Hematology Department, State Key Laboratory of Trauma, Burns and Combined Injury, Xinqiao Hospital of Army Medical University, Chongqing, China.
Shigatse Branch, Xinqiao Hospital, Army Medical University (Third Military Medical University), Shigatse, China.
Chemotherapy. 2019;64(2):81-93. doi: 10.1159/000501061. Epub 2019 Aug 7.
With the advent of tyrosine kinase inhibitors (TKIs), the treatment of Philadelphia chromosome-positive (Ph+) acute lymphoblastic leukemia (ALL) has entered a new era. The efficacy of TKIs compared with other ALL treatment options is emphasized by a rapid increase in the number of TKI clinical trials. Subsequently, the use of traditional approaches, such as combined chemotherapy and even allogeneic hematopoietic stem cell transplantation (allo-HSCT), for the treatment of ALL is being challenged in the clinic. In light of the increased use of TKIs in the clinic, several questions have been raised. First, is it necessary to use intensive chemotherapy during the induction course of therapy to achieve a minimal residual disease (MRD)-negative status? Must a patient reach a complete molecular response/major molecular response before receiving allo-HSCT? Does MRD status affect long-term survival after allo-HSCT? Is auto-HSCT an appropriate alternative for allo-HSCT in those Ph+ ALL patients who lack suitable donors? Here, we review the recent literature in an attempt to summarize the current status of TKI usage in the clinic, including several new therapeutic approaches, provide answers for the above questions, and speculate on the future direction of TKI utilization for the treatment of Ph+ ALL patients.
随着酪氨酸激酶抑制剂(TKI)的出现,费城染色体阳性(Ph+)急性淋巴细胞白血病(ALL)的治疗进入了一个新时代。TKI 的疗效优于其他 ALL 治疗选择,这体现在 TKI 临床试验的数量迅速增加。随后,传统方法(如联合化疗甚至异基因造血干细胞移植(allo-HSCT))在临床上治疗 ALL 的地位受到了挑战。鉴于 TKI 在临床上的广泛应用,提出了几个问题。首先,在治疗的诱导过程中是否有必要使用强化化疗以达到微小残留病(MRD)阴性状态?患者在接受 allo-HSCT 之前是否必须达到完全分子缓解/主要分子缓解?MRD 状态是否影响 allo-HSCT 后的长期生存?对于缺乏合适供体的 Ph+ ALL 患者,自体-HSCT 是否是 allo-HSCT 的合适替代方法?在这里,我们回顾了最近的文献,试图总结 TKI 在临床上的应用现状,包括一些新的治疗方法,为上述问题提供答案,并推测 TKI 治疗 Ph+ ALL 患者的未来方向。