin, Liu Qifa, Sun Jing, Xuan Li, Fan Zhiping, Wang Qiang, Liu Xiaoli, Jiang Qianli, Xu Dan
Department of Hematology, Nanfang Hospital, Southern Medical University, Guangzhou, China.
Oncotarget. 2017 Oct 31;8(63):107022-107032. doi: 10.18632/oncotarget.22206. eCollection 2017 Dec 5.
The treatment of Ph-positive acute lymphoblastic leukemia (Ph+ ALL) has entranced tyrosine kinase inhibitors (TKIs) era. Currently both imatinib and dasatinib are registered as the front-line treatment for Ph+ ALL, and the other 2-generation TKIs are suggested as an alternative for those who failed the first-line treatment. However, it remains unclear who could benefit from the 2-generation TKIs as the first-line treatment for Ph+ ALL. In this study we compared the efficacy and safety of the 1 and 2-generation TKIs in the front-line treatment of Ph+ ALL and found a trend toward better disease-free survival (DFS) in the 2-generation TKIs group, though no significant difference in early response and long-term survival between the two groups. Furthermore, subgroup analysis showed that if allogeneic hematopoietic stem cell transplantation (allo-HSCT) was incorporated as consolidation, the 2-generation TKIs benefited patients with better DFS and overall survival (OS). The two generation TKIs were well tolerated. Higher incidence of acquiring T315I mutation was observed in the patients relapsed on the 2-generation TKIs. These findings suggested front-line treatment of Ph+ ALL with the 2-generation TKIs might benefit patients with better survival when allo-HSCT was incorporated as consolidation therapy; meanwhile, the higher incidence of T315I mutation in patients relapsed on the 2-generation TKIs deserved further attention.
Ph 阳性急性淋巴细胞白血病（Ph+ ALL）的治疗已进入酪氨酸激酶抑制剂（TKI）时代。目前，伊马替尼和达沙替尼均已注册为 Ph+ ALL 的一线治疗药物，其他二代 TKI 被建议作为一线治疗失败患者的替代药物。然而，目前尚不清楚谁能从二代 TKI 作为 Ph+ ALL 的一线治疗中获益。在本研究中，我们比较了一代和二代 TKI 在 Ph+ ALL 一线治疗中的疗效和安全性，发现二代 TKI 组的无病生存期（DFS）有改善趋势，尽管两组在早期反应和长期生存方面无显著差异。此外，亚组分析显示，如果将异基因造血干细胞移植（allo-HSCT）作为巩固治疗，二代 TKI 可使患者获得更好的 DFS 和总生存期（OS）。二代 TKI 的耐受性良好。在二代 TKI 治疗后复发的患者中观察到 T315I 突变的发生率更高。这些发现表明，当将 allo-HSCT 作为巩固治疗时，二代 TKI 一线治疗 Ph+ ALL 可能使患者获得更好的生存；同时，二代 TKI 治疗后复发患者中 T315I 突变的较高发生率值得进一步关注。
