Leukemia Program, Department of Hematologic Oncology and Blood Disorders, Cleveland Clinic Taussig Cancer Institute, Desk R35, 9500 Euclid Avenue, Cleveland, OH 44195, USA.
Int J Hematol. 2012 Jan;95(1):26-33. doi: 10.1007/s12185-011-0987-4. Epub 2012 Jan 6.
The myelodysplastic syndromes (MDS) consist of an array of clonal hematological malignancies resulting from disorders of pluripotent hematopoietic stem cells. MDS is associated with a poor overall prognosis and patients are categorized as higher risk and lower risk on the basis of the International Prognostic Scoring System. Currently, lenalidomide, azacitidine, and decitabine are the only three FDA-approved drugs for MDS. Traditional therapies for MDS involve the administration of single agents providing either supportive measures or disease-modifying effects directed to slowing progression to acute myeloid leukemia (AML) and improving survival. Recently, however, there has been increasing evidence suggesting that the combination of drugs with different mechanisms of action offers substantial benefit in the form of diminished side effects, improved overall survival, and delayed progression to AML. Multiple studies indicate that when compared with traditional monotherapies, combining various medications with non-overlapping mechanisms of action and toxicities may result in significant benefit for patients with MDS. A variety of combination therapies with growth factors, DNA methytransferase inhibitors, histone deacetylase inhibitors, and immunosuppressant treatments provide encouraging data indicating that the successful future of MDS treatment rests in the combination of multiple treatments modalities to achieve improved clinical outcomes.
骨髓增生异常综合征（MDS）是一组由多能造血干细胞紊乱引起的克隆性血液系统恶性肿瘤。MDS 预后不良，根据国际预后评分系统，患者被分为高危和低危。目前，来那度胺、阿扎胞苷和地西他滨是唯一三种获得 FDA 批准用于 MDS 的药物。MDS 的传统治疗方法包括使用单一药物，提供支持性措施或针对减缓向急性髓细胞白血病（AML）进展和改善生存的疾病修饰作用。然而，最近有越来越多的证据表明，具有不同作用机制的药物联合使用可减少副作用、提高总生存率和延迟向 AML 进展，从而带来实质性的益处。多项研究表明，与传统的单一疗法相比，联合使用具有不同作用机制和毒性的多种药物可能会为 MDS 患者带来显著的益处。多种联合治疗方案，包括生长因子、DNA 甲基转移酶抑制剂、组蛋白去乙酰化酶抑制剂和免疫抑制剂治疗，提供了令人鼓舞的数据，表明 MDS 治疗的未来在于联合多种治疗方式以实现改善的临床结果。
