■最近更新的欧洲白血病网络风险分层指南结合了细胞遗传学异常和基因突变,为急性髓细胞性白血病患者的最佳治疗提供了分诊方法。尽管确定了许多预后因素,进入临床实践的相对较少。
■为了评估和改进欧洲白血病网指南的性能,我们使用指南中的生物标志物开发了新的预后模型,年龄,性能状态和选择转录本生物标志物。这些模型是针对先前未经治疗的急性髓细胞性白血病患者的单核细胞和有活力的白血病母细胞分别开发的(发现队列,N=185),接受强化化疗。模型在一组独立的类似治疗的患者中进行了验证(验证队列,N=166)。
■使用欧洲白血病网指南的模型与临床结果显着相关,因此,用作比较的基线。纳入年龄和具有来自欧洲白血病网指南的生物标志物的选择转录物的表达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性能的实质性改善。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岁)。整合年龄和欧洲白血病网指南的模型在视觉上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表明,这些突变对整个人群的风险分层提供了有限的总体贡献。鉴于突变频率低和混杂的危险因素。
虽然欧洲白血病网指南仍然是对急性髓细胞性白血病患者进行分类的重要工具,研究结果表明需要额外的预后因素,包括年龄,改善风险分层。
UNASSIGNED: 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.
UNASSIGNED: 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).
UNASSIGNED: 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.
UNASSIGNED: 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.