The recently updated European LeukemiaNet risk stratification guidelines combine cytogenetic abnormalities and genetic mutations to provide the means to triage patients with acute myeloid leukemia for optimal therapies. Despite the identification of many prognostic factors, relatively few have made their way into clinical practice. In order to assess and improve the performance of the European LeukemiaNet guidelines, we developed novel prognostic models using the biomarkers from the guidelines, age, performance status and select transcript biomarkers. The models were developed separately for mononuclear cells and viable leukemic blasts from previously untreated acute myeloid leukemia patients (discovery cohort, N = 185) who received intensive chemotherapy. Models were validated in an independent set of similarly treated patients (validation cohort, N = 166). Models using European LeukemiaNet guidelines were significantly associated with clinical outcomes and, therefore, utilized as a baseline for comparisons. Models incorporating age and expression of select transcripts with biomarkers from European LeukemiaNet guidelines demonstrated higher area under the curve and C-statistics but did not show a substantial improvement in performance in the validation cohort. Subset analyses demonstrated that models using only the European LeukemiaNet guidelines were a better fit for younger patients (age < 55) than for older patients. Models integrating age and European LeukemiaNet guidelines visually showed more separation between risk groups in older patients. Models excluding results for ASXL1, CEBPA, RUNX1 and TP53, demonstrated that these mutations provide a limited overall contribution to risk stratification across the entire population, given the low frequency of mutations and confounding risk factors. While European LeukemiaNet guidelines remain a critical tool for triaging patients with acute myeloid leukemia, the findings illustrate the need for additional prognostic factors, including age, to improve risk stratification.

中文翻译：

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利用 ELN-2017 指南和其他预后因素的 AML 风险分层模型：SWOG 报告。

最近更新的欧洲 LeukemiaNet 风险分层指南结合了细胞遗传学异常和基因突变，为对急性髓性白血病患者进行分类以获得最佳治疗提供了手段。尽管确定了许多预后因素，但很少有人进入临床实践。为了评估和改进欧洲 LeukemiaNet 指南的性能，我们使用来自指南、年龄、表现状态和选择转录生物标志物的生物标志物开发了新的预后模型。这些模型分别针对先前未治疗的急性髓性白血病患者（发现队列，N = 185）接受强化化疗的单核细胞和存活的白血病原始细胞开发。模型在一组独立的类似治疗的患者（验证队列，N = 166)。使用欧洲 LeukemiaNet 指南的模型与临床结果显着相关，因此被用作比较的基线。将年龄和选择转录物表达与来自欧洲 LeukemiaNet 指南的生物标志物相结合的模型显示出更高的曲线下面积和 C 统计量，但在验证队列中没有显示出显着的性能改善。子集分析表明，仅使用欧洲 LeukemiaNet 指南的模型比老年患者更适合年轻患者（年龄 < 55）。整合年龄和欧洲 LeukemiaNet 指南的模型直观地显示了老年患者风险组之间的更多分离。不包括 ASXL1、CEBPA、RUNX1 和 TP53 结果的模型，证明这些突变对整个人群的风险分层的总体贡献有限，因为突变的频率低和混杂的风险因素。虽然欧洲 LeukemiaNet 指南仍然是对急性髓性白血病患者进行分类的关键工具，但研究结果表明需要额外的预后因素，包括年龄，以改善风险分层。