Hrabovský Š, Folber F, Doubek M
Klin Onkol. 2019 Spring;32(2):90-96. doi: 10.14735/amko201990.
New diagnostics and treatments, including the use of new drugs, have advanced considerably the treatment of acute lymphoplastic leukemia (ALL) in the past few years. Monoclonal antibodies and immunoconjugates targeting antigens CD19 and CD22 show greater efficacy and more favourable toxicity profiles than standard salvage chemotherapeutic protocols. Two of these drugs - blinatumomab and inotuzumab ozogamicin - have already made their way into clinical practice. Ponatinib and other new generation tyrosine kinase inhibitors allow dose reduction of intensive cytostatic regimens in Ph-positive ALL patients and slowly start to overshadow the importance of allogeneic hematopoietic cell transplants. For the time being, their use is reserved for relapsed/refractory ALL, but they are already available as a first line therapy in clinical trials. An entirely new group of living drugs is emerging for the treatment of ALL - chimeric antigen receptor T-cells produced by genetic modification of native human cells. Chimeric antigen receptor T-cells can be looked upon as in vitro trained professional blast killers. They show an efficacy never seen before for the treatment of relapsed/refractory ALL. On the other hand, this treatment still presents significant risks, mainly due to cytokine release syndrome. Ruxolitinib, mTOR inhibitors, bortezomib, and other drugs for targeted treatment of ALL are currently being evaluated in clinical trials.
The article focuses on current options and news in the field of relapsed and refractory ALL treatment. This work was created at Masaryk University as part of the project “New Approaches in Research, Diagnostics and Therapy of Hematological Malignancies VI”, number MUNI/A/1105/2018, supported by Czech Ministry of Education, Youth and Sports in 2019. The Editorial Board declares that the manuscript met the ICMJE recommendation for biomedical papers. Submitted: 28. 8. 2018 Accepted: 10. 1. 2019.
在过去几年中，包括使用新药在内的新诊断方法和治疗手段极大地推动了急性淋巴细胞白血病（ALL）的治疗。与标准挽救性化疗方案相比，靶向抗原CD19和CD22的单克隆抗体及免疫偶联物显示出更高的疗效和更良好的毒性特征。其中两种药物——博纳吐单抗和奥英妥珠单抗——已进入临床实践。普纳替尼和其他新一代酪氨酸激酶抑制剂使得Ph阳性ALL患者强化细胞毒性治疗方案的剂量得以降低，并逐渐开始使异基因造血细胞移植的重要性黯然失色。目前，它们仅用于复发/难治性ALL，但在临床试验中已作为一线治疗药物可用。一种全新的活性药物类别正在兴起用于ALL的治疗——通过对天然人类细胞进行基因改造而产生的嵌合抗原受体T细胞。嵌合抗原受体T细胞可被视为体外训练的专业原始细胞杀手。它们在治疗复发/难治性ALL方面显示出前所未有的疗效。另一方面，这种治疗仍存在重大风险，主要是由于细胞因子释放综合征。芦可替尼、mTOR抑制剂、硼替佐米和其他用于ALL靶向治疗的药物目前正在临床试验中进行评估。
本文重点关注复发和难治性ALL治疗领域的当前选择和新进展。这项工作是在马萨里克大学开展的，是“血液系统恶性肿瘤研究、诊断和治疗的新方法VI”项目（编号MUNI/A/1105/2018）的一部分，由捷克教育、青年和体育部于2019年资助。编辑委员会声明该手稿符合ICMJE对生物医学论文的建议。提交日期：2018年8月28日。接受日期：2019年1月10日。
