Imai Kiyotoshi
Department of Hematology, Sapporo Hokuyu Hospital.
Rinsho Ketsueki. 2017;58(10):1995-2003. doi: 10.11406/rinketsu.58.1995.
Most patients with adult acute lymphoblastic leukemia (ALL) undergo relapse, despite the achievement of complete remission with chemotherapy. Among patients with relapsed or refractory ALL, remission rates are 18-44% with the use of standard salvage chemotherapy, but the duration of remission is short. A major goal in this population is to induce remission with a sufficient duration to prepare for stem cell transplantation. The poor outcomes and lack of durable responses seen with conventional chemotherapy have led to the development of several novel agents, including clofarabine and nelarabine. Prior to the advent of tyrosine kinase inhibitors, patients with Ph-positive ALL treated with combination chemotherapy regimens were able to achieve high rates of complete response and long survival duration along with subsequent stem cell transplantation. A potent tyrosine kinase inhibitor ponatinib that is active against the T315I mutation is available. Novel monoclonal antibodies have been developed for the treatment of patients with Ph-negative ALL. Among patients with relapsed or refractory ALL, inotuzumab ozogamicin, blinatumomab, and CAR T-cell therapy have shown promising results. Follow-up is needed to further confirm their outcomes and toxicity profiles. Several clinical trials in this field are ongoing because of the lack of an established standard therapy.
大多数成人急性淋巴细胞白血病（ALL）患者尽管通过化疗实现了完全缓解，但仍会复发。在复发或难治性ALL患者中，使用标准挽救性化疗的缓解率为18% - 44%，但缓解持续时间较短。该人群的一个主要目标是诱导出足够长时间的缓解，为干细胞移植做准备。传统化疗效果不佳且缺乏持久反应，促使了包括氯法拉滨和奈拉滨在内的几种新型药物的研发。在酪氨酸激酶抑制剂出现之前，接受联合化疗方案治疗的Ph阳性ALL患者能够实现较高的完全缓解率和较长的生存期，并随后进行干细胞移植。有一种有效的酪氨酸激酶抑制剂波纳替尼，它对T315I突变有活性。已开发出新型单克隆抗体用于治疗Ph阴性ALL患者。在复发或难治性ALL患者中，吉妥珠单抗奥唑米星、博纳吐单抗和嵌合抗原受体（CAR）T细胞疗法已显示出有前景的结果。需要进行随访以进一步确认其疗效和毒性特征。由于缺乏既定的标准疗法，该领域正在进行多项临床试验。
