Karolinska Institutet, Center for Hematology and Regenerative Medicine, Department of Medicine Huddinge, Karolinska University Hospital, Stockholm, Sweden.
Karolinska Institutet, Center for Hematology and Regenerative Medicine, Department of Medicine Huddinge, Karolinska University Hospital, Stockholm, Sweden
Haematologica. 2020 Jul;105(7):1765-1779. doi: 10.3324/haematol.2020.248955. Epub 2020 May 21.
The myelodysplastic syndromes (MDS) share their origin in the hematopoietic stem cell but have otherwise very heterogeneous biological and genetic characteristics. Clinical features are dominated by cytopenia and a substantial risk for progression to acute myeloid leukemia. According to the World Health Organization, MDS is defined by cytopenia, bone marrow dysplasia and certain karyotypic abnormalities. The understanding of disease pathogenesis has undergone major development with the implementation of next-generation sequencing and a closer integration of morphology, cytogenetics and molecular genetics is currently paving the way for improved classification and prognostication. True precision medicine is still in the future for MDS and the development of novel therapeutic compounds with a propensity to markedly change patients' outcome lags behind that for many other blood cancers. Treatment of higher-risk MDS is dominated by monotherapy with hypomethylating agents but novel combinations are currently being evaluated in clinical trials. Agents that stimulate erythropoiesis continue to be first-line treatment for the anemia of lower-risk MDS but luspatercept has shown promise as second-line therapy for sideroblastic MDS and lenalidomide is an established second-line treatment for del(5q) lower-risk MDS. The only potentially curative option for MDS is hematopoietic stem cell transplantation, until recently associated with a relatively high risk of transplant-related mortality and relapse. However, recent studies show increased cure rates due to better tools to target the malignant clone with less toxicity. This review provides a comprehensive overview of the current status of the clinical evaluation, biology and therapeutic interventions for this spectrum of disorders.
骨髓增生异常综合征（MDS）起源于造血干细胞，但具有非常异质的生物学和遗传学特征。临床特征主要表现为细胞减少症和向急性髓系白血病进展的高风险。根据世界卫生组织的定义，MDS 是由细胞减少症、骨髓发育不良和某些核型异常所定义的。随着下一代测序的实施以及形态学、细胞遗传学和分子遗传学的更紧密结合，疾病发病机制的理解已经取得了重大进展，目前正在为改进分类和预后铺平道路。真正的精准医学仍在未来，新型治疗化合物的开发具有显著改变患者预后的倾向，但与许多其他血液癌症相比，这一进展落后了。高危 MDS 的治疗主要采用低甲基化剂的单药治疗，但目前正在临床试验中评估新的联合治疗方案。刺激红细胞生成的药物仍然是低危 MDS 贫血的一线治疗药物，但 luspatercept 已显示出作为治疗铁粒幼细胞性 MDS 的二线治疗的潜力，lenalidomide 是治疗 del(5q)低危 MDS 的既定二线治疗药物。MDS 唯一有潜在治愈可能的方法是造血干细胞移植，直到最近，该方法与较高的移植相关死亡率和复发率相关。然而，最近的研究表明，由于有更好的工具来靶向恶性克隆，毒性更小，治愈率有所提高。本综述全面概述了该疾病谱的临床评估、生物学和治疗干预的现状。
