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.
Ann Hematol. 2023 Dec;102(12):3575-3585. doi: 10.1007/s00277-023-05477-y. Epub 2023 Oct 9.
Chimeric antigen receptor (CAR) T-cell-associated coagulopathy can cause bleeding events. To explore risk factors for hemorrhage after CAR T-cell therapy, we retrospectively analyzed routine indicators in 56 patients with non-Hodgkin lymphoma and B-cell acute lymphoblastic leukemia who received anti-CD19 CAR T-cell therapy. Disturbance of coagulation occurred mainly within one month post infusion, especially on day 7 and 14. The cumulative incidence of bleeding events within one month was 32.8%, with the median onset of 7 (range, 0-28) days. All bleeding events were grade 1-3. Patients who experienced bleeding events within one month had longer prothrombin time, higher IL-6, higher IL-10, and lower platelets before lymphodepletion. There were also correlations among coagulation-, inflammatory-, and tumor burden-related markers. Multi-variate analysis showed IL-10 (> 7.98 pg/mL; adjusted odds ratio [OR], 13.84; 95% confidence interval [CI], 2.03-94.36; P = 0.007) and the endothelial activation and stress index (EASIX, defined as dehydrogenase [U/L] × creatinine [mg/dL] / platelets [×10 cells/L]; >7.65; adjusted OR, 7.06; 95% CI, 1.03-48.23; P = 0.046) were significant risk factors for bleeding events. IL-10 plus the EASIX defined three risk groups for bleeding events with cumulative incidence of 100% (hazard ratio [HR], 14.47; 95% CI, 2.78-75.29; P < 0.0001), 38.5% (HR, 3.68; 95% CI, 0.82-16.67; P = 0.089), and 11.8% (reference), respectively. Future studies are needed to verify the risk assessment models for bleeding events after CAR T-cell treatment in larger cohorts.
嵌合抗原受体 (CAR) T 细胞相关凝血障碍可导致出血事件。为了探讨 CAR T 细胞治疗后出血的危险因素，我们回顾性分析了 56 例接受抗 CD19 CAR T 细胞治疗的非霍奇金淋巴瘤和 B 细胞急性淋巴细胞白血病患者的常规指标。凝血紊乱主要发生在输注后一个月内，尤其是在第 7 天和第 14 天。一个月内出血事件的累积发生率为 32.8%，中位发病时间为 7（0-28）天。所有出血事件均为 1-3 级。一个月内发生出血事件的患者在淋巴细胞耗竭前的凝血时间较长，IL-6、IL-10 较高，血小板较低。凝血、炎症和肿瘤负荷相关标志物之间也存在相关性。多变量分析显示，IL-10（>7.98pg/mL；调整后的优势比[OR]，13.84；95%置信区间[CI]，2.03-94.36；P=0.007）和内皮激活和应激指数（EASIX，定义为脱氢酶[U/L]×肌酐[mg/dL] /血小板[×10 细胞/L]；>7.65；调整后的 OR，7.06；95%CI，1.03-48.23；P=0.046）是出血事件的显著危险因素。IL-10 加 EASIX 定义了出血事件的三个风险组，累积发生率为 100%（危险比[HR]，14.47；95%CI，2.78-75.29；P<0.0001）、38.5%（HR，3.68；95%CI，0.82-16.67；P=0.089）和 11.8%（参考）。需要进一步的研究来验证更大队列中 CAR T 细胞治疗后出血风险评估模型。
