亚砷酸治疗急性早幼粒细胞白血病的研究进展

Progress in long-term survival of patients with acute promyelocytic leukemia treated with arsenite acid

急性早幼粒细胞白血病(acute promyelocytic leukemia,APL)作为急性髓系白血病(acute myeloid leukemia,AML)的独特亚型,以异常的早幼粒细胞增多、危及生命的出血和t(15;17)染色体易位为特征,曾被认为是最凶险的白血病。亚砷酸(application of arsenite acid,ATO)的应用大大提高了该病的治疗效果,显著改善了患者的预后,大量患者长期生存。本文综述相关研究发现:ATO在肝脏中由无机砷(iSA)转化为甲基化砷,通过多种分子机制促进早幼粒细胞分化、凋亡。在任何年龄阶段,无论白细胞是否>10×10^(9)/L,ATO联合其他药物治疗APL,都可以减少化疗药物的剂量,降低患者的累积复发率(CIR),减少患者的死亡率。单药ATO可高效安全治疗APL。对于复发APL,一部分相关研究支持继续ATO+维甲酸(ATO+retinoic acid,ATRA)或ATO+ATRA+化疗的治疗,一部分研究支持移植前给予ATO治疗可显著改善患者的整体预后和长期生存,观点尚未统一,有待进一步研究。ATO常见的毒副作用主要为分化综合征(differentiation syndrome,DS)、心脏毒性及肝毒性,明显比化疗药物造成的毒副作用轻微。

Acute promyelocytic leukemia(APL),a unique subtype of acute myeloid leukemia(AML),is characterized by abnormal promyelocytes,life-threatening bleeding,and t(15;17)Chromosomal translocation,which was once considered the most dangerous leukemia.The application of arsenite acid(ATO)has greatly improved the therapeutic effect of the disease,significantly improved the prognosis of patients and a large number of patients with long-term survival.In this review,arsenite is converted from inorganic arsenic to methylated arsenic in liver,which promote promyelocyte differentiation and apoptosis through various molecular mechanisms.Regardless of white blood cells>10×10^(9)/L at any age,ATO combined with other drugs in the treatment of APL can reduce the dose of chemotherapy drugs,reduce the cumulative recurrence rate of patients(CIR),and reduce the mortality of patients.Single-agent ATO has high efficiency and safety in the treatment of this disease.For relapsed APL,a number of studies support continued ATO+retinoic acid(ATRA)or ATO+ATRA+chemotherapy,and a number of studies support that introduction of arsenite before transplantation,which significantly improves overall prognosis and long-term survival.The common toxic and side effects of ATO mainly include differentiation syndrome(DS),cardiotoxicity and hepatotoxicity,which are obviously slighter than those caused by chemotherapy drugs.