文章：

一个针对CMML的国际数据集验证了预后评分系统，并显示出对新预后策略的需求

An international data set for CMML validates prognostic scoring systems and demonstrates a need for novel prognostication strategies

原文发布日期：2015-07-31

DOI: 10.1038/bcj.2015.53

类型: Original Article

开放获取: 是

英文摘要：

Since its reclassification as a distinct disease entity, clinical research efforts have attempted to establish baseline characteristics and prognostic scoring systems for chronic myelomonocytic leukemia (CMML). Although existing data for baseline characteristics and CMML prognostication have been robustly developed and externally validated, these results have been limited by the small size of single-institution cohorts. We developed an international CMML data set that included 1832 cases across eight centers to establish the frequency of key clinical characteristics. Of note, we found that the majority of CMML patients were classified as World Health Organization CMML-1 and that a 7.5% bone marrow blast cut-point may discriminate prognosis with higher resolution in comparison with the existing 10%. We additionally interrogated existing CMML prognostic models and found that they are all valid and have comparable performance but are vulnerable to upstaging. Using random forest survival analysis for variable discovery, we demonstrated that the prognostic power of clinical variables alone is limited. Last, we confirmed the independent prognostic relevance of ASXL1 gene mutations and identified the novel adverse prognostic impact imparted by CBL mutations. Our data suggest that combinations of clinical and molecular information may be required to improve the accuracy of current CMML prognostication.

摘要翻译： 

自慢性粒-单核细胞白血病（CMML）被重新界定为独立疾病实体以来，临床研究始终致力于建立其基线特征与预后评分系统。尽管现有数据已稳健构建并完成外部验证，但单中心研究队列规模较小限制了这些结果的普适性。我们建立了国际性CMML数据集，涵盖八个中心的1832个病例，以确定关键临床特征的分布频率。值得注意的是，研究发现多数CMML患者被归类为世界卫生组织CMML-1亚型，且与现行10%标准相比，7.5%骨髓原始细胞截断值可能更精准区分预后分层。通过验证现有CMML预后模型，我们发现所有模型均有效且性能相当，但存在分期升级风险。采用随机森林生存分析进行变量探索，我们证实单纯临床变量的预后预测能力有限。最后研究不仅验证了ASXL1基因突变的独立预后价值，还首次揭示CBL突变的新型不良预后影响。本研究提示，结合临床与分子生物学信息或将提升现有CMML预后预测体系的精确度。

原文链接：

An international data set for CMML validates prognostic scoring systems and demonstrates a need for novel prognostication strategies