Arai Yasuyuki
Department of Clinical Laboratory Medicine, Center for Research and Application of Cellular Therapy, Department of Hematology and Oncology, Kyoto University Hospital.
Rinsho Ketsueki. 2022;63(9):1205-1211. doi: 10.11406/rinketsu.63.1205.
Chimeric antigen receptor (CAR) T-cell therapy has become the standard of care for some B-cell malignancies due to its high antitumor efficacy. However, adverse events specific to CAR T-cell therapy, such as cytokine release syndrome (CRS), are frequently observed. Typical clinical manifestations of CRS include hyperthermia, hypotension, hypoxemia, and increased vascular permeability. Coagulopathy may also be observed along with to the typical symptoms of CRS. Previous studies, including ours, have revealed that the increase in interleukin-6 levels associated with CRS promotes production of plasminogen activator inhibitor-1 from the vascular endothelium, resulting in suppressed fibrinolysis and hypercoagulability and an exhaustible decrease in fibrinogen. Continuous monitoring of coagulation parameters is necessary during CAR T-cell therapy, and adequate provision of fresh-frozen plasma or cryoprecipitate is recommended if the patient is evaluated to be at high risk for severe CRS.
嵌合抗原受体（CAR）T细胞疗法因其高抗肿瘤疗效已成为某些B细胞恶性肿瘤的标准治疗方法。然而，CAR T细胞疗法特有的不良事件，如细胞因子释放综合征（CRS），却经常出现。CRS的典型临床表现包括高热、低血压、低氧血症和血管通透性增加。凝血障碍也可能与CRS的典型症状同时出现。包括我们的研究在内，先前的研究表明，与CRS相关的白细胞介素-6水平升高会促进血管内皮细胞产生纤溶酶原激活物抑制剂-1，导致纤维蛋白溶解受抑制和高凝状态，以及纤维蛋白原的消耗性降低。在CAR T细胞治疗期间，有必要持续监测凝血参数，如果评估患者发生严重CRS的风险较高，建议充分提供新鲜冰冻血浆或冷沉淀。
