M.D. Anderson Cancer Center, Departments of Pharmacy and Leukemia , 1515 Holcombe Boulevard, Unit 428, Houston, TX 77030 , USA.
Expert Opin Emerg Drugs. 2014 Mar;19(1):37-50. doi: 10.1517/14728214.2014.872629. Epub 2013 Dec 20.
Acute lymphoblastic leukemia (ALL) is typically treated with complex multi-agent chemotherapy regimens over a prolonged time period. Long-term outcomes depend on the age of the patient and the biological characteristics of the leukemic cells. While pediatric patients achieve cure more often than adults, therapy can continue to be improved for all patients with this disease.
The current management strategy for ALL is reviewed. Recently, targeted therapies have been shown to improve survival in subsets of patients, most notably in those with Philadelphia chromosome-positive ALL or with leukemic cells that express the surface antigen CD20. Several innovative compounds are under investigation, and the most promising ones to date will be discussed.
The incorporation of monoclonal antibody therapy represents a targeted and powerful approach to the management of ALL. Bispecific T-cell engaging agents, such as blinatumomab, are able to facilitate immune-mediated killing of leukemia cells. Immunoconjugates (i.e., monoclonal antibodies linked to various cytotoxins) allow small doses of very potent chemotherapy to be delivered directly to a leukemia cell with hope of sparing normal tissue. As the genetic and molecular characterization of ALL is more completely understood, patients will receive treatment plans that are more individualized than previously possible.
急性淋巴细胞白血病(ALL)通常需要经过长时间的复杂多药物化疗方案治疗。长期预后取决于患者的年龄和白血病细胞的生物学特征。尽管儿科患者的治愈率通常高于成人,但所有此类疾病患者的治疗都可以继续得到改善。
本文回顾了 ALL 的当前治疗策略。最近,靶向治疗已被证明可改善某些患者的生存率,尤其是费城染色体阳性 ALL 患者或表达表面抗原 CD20 的白血病细胞患者。目前正在研究几种创新药物,本文将讨论迄今为止最有前途的药物。
单克隆抗体治疗的应用代表了针对 ALL 治疗的一种靶向且强大的方法。双特异性 T 细胞衔接剂,如blinatumomab,能够促进免疫介导的白血病细胞杀伤。免疫偶联物(即与各种细胞毒素连接的单克隆抗体)可将小剂量非常有效的化疗药物直接递送至白血病细胞,以期避免正常组织受到损害。随着对 ALL 的基因和分子特征的更全面了解,患者将接受比以往更加个体化的治疗计划。