1 Médecine Intensive et Réanimation, Assistance Publique des Hôpitaux de Paris, St-Louis Teaching Hospital and Paris 7 University, Paris, France.
2 Groupe de Recherche Respiratoire en Reanimation Onco-Hématologique, Paris, France.
Am J Respir Crit Care Med. 2019 Jul 1;200(1):20-23. doi: 10.1164/rccm.201810-1945ED.
CAR (chimeric antigen receptor) T cells (CARTs) are genetically engineered T cells that express CARs, with impressive clinical activity in relapsed and refractory hematologic malignancies, primarily acute lymphoblastic leukemia and diffuse large B-cell lymphoma. The most frequent life-threatening adverse events after CART infusion are cytokine release syndrome and CAR-related encephalopathy syndrome, which can occur within hours or days after administration. IL-6 released by macrophages and monocytes plays a major role in the pathogenesis of cytokine release syndrome and CAR-related encephalopathy syndrome, and IL-6 blockade and steroids contribute to fast resolution of symptoms. Critical care management plays an important role in patients receiving CARTs, as up to half of patients might need an admission to the ICU and lifesaving interventions. As new treatment indications and CART constructs enter the clinic, the number of patients requiring ICU admission will rapidly increase, with profound consequences for the use of ICU resources, training requirements, clinical expertise, multidisciplinary collaboration, and hospital organization. Research is also needed to validate at large scale biomarkers that allow doctors to risk-stratify patients for both their risk to develop severe toxicity and their likelihood to respond to therapy.
嵌合抗原受体 (CAR) T 细胞 (CARTs) 是经过基因工程改造的 T 细胞，在复发和难治性血液系统恶性肿瘤中具有显著的临床活性，主要是急性淋巴细胞白血病和弥漫性大 B 细胞淋巴瘤。CART 输注后最常见的危及生命的不良事件是细胞因子释放综合征和 CAR 相关脑病综合征，这些综合征可在给药后数小时或数天内发生。巨噬细胞和单核细胞释放的白细胞介素 6 (IL-6) 在细胞因子释放综合征和 CAR 相关脑病综合征的发病机制中起主要作用，IL-6 阻断和类固醇有助于快速缓解症状。在接受 CART 治疗的患者中，重症监护管理起着重要作用，因为多达一半的患者可能需要入住 ICU 并进行救生干预。随着新的治疗适应证和 CART 结构进入临床，需要入住 ICU 的患者数量将迅速增加，这对 ICU 资源的使用、培训要求、临床专业知识、多学科协作和医院组织都产生了深远的影响。还需要研究来验证大规模的生物标志物，这些标志物可以让医生对患者的严重毒性风险和对治疗的反应可能性进行风险分层。
