Raetz Elizabeth A, Teachey David T
Department of Pediatrics and Huntsman Cancer Institute, University of Utah, Salt Lake City, UT.
Department of Pediatrics, Children's Hospital of Philadelphia, University of Pennsylvania, Philadelphia, PA.
Hematology Am Soc Hematol Educ Program. 2016 Dec 2;2016(1):580-588. doi: 10.1182/asheducation-2016.1.580.
T-cell acute lymphoblastic leukemia (T-ALL) is biologically distinct from its B lymphoblastic (B-ALL) counterpart and shows different kinetic patterns of disease response. Although very similar regimens are used to treat T-ALL and B-ALL, distinctions in response to different elements of therapy have been observed. Similar to B-ALL, the key prognostic determinant in T-ALL is minimal residual disease (MRD) response. Unlike B-ALL, other factors including age, white blood cell count at diagnosis, and genetics of the ALL blasts are not independently prognostic when MRD response is included. Recent insights into T-ALL biology, using modern genomic techniques, have identified a number of recurrent lesions that can be grouped into several targetable pathways, including Notch, Jak/Stat, PI3K/Akt/mTOR, and MAPK. With contemporary chemotherapy, outcomes for de novo T-ALL have steadily improved and now approach those observed in B-ALL, with approximately 85% 5-year event-free survival. Unfortunately, salvage has remained poor, with less than 25% event-free and overall survival rates for relapsed disease. Thus, current efforts are focused on preventing relapse by augmenting therapy for high-risk patients, sparing toxicity in favorable subsets and developing new approaches for the treatment of recurrent disease.
T细胞急性淋巴细胞白血病(T-ALL)在生物学上与其B淋巴细胞白血病(B-ALL)对应物不同,并且显示出不同的疾病反应动力学模式。尽管用于治疗T-ALL和B-ALL的方案非常相似,但已观察到对不同治疗要素的反应存在差异。与B-ALL相似,T-ALL的关键预后决定因素是微小残留病(MRD)反应。与B-ALL不同,当纳入MRD反应时,包括年龄、诊断时白细胞计数和ALL原始细胞遗传学在内的其他因素并不能独立预测预后。利用现代基因组技术对T-ALL生物学的最新见解,已经确定了一些复发性病变,这些病变可分为几个可靶向的途径,包括Notch、Jak/Stat、PI3K/Akt/mTOR和MAPK。随着当代化疗的应用,初治T-ALL的预后稳步改善,目前已接近B-ALL的预后,5年无事件生存率约为85%。不幸的是,挽救治疗效果仍然很差,复发疾病的无事件生存率和总生存率均低于25%。因此,目前的努力集中在通过加强对高危患者的治疗来预防复发,在预后良好的亚组中避免毒性,并开发治疗复发性疾病的新方法。