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儿童急性髓系白血病风险分层预后评分模型的开发与验证

Development and validation of a prognostic scoring model to risk stratify childhood acute myeloid leukaemia.

作者信息

Li Jun, Liu Lipeng, Zhang Ranran, Wan Yang, Gong Xiaowen, Zhang Li, Yang Wenyu, Chen Xiaojuan, Zou Yao, Chen Yumei, Guo Ye, Ruan Min, Zhu Xiaofan

机构信息

State Key Laboratory of Experimental Hematology, National Clinical Research Center for Blood Diseases, Haihe Laboratory of Cell Ecosystem, Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Tianjin, China.

出版信息

Br J Haematol. 2022 Sep;198(6):1041-1050. doi: 10.1111/bjh.18354. Epub 2022 Jul 25.

Abstract

To create a personal prognostic model and modify the risk stratification of paediatric acute myeloid leukaemia, we downloaded the clinical data of 597 patients from the Therapeutically Applicable Research to Generate Effective Treatments (TARGET) database as a training set and included 189 patients from our centre as a validation set. In the training set, age at diagnosis, -7/del(7q) or -5/del(5q), core binding factor fusion genes, FMS-like tyrosine kinase 3-internal tandem duplication (FLT3-ITD)/nucleophosmin 1 (NPM1) status, Wilms tumour 1 (WT1) mutation, biallelic CCAAT enhancer binding protein alpha (CEBPA) mutation were strongly correlated with overall survival and included to construct the model. The prognostic model demonstrated excellent discriminative ability with the Harrell's concordance index of 0.68, 3- and 5-year area under the receiver operating characteristic curve of 0.71 and 0.72 respectively. The model was validated in the validation set and outperformed existing prognostic systems. Additionally, patients were stratified into three risk groups (low, intermediate and high risk) with significantly distinct prognosis, and the model successfully identified candidates for haematopoietic stem cell transplantation. The newly developed prognostic model showed robust ability and utility in survival prediction and risk stratification, which could be helpful in modifying treatment selection in clinical routine.

摘要

为创建个人预后模型并修改小儿急性髓系白血病的风险分层,我们从治疗性应用研究以生成有效治疗方法(TARGET)数据库下载了597例患者的临床数据作为训练集,并纳入了来自我们中心的189例患者作为验证集。在训练集中,诊断时的年龄、-7/del(7q)或-5/del(5q)、核心结合因子融合基因、FMS样酪氨酸激酶3内部串联重复(FLT3-ITD)/核仁磷酸蛋白1(NPM1)状态、威尔姆斯瘤1(WT1)突变、双等位基因CCAAT增强子结合蛋白α(CEBPA)突变与总生存期密切相关,并纳入构建模型。该预后模型显示出优异的判别能力,Harrell一致性指数为0.68,受试者操作特征曲线下3年和5年面积分别为0.71和0.72。该模型在验证集中得到验证,且优于现有的预后系统。此外,患者被分为三个风险组(低、中、高风险),预后显著不同,该模型成功识别了造血干细胞移植的候选者。新开发的预后模型在生存预测和风险分层方面显示出强大的能力和实用性,有助于在临床常规中修改治疗选择。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e597/9543487/cae0c31686a6/BJH-198-1041-g003.jpg

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