The myelodysplastic syndrome (MDS) is considered to be a heterogeneous myeloid malignancy with a common origin in the hematopoietic stem cell compartment, generally divided into lower and higher risk. While treatment goal for lower risk MDS (LR-MDS) is to decrease transfusion burden and transformation into acute leukemia major aim for high risk MDS is to prolong survival and ultimately cure. While novel agents such as luspatercept or imetelstat have recently been approved as new treatment options for LR-MDS, hypomethylating agents (HMA) remain currently the only approved non-transplant option for HR-MDS and is the standard of care for non-transplant-eligible patients. Combinations with other drugs as first-line treatment has to date not proven more efficacious than monotherapy in HR-MDS, and outcome after HMA failure is poor. The only potential cure and standard of care for eligible patients is allogeneic stem cell transplantation (HSCT) and even if the number of transplanted - especially older - MDS patients increased over time due to a better management and donor availability the majority of MDS patients will not be eligible for this curative approach. Current challenges encompass to decrease the relapse risk, the main cause of HSCT failure. This review will summarize current knowledge of options of transplant- and non-transplant treatment approaches for these patients and demonstrate the unmet clinical need for more effective therapies.

中文翻译：

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高危骨髓增生异常综合征的治疗。


骨髓增生异常综合征 （MDS） 被认为是一种异质性髓系恶性肿瘤，共同起源于造血干细胞区室，通常分为低危和高危。虽然低危 MDS （LR-MDS） 的治疗目标是减少输血负担和转变为急性白血病，但高危 MDS 的主要目标是延长生存期并最终治愈。虽然 luspatercept 或 imetelstat 等新型药物最近被批准作为 LR-MDS 的新治疗选择，但低甲基化剂 （HMA） 仍然是目前唯一批准的 HR-MDS 非移植选择，并且是不符合移植条件的患者的标准护理。迄今为止，与其他药物联合作为一线治疗尚未证明比单药治疗 HR-MDS 更有效，并且 HMA 失败后的预后很差。符合条件的患者唯一可能的治愈和护理标准是同种异体干细胞移植 （HSCT），即使由于更好的管理和供体可用性，移植的 - 尤其是老年 - MDS 患者的数量随着时间的推移而增加，大多数 MDS 患者将不符合这种治疗方法。当前的挑战包括降低复发风险，这是 HSCT 失败的主要原因。本综述将总结目前对这些患者移植和非移植治疗方法选择的认识，并证明对更有效疗法的未满足临床需求。