Yokoyama Yasuhisa
Department of Hematology, Faculty of Medicine, University of Tsukuba.
Rinsho Ketsueki. 2020;61(9):1166-1173. doi: 10.11406/rinketsu.61.1166.
All-trans retinoic acid (ATRA) in combination with chemotherapies had been the standard therapy for newly diagnosed acute promyelocytic leukemia (APL). In Japan, APL204 study using ATRA+chemotherapy showed favorable outcomes, in which 7-year event-free and overall survival rates were 79% and 87%, respectively. Recently, a combination of ATRA and arsenic trioxide (ATO) has emerged as a promising therapy for newly diagnosed APL. Specifically, for patients with standard-risk APL with an initial white blood cell count (WBC) of <10,000/µl, two randomized controlled trials showed superior outcomes using ATRA+ATO to ATRA+chemotherapy, with long-term survival rates above 90%. Now ATRA+ATO is considered as an established standard therapy for newly diagnosed patients with standard-risk APL. Some prospective studies have also showed the efficacies of ATRA+ATO in patients with high-risk APL with an initial WBC of >10,000/µl although the administration of gemtuzumab ozogamicin or idarubicin was required in addition to ATRA+ATO during induction therapy. This review briefly summarizes the findings of ATRA+chemotherapy, focusing on the APL204 study, and introduces trials of ATRA+ATO for newly diagnosed APL. Furthermore, it describes the management of complications, including disseminated coagulation and differentiation syndrome.
全反式维甲酸(ATRA)联合化疗一直是新诊断急性早幼粒细胞白血病(APL)的标准治疗方法。在日本,使用ATRA+化疗的APL204研究显示出良好的结果,其中7年无事件生存率和总生存率分别为79%和87%。最近,ATRA与三氧化二砷(ATO)的联合应用已成为新诊断APL的一种有前景的治疗方法。具体而言,对于初始白细胞计数(WBC)<10,000/µl的标准风险APL患者,两项随机对照试验显示,使用ATRA+ATO比ATRA+化疗的结果更优,长期生存率超过90%。现在,ATRA+ATO被认为是新诊断的标准风险APL患者的既定标准治疗方法。一些前瞻性研究也显示了ATRA+ATO对初始WBC>10,000/µl的高危APL患者有效,尽管在诱导治疗期间除了ATRA+ATO外还需要给予吉妥珠单抗奥唑米星或伊达比星。本综述简要总结了ATRA+化疗的研究结果,重点介绍了APL204研究,并介绍了新诊断APL的ATRA+ATO试验。此外,还描述了包括弥散性凝血和分化综合征在内的并发症的管理。