Mao Rui, Hu Shaoxuan, Zhang Yuanchuan, Du Feng, Zhang Yu, Liu Yanjun, Zhang Tongtong
The Affiliated Hospital of Southwest Jiaotong University, Chengdu, China.
Department of Hematology, Peking University Cancer Hospital and Institute, Beijing, China.
Front Oncol. 2020 Sep 10;10:1673. doi: 10.3389/fonc.2020.01673. eCollection 2020.
Despite that the survival rate in childhood acute lymphoblastic leukemia (cALL) is excellent, subsets of high-risk patients with cALL still have high relapse rates, and the cure rate is well below that for which we should aim. The present study aims to construct a prognostic nomogram to better inform clinical practitioners and improve risk stratification for clinical trials.
The developed nomogram was based on the therapeutically applicable research to generate effective treatment (TARGET) database. With this database, we obtained 673 cALL patients with complete clinical information. We identified and integrated significant prognostic factors to build the nomogram model by univariate and multivariate Cox analysis. The predictive accuracy and discriminative ability of the nomogram were determined by the concordance index (C-index), calibration curve, and area under the receiver operating characteristic (ROC) curve (AUC) of ROC analysis. Internal validations were assessed by the bootstrapping validation.
In the multivariate analysis of the primary cohort, the independent factors for survival were ETV6 RUNX1 fusion status, karyotype, minimal residual disease (MRD) at day 29, and DNA index, which were all integrated into the nomogram. The calibration curve for the probability of survival showed good agreement between the prediction by the nomogram and the actual observation. The C-index of the nomogram for predicting survival was 0.754 (95% CI, 0.715-0.793), and the AUCs for 3-, 5-, and 7-year survival were 0.775, 0.776, and 0.772, respectively.
We comprehensively evaluated the risk of clinical factors associated with prognosis and carried out risk stratification. The nomogram proposed in this study objectively and accurately predicted the prognosis of children with ALL.
尽管儿童急性淋巴细胞白血病（cALL）的生存率很高，但高危cALL患者亚组的复发率仍然很高，治愈率远低于我们应达到的目标。本研究旨在构建一个预后列线图，以便更好地为临床医生提供信息，并改善临床试验的风险分层。
所开发的列线图基于治疗性适用研究以生成有效治疗（TARGET）数据库。利用该数据库，我们获得了673例具有完整临床信息的cALL患者。我们通过单因素和多因素Cox分析识别并整合显著的预后因素，以构建列线图模型。列线图的预测准确性和判别能力通过一致性指数（C指数）、校准曲线以及ROC分析的受试者操作特征（ROC）曲线下面积（AUC）来确定。通过自举验证评估内部有效性。
在主要队列的多因素分析中，生存的独立因素为ETV6 RUNX1融合状态、核型、第29天的微小残留病（MRD）和DNA指数，这些因素均被纳入列线图。生存概率的校准曲线显示列线图预测与实际观察之间具有良好的一致性。列线图预测生存的C指数为0.754（95%CI，0.715 - 0.793），3年、5年和7年生存的AUC分别为0.775、0.776和0.772。
我们全面评估了与预后相关的临床因素的风险并进行了风险分层。本研究中提出的列线图客观准确地预测了ALL患儿的预后。
