McMahon Christine M, Luger Selina M
Division of Hematology and Oncology, Department of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, 19104, USA.
Perelman Center for Advanced Medicine, 12th Floor South Extension, 3400 Civic Center Blvd, Philadelphia, PA, 19104, USA.
Curr Hematol Malig Rep. 2019 Apr;14(2):83-93. doi: 10.1007/s11899-019-00501-3.
Patients with relapsed T cell acute lymphoblastic leukemia (T-ALL) have limited therapeutic options and a poor prognosis. Although a variety of salvage chemotherapy regimens may be used, response rates are unsatisfactory. This article summarizes current approaches and promising emerging strategies for the treatment of relapsed T-ALL.
Although nelarabine is the only agent approved specifically for T-ALL, recent studies have identified a variety of genetic alterations and signaling pathways that are critical in its pathogenesis. Based on these findings, a number of small-molecule inhibitors and other targeted therapies are being studied for relapsed T-ALL, including gamma-secretase inhibitors, BCL-2 inhibitors, cyclin-dependent kinase inhibitors, and mTOR inhibitors. In addition, pre-clinical studies of chimeric antigen receptor T cells targeting CD5 and CD7 as well as the monoclonal antibody daratumumab have shown promising results for T-ALL. Relapsed T-ALL currently remains challenging to treat, but recent pre-clinical studies of targeted and immunotherapeutic agents have shown encouraging results. A number of clinical trials investigating these approaches for T-ALL are currently underway.
复发的T细胞急性淋巴细胞白血病（T-ALL）患者的治疗选择有限且预后较差。尽管可以使用多种挽救性化疗方案，但缓解率并不理想。本文总结了治疗复发T-ALL的当前方法和有前景的新兴策略。
尽管奈拉滨是唯一专门批准用于T-ALL的药物，但最近的研究已经确定了多种在其发病机制中起关键作用的基因改变和信号通路。基于这些发现，正在对多种小分子抑制剂和其他靶向疗法进行复发T-ALL的研究，包括γ-分泌酶抑制剂、BCL-2抑制剂、细胞周期蛋白依赖性激酶抑制剂和mTOR抑制剂。此外，针对CD5和CD7的嵌合抗原受体T细胞以及单克隆抗体达雷妥尤单抗的临床前研究已显示出对T-ALL有前景的结果。复发T-ALL目前仍然难以治疗，但最近靶向和免疫治疗药物的临床前研究已显示出令人鼓舞的结果。目前正在进行多项针对这些T-ALL治疗方法的临床试验。
