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复发/难治性 B-ALL 中 CD19 CAR-T 治疗序贯造血干细胞移植的预后因素分析

英文原题:Prognostic factor analysis of CD19 CAR-T therapy followed by hematopoietic stem cell transplantation in relapsed/refractory B-ALL.

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Prognostic factor analysis of CD19 CAR-T therapy followed by hematopoietic stem cell transplantation in relapsed/refractory B-ALL.

PubMed 2026/07/30(内容时间) Clin Exp Med Q2 · IF 4.5(JCR 2025)

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中文摘要

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。

展开英文摘要原文

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.

论文信息

作者
Wang X、Liu L、Zhai Y、Xu J、Liu J、Lyu H、Zhao M
第一作者单位
First Central Hospital of Tianjin Medical University, Tianjin Medical University, Tianjin, China.China
通讯作者单位
Department of Hematology, Tianjin Thrombosis and Hemostasis Institute, Tianjin First Central Hospital, No.2 Baoshan West Road, Xiqing District, Tianjin, 300192, China. mingfengzhao@sina.com.China
期刊
Clinical and experimental medicine2026 Jul 30
原文标识
PubMed 42606754 · DOI 10.1007/s10238-026-02273-6