骨髓增生异常综合征患者低甲基化治疗失败后的治疗选择  

Options for patients with myelodysplastic syndromes after the treatment failure of hypomethylating agent

作　　者：唐旭东[1] 张路[3] 杨秀鹏[1] 唐玉凤[2] 王德秀 

机构地区：[1]中国中医科学院西苑医院血液科,北京100091 [2]中国中医科学院西苑医院检验科,北京100091 [3]北京中医药大学管理学院综合办公室,100029 [4]北京中医药大学研究生院,100029

出　　处：《白血病．淋巴瘤》2017年第10期577-581,共5页Journal of Leukemia & Lymphoma

基　　金：国家中医药管理局中医药行业科研专项（201507001-13）;国家自然科学基金青年基金（81303127）;国家自然科学基金面上项目（81673819）;中国博士后科学基金（2014M551002）

摘　　要：骨髓增生异常综合征（MDS）的主要治疗包括支持治疗（如输血、集落刺激因子、螯合铁等）和靶向药物（5．氮杂胞苷、地西他滨、来那度胺）。如果患者对以上药物无效，则缺乏有效的治疗方法。治疗失败后，目前努力的方向是继续调整并优化去甲基化药物（HMT）方案，改善药物制剂[口服制剂和（或）新制剂]，根据突变筛选患者，提高HMT治疗MDS的针对性和有效性。此外，正在进行的研究重点是确定用来作为HMT治疗失败后挽救MDS患者的独特药物。如rigoserlib最有可能使特定人群[原发性难治性和国际预后评分系统（IPSS）评分为高危的患者]受益。鉴于实体肿瘤免疫逃逸的重要进展，程序性死亡受体1（PD-1）和PD-1抑制剂单剂可在早期治疗和复发时联合HMT治疗MDS。对于那些有特定靶向突变基因的少数民族患者，有替代药物（IDHl／2）是非常有希望的。骨髓移植是治愈MDS的唯一方法，但因MDS进展时大多患者都年老体弱，所以移植的可行性不大。The treatment of patients with myelodysplastie syndromes （MDS） has included primarily supportive care （blood transfusions, colony stimulating agents, iron chelation, etc.） and new drugs, including 5-azacytidine, deoxyazacytidine, and lenalidomide. For those who are no longer benefiting from these agents, there is nearly nothing to do with effective therapies. When those drugs are ineffective, what the doctors could do is optimizing the delivery of hypomethylating agents （HMT） by dosing appropriately, sequencing appropriately, and using thoughtful combinations; as well as improving drug formulations （oral formulations and/or novel formulations） and working toward better selection of patients for best upfront mutation-directed therapy. Hopefully, the drug targeting and patient selection for optimal HMT treatment of MDS will be improved. Furthermore, ongoing research is focused on identifying unique agents to rescue MDS patients who have progressed despite HMT. Agents such as rigosertib are now focused on its application in specific MDS populations who might most likely benefit from this therapeutic approach [primary refractory and high-risk international prognostic scoring system （IPSS） patients]. Doctors eagerly await results of single-agent programmed death 1 （PD-1） and its inhibitors, or combination with HMT to the upfront and relapsed MDS setting. For the minority of patients who have specific targetable mutations, the selective agents （IDHI/2） are highly promising. Bone marrow transplantation remains the only offer for cure, but is depressingly unrealistic given the majority of the elderly and frail patients at the time of MDS progression.

关 键 词：骨髓增生异常综合征 去甲基化药物 治疗失败 

分 类 号：R551.3[医药卫生—血液循环系统疾病]