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AML risk stratification models utilizing ELN-2017 guidelines and additional prognostic factors: a SWOG report

机译：AML风险分层模型利用ELN-2017指南和额外的预后因素：赠送报告

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Background: 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. Methods: 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). Results: 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. Conclusions: 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.
机译：背景：最近更新的欧洲白血病风险分层指南结合了细胞遗传学异常和基因突变，为急性髓细胞白血病进行急性骨髓性白血病的方法。尽管鉴定了许多预后因素，但相对较少的是进入临床实践。方法：为了评估和改进欧洲白血病指南的表现，我们使用生物标志物从指南，年龄，性能状况和选择转录生物标志物中开发了新的预后模型。该模型是单独开发的，用于单核细胞和来自先前未经处理的急性髓性白血病患者（发现队列，N = 185）的活性白血病毒药接受了深入化疗。模型在独立的类似治疗患者（验证队列，N = 166）中验证。结果：使用欧洲白血病指南的型号与临床结果显着相关，因此利用作为比较的基线。包含来自欧洲Leukemianet指南的生物标志物的年龄和选择转录物的模型在曲线和C统计下显示出更高的区域，但在验证队列中没有表现出显着提高。子集分析证明，仅使用欧洲白血病指南的模型对于年轻患者（年龄<55）而言，使用欧洲的白血病指南比老年患者更好。整合年龄和欧洲白血病指南的模型在视觉上表现出更多的患者风险群之间的分离。除了突变频率低的突变和混淆风险因素的低频率和混淆风险因素，鉴于突变频率和混淆危险因素的低频率，这些突变排除了ASXL1，CEBPA，RunX1和TP53的结果，表明这些突变在整个人口中对风险分层提供了有限的总体贡献。结论：虽然欧洲白血病指南仍然是Trizing患有急性髓性白血病患者的关键工具，但研究结果表明需要额外的预后因素，包括年龄，提高风险分层。

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