Division of Hematology, Mayo Clinic Rochester, Minnesota.
Am J Hematol. 2016 Jan;91(1):76-89. doi: 10.1002/ajh.24253.
Myelodysplastic syndromes (MDS) are a heterogeneous group of clonal stem cell disorders with an inherent tendency for leukemic transformation. Diagnosis is currently based on the presence of peripheral blood cytopenias, peripheral blood and bone marrow dysplasia/blasts, and clonal cytogenetic abnormalities. With the advent of next generation sequencing, recurrent somatic mutations in genes involved in epigenetic regulation (TET2, ASXL1, EZH2, DNMT3A, IDH1/2), RNA splicing (SF3B1, SRSF2, U2AF1, ZRSR2), DNA damage response (TP53), transcriptional regulation (RUNX1, BCOR, ETV6) and signal transduction (CBL, NRAS, JAK2) have been identified in MDS. Conventional prognostication is by the revised International prognostic scoring system (IPSS-R) with additional adverse prognosis conferred by presence of ASXL1, EZH2, or TP53 mutations. Currently Food and Drug administration (FDA)-approved drugs for the treatment of MDS are not curative and their effect on survival is limited; they include the hypomethylating agents (HMA) azacitidine and decitabine and lenalidomide for MDS with isolated del(5q). To date, allogeneic stem cell transplant (ASCT) remains the only treatment option for possible cure. Given the current lack of drugs with convincing evidence of favorable effect on survival, we consider ASCT as the treatment of choice for most patients with symptomatic disease, and especially for those with high-risk disease. For nontransplant candidates, participation in clinical trials is preferred over conventional therapy. There is not one right way of treatment for patients who are not candidates for either ASCT or clinical trials and palliative drugs of choice depend on the clinical problem, such as symptomatic anemia (ESAs, danazol, HMA), thrombocytopenia (HMA), or neutropenia (myeloid growth factors). Conversely, there is no controlled evidence to support the use of iron chelating agents in MDS. Going forward, we believe it is time to incorporate mutation information in clinically derived prognostic models in MDS and encourage development of novel drugs with disease-modifying activity.
骨髓增生异常综合征（MDS）是一组异质性克隆性干细胞疾病，具有向白血病转化的固有倾向。目前的诊断基于外周血血细胞减少、外周血和骨髓发育不良/原始细胞增多以及克隆细胞遗传学异常。随着下一代测序技术的出现，参与表观遗传调控（TET2、ASXL1、EZH2、DNMT3A、IDH1/2）、RNA 剪接（SF3B1、SRSF2、U2AF1、ZRSR2）、DNA 损伤反应（TP53）、转录调节（RUNX1、BCOR、ETV6）和信号转导（CBL、NRAS、JAK2）的基因中反复出现的体细胞突变已在 MDS 中得到鉴定。传统的预后评估是通过修订后的国际预后评分系统（IPSS-R），ASXL1、EZH2 或 TP53 突变的存在赋予了额外的不良预后。目前，美国食品和药物管理局（FDA）批准用于治疗 MDS 的药物并非治愈性药物，其对生存的影响有限；它们包括低甲基化剂（HMA）阿扎胞苷和地西他滨以及 lenalidomide 用于孤立性 del(5q)的 MDS。迄今为止，异基因造血干细胞移植（ASCT）仍然是唯一可能治愈的治疗选择。鉴于目前尚无药物具有令人信服的生存获益证据，我们认为 ASCT 是大多数有症状疾病患者的首选治疗方法，尤其是高危疾病患者。对于不适合移植的患者，我们更倾向于选择参加临床试验，而不是接受常规治疗。对于不适合 ASCT 或临床试验的患者，没有一种正确的治疗方法，选择姑息治疗药物取决于临床问题，如症状性贫血（ESA、danazol、HMA）、血小板减少症（HMA）或中性粒细胞减少症（骨髓生长因子）。相反，没有对照证据支持 MDS 中使用铁螯合剂。展望未来，我们认为现在是将突变信息纳入 MDS 临床衍生预后模型并鼓励开发具有疾病修饰活性的新型药物的时候了。
