Ke Sha, Zhang Tai-Yuan, Wu Zhuo-Lin, Xie Wei, Liu Lin, Du Meng-Yi
Institute of Hematology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China.
Hubei Clinical Medical Center of Cell Therapy for Neoplastic Disease, Wuhan, 430022, China.
Curr Med Sci. 2025 Sep 10. doi: 10.1007/s11596-025-00109-0.
To develop a novel prognostic scoring system for severe cytokine release syndrome (CRS) in patients with B-cell acute lymphoblastic leukemia (B-ALL) treated with anti-CD19 chimeric antigen receptor (CAR)-T-cell therapy, aiming to optimize risk mitigation strategies and improve clinical management.
This single-center retrospective cohort study included 125 B-ALL patients who received anti-CD19 CAR-T-cell therapy from January 2017 to October 2023. These cases were selected from a cohort of over 500 treated patients on the basis of the availability of comprehensive baseline data, documented CRS grading, and at least 3 months of follow-up. Data on patient demographics, treatment history, laboratory parameters, CAR-T-cell characteristics, safety, and efficacy endpoints were collected. CRS severity was graded according to the 2019 ASTCT consensus criteria. Univariate and multivariate logistic regression analyses were conducted to identify factors associated with CRS severity, and a prognostic model was constructed.
The overall incidence of CRS was 67.2%, with 13.6% having grade ≥ 3 (severe) CRS. Higher baseline and post-lymphodepletion minimal residual disease (MRD) levels and neutropenia on day 7 post-infusion were significantly associated with severe CRS. Inflammatory markers (CRP, ferritin, and IL-6) and coagulation dysfunction (APTT) on day 7 post-infusion were also predictive of CRS severity. The prognostic model incorporating these factors demonstrated robust discriminatory ability, with an area under the ROC curve of 0.875.
This study developed a novel prognostic scoring system for severe CRS in Chinese B-ALL patients receiving anti-CD19 CAR-T-cell therapy. The model integrates clinical and laboratory parameters to facilitate early identification and management of severe CRS. Further validation in larger, prospective cohorts is warranted.
为接受抗CD19嵌合抗原受体（CAR）-T细胞治疗的B细胞急性淋巴细胞白血病（B-ALL）患者开发一种新型的严重细胞因子释放综合征（CRS）预后评分系统，旨在优化风险缓解策略并改善临床管理。
这项单中心回顾性队列研究纳入了2017年1月至2023年10月期间接受抗CD19 CAR-T细胞治疗的125例B-ALL患者。这些病例是从500多名接受治疗的患者队列中根据全面基线数据的可用性、记录的CRS分级以及至少3个月的随访情况挑选出来的。收集了患者人口统计学、治疗史、实验室参数、CAR-T细胞特征、安全性和疗效终点的数据。根据2019年美国血液和骨髓移植学会（ASTCT）共识标准对CRS严重程度进行分级。进行单因素和多因素逻辑回归分析以确定与CRS严重程度相关的因素，并构建了一个预后模型。
CRS的总体发生率为67.2%，其中13.6%的患者CRS分级≥3级（严重）。较高的基线和淋巴细胞清除后最小残留病（MRD）水平以及输注后第7天的中性粒细胞减少与严重CRS显著相关。输注后第7天的炎症标志物（CRP、铁蛋白和IL-6）和凝血功能障碍（活化部分凝血活酶时间[APTT]）也可预测CRS严重程度。纳入这些因素的预后模型显示出强大的区分能力，ROC曲线下面积为0.875。
本研究为接受抗CD19 CAR-T细胞治疗的中国B-ALL患者开发了一种新型的严重CRS预后评分系统。该模型整合了临床和实验室参数，便于早期识别和管理严重CRS。有必要在更大的前瞻性队列中进行进一步验证。
