骨髓增生异常综合征合并血小板减少症的原因及治疗策略

Mechanisms and therapies of thrombocytopenia in myelodysplastic syndrome

骨髓增生异常综合征(MDS)是一类骨髓衰竭性疾病。血小板减少症是MDS患者常见的致死原因之一,其占总MDS患者的比例约为37%～67%,并且是MDS的一项独立不良预后因素,与急性髓系白血病(AML)进展高风险和总体生存期短相关,并且限制去甲基化药物和免疫调节剂等治疗药物的使用。MDS合并血小板减少症的发病机制复杂,涉及巨核细胞分化受阻、凋亡亢进和血小板破坏增多等多方面因素。目前MDS合并血小板减少的标准治疗方法是血小板输注。新型血小板生成素(TPO)受体激动剂罗米司亭和艾曲泊帕在治疗MDS合并血小板减少症方面有一定的疗效,可有效减少出血事件和血小板输注量,并且与免疫调节剂和去甲基化药物联用可增加临床获益。多项临床试验正在研究新型TPO受体激动剂的安全性和疗效,研究结果将进一步指导MDS合并血小板减少症的治疗。

Myelodysplastic syndromes(MDS)is a kind of bone marrow failure disease.Thrombocytopenia in patients with MDS is a frequent causes of mortality in MDS with 37%to 67%incidence.Thrombocytopenia in MDS is an independent factor predicting worse prognosis associated with increased risk of acute leukemic transformation(AML)and reduces overall survival.In addition,thrombocytopenia in MDS limits the therapeutic efficacy of disease-modifying therapies,such as azacitidine or lenalidomide.Mechanisms of thrombocytopenia in MDS are complicated,involving suppression of megakaryocytic differentiation,enhanced apoptosis,and increased platelet destruction.Platelet transfusion is still the standard treatment option for MDS combined with thrombocytopenia.Recently,novel thrombopoietin(TPO)receptor agonists have showed curative effect in MDS patients in many clinical trials,including reducing bleeding events,decreasing dependency on platelet transfusions and increasing clinical benefits of disease-modifying therapies.Several clinical trials are ongoing to assess the efficacy and safety of novel TPO receptor agonists;the results would further help guide treatment for thrombocytopenia in MDS.