肿瘤细胞治疗研究
英文原题:Prognostic factor analysis of CD19 CAR-T therapy followed by hematopoietic stem cell transplantation in relapsed/refractory B-ALL.
Prognostic factor analysis of CD19 CAR-T therapy followed by hematopoietic stem cell transplantation in relapsed/refractory B-ALL.
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评估接受 CD19 CAR-T 细胞 治疗后序贯异基因造血干细胞移植 (allo-HSCT) 的复发/难治性 B 细胞急性淋巴细胞白血病 (R/R B-ALL) 患者的长期预后,并识别影响总生存期 (OS) 和急性移植物抗宿主病 (aGVHD) 严重程度的危险因素。对 63 例在接受 CD19 CAR-T 治疗后序贯 allo-HSCT 的 R/R B-ALL 患者进行了回顾性分析。采用 Cox 回归分析识别影响 OS 的因素。根据 aGVHD 严重程度(低级别 vs. 高级别)对患者进行分层。采用 Logistic 回归识别重度 aGVHD 的预测因素,并基于这些预测因素构建列线图。
使用受试者工作特征 (ROC) 曲线、校准图和决策曲线分析 (DCA) 对模型进行内部验证。2 年 OS 率和无进展生存期 (PFS) 率分别为 67.7% 和 55.6%。从 CAR-T 治疗到移植的时间间隔以及高级别 aGVHD 被确定为 OS 的独立危险因素,而低级别 aGVHD 发挥保护作用。从 CAR-T 治疗到移植的较长时间间隔和移植前微小残留病 (MRD) 阳性状态是重度 aGVHD 的独立预测因素。用于预测 aGVHD 严重程度的列线图在内部验证中显示出良好的区分度(曲线下面积 [AUC] = 0.827)、满意的校准度和临床实用性。
我们确定了关键预后因素,并开发了一个经过验证的列线图,能够在此情况下对重度 aGVHD 进行早期、个体化预测。该模型有助于早期风险分层和靶向干预,以改善预后。
To evaluate the long-term prognosis of patients with relapsed/refractory B-cell acute lymphoblastic leukemia (R/R B-ALL) who received sequential allogeneic hematopoietic stem cell transplantation (allo-HSCT) following CD19 Chimeric Antigen Receptor T-cell (CAR-T) therapy, and to identify the risk factors influencing overall survival (OS) and the severity of acute graft-versus-host disease (aGVHD). A retrospective analysis was conducted on 63 patients with R/R B-ALL who received sequential allo-HSCT after CD19 CAR-T therapy. Cox regression analysis was used to identify factors influencing OS. Patients were stratified according to the severity of aGVHD (low-grade vs. high-grade). Logistic regression was employed to identify predictors of severe aGVHD, and a nomogram was constructed based on these predictors.
The model was internally validated using receiver operating characteristic (ROC) curves, calibration plots, and decision curve analysis (DCA). The two-year OS and progression-free survival (PFS) rates were 67. 7% and 55. 6%, respectively. The time interval from CAR-T therapy to transplantation, along with high-grade aGVHD, were identified as independent risk factors for OS, whereas low-grade aGVHD exerted a protective effect.
A longer time interval from CAR-T therapy to transplantation and pre-transplant minimalresidual disease (MRD)-positive status were independent predictors of severe aGVHD. The nomogram developed for predicting the severity of aGVHD demonstrated good discrimination (areaunder the curve [AUC] = 0. 827), satisfactory calibration, and clinical utility upon internal validation.
We identified key prognostic factors and developed a validated nomogram that enables early, individualized prediction of severe aGVHD in this setting. This model can assist in early risk stratification and targeted intervention to improve outcomes.
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