骨髓增生异常综合症（MDS）是异质性髓系肿瘤，需要风险适应性的治疗策略。最近，提出了一种新的临床-分子预后模型，分子国际预后评分系统（IPSS-M），用于改进当前可用工具（修订版国际预后评分系统[IPSS-R]）对临床结果的预测。我们旨在对IPSS-M进行广泛的验证。共回顾分析了GenoMed4All贡献团队的2,876名原发性MDS患者。相对于IPSS-R，IPSS-M在所有临床终点上都改善了预测判别能力（整体生存率的协调性分别为0.81与0.74，白血病无转化生存率的协调性分别为0.89与0.76）。即使在那些未检测到基因突变的患者中，这也成立。与基于IPSS-R的分层相比，IPSS-M的风险组在46％的患者中发生变化（23.6％和22.4％的受试者升级和降级，分别）。在接受造血干细胞移植（HSCT）治疗的患者中，IPSS-M显著改善了与IPSS-R相比疾病复发风险的预测和移植后生存率的概率（整体生存率的协调性分别为0.76与0.60，复发概率的协调性分别为0.89与0.70）。在用低甲基化剂（HMA）治疗的高危患者中，IPSS-M未能分层个体反应概率；反应持续时间和生存概率与IPSS-M风险呈反比例关系。最后，我们测试了当缺失分子信息时IPSS-M的预测准确性，并定义了一组最少15个相关基因，与得分高的表现有关。IPSS-M可以改善MDS预测，并可能导致更有效地选择接受HSCT的候选者。除基因突变外，其他因素可能参与决定HMA的敏感性。定义一组最少的相关基因可以促进得分的临床实施。

Myelodysplastic syndromes (MDS) are heterogeneous myeloid neoplasms in which a risk-adapted treatment strategy is needed. Recently, a new clinical-molecular prognostic model, the Molecular International Prognostic Scoring System (IPSS-M) was proposed to improve the prediction of clinical outcome of the currently available tool (Revised International Prognostic Scoring System [IPSS-R]). We aimed to provide an extensive validation of IPSS-M.A total of 2,876 patients with primary MDS from the GenoMed4All consortium were retrospectively analyzed.IPSS-M improved prognostic discrimination across all clinical end points with respect to IPSS-R (concordance was 0.81 v 0.74 for overall survival and 0.89 v 0.76 for leukemia-free survival, respectively). This was true even in those patients without detectable gene mutations. Compared with the IPSS-R based stratification, the IPSS-M risk group changed in 46% of patients (23.6% and 22.4% of subjects were upstaged and downstaged, respectively).In patients treated with hematopoietic stem cell transplantation (HSCT), IPSS-M significantly improved the prediction of the risk of disease relapse and the probability of post-transplantation survival versus IPSS-R (concordance was 0.76 v 0.60 for overall survival and 0.89 v 0.70 for probability of relapse, respectively). In high-risk patients treated with hypomethylating agents (HMA), IPSS-M failed to stratify individual probability of response; response duration and probability of survival were inversely related to IPSS-M risk.Finally, we tested the accuracy in predicting IPSS-M when molecular information was missed and we defined a minimum set of 15 relevant genes associated with high performance of the score.IPSS-M improves MDS prognostication and might result in a more effective selection of candidates to HSCT. Additional factors other than gene mutations can be involved in determining HMA sensitivity. The definition of a minimum set of relevant genes may facilitate the clinical implementation of the score.