CAR-T(CAR-T)细胞疗法在非肿瘤性疾病中的应用
Chimeric antigen receptor T (CAR-T) cell therapy in non-oncological diseases.
CAR-T(CAR-T)细胞在血液系统恶性肿瘤中的应用推动了这种免疫治疗形式的显著进展。
CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
英文原题:An International Survey on Grading, Diagnosis, and Management of Immune Effector Cell-Associated Hematotoxicity (ICAHT) Following CAR T-cell Therapy on Behalf of the EBMT and EHA.
An International Survey on Grading, Diagnosis, and Management of Immune Effector Cell-Associated Hematotoxicity (ICAHT) Following CAR T-cell Therapy on Behalf of the EBMT and EHA.
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血液学毒性是嵌合抗原受体(CAR)T细胞治疗后最常见的3级毒性。然而,其潜在的病理生理学尚未完全阐明,其分级和管理仍不明确。为即将发布的欧洲血液学协会/欧洲血液和骨髓移植学会(EHA/EBMT)关于“免疫效应细胞相关血液毒性”(ICAHT)管理指南提供参考,我们通过在线调查对经验丰富的临床医生进行了调查,重点关注(1)分级,(2)风险分层和诊断检查,(3)短期管理,以及(4)ICAHT的长期管理。共有来自18个国家的81名受访者参与调查。在血细胞减少的分级方面,就深度、持续时间和距CAR-T 输注的时间而言,存在高度变异性。大多数专家支持CAR-T 治疗前进行骨髓检查,尤其是在高风险特征的情况下。
大多数受访者认为,对于严重血液毒性患者的检查应排除病毒感染(96%)、底物缺乏(80%)或合并sHLH/MAS(血清铁蛋白,92%),并应包括骨髓穿刺(86%)和/或活检(61%)。关于合并免疫毒性的发生是否应影响应用G-CSF的决策,以及何时开始G-CSF支持,临床医生意见不一。在持续性血小板减少症的情况下,大多数调查参与者支持使用血小板生成素激动剂(86%)。相反,自体造血细胞支持是中性粒细胞减少症的首选(63%),尽管其常常不可获得,且关于最佳触发点未达成共识。这些发现凸显了当前关于ICAHT的实践模式存在异质性,并呼吁制定共识指南,以统一分级、建立诊断的标准操作流程并制定管理指南。
Hematological toxicity represents the most common grade 3 toxicity after chimeric antigen receptor (CAR) T-cell therapy.
However, its underlying pathophysiology is incompletely understood and its grading and management remains ill-defined. To inform the forthcoming European Hematology Association/European Society for Blood and Marrow Transplantation (EHA/EBMT) guidelines on the management of "immune effector cell-associated hematotoxicity" (ICAHT), we undertook a survey of experienced clinicians using an online survey focusing on (1) grading, (2) risk-stratification and diagnostic work-up, (3) short-term, and (4) long-term management of ICAHT. There were 81 survey respondents across 18 countries. A high degree of variability was noted for cytopenia grading in regards to depth, duration, and time from CAR-T infusion. The majority of experts favored pre-CAR-T bone marrow studies, especially in case of a high-risk profile.
Most respondents felt that the work-up for patients with severe hematotoxicity should rule-out viral infections (96%), substrate deficiency (80%), or coincident sHLH/MAS (serum ferritin, 92%), and should include bone marrow aspiration (86%) and/or biopsy (61%). Clinicians were divided as to whether the occurrence of coincident immunotoxicity should influence the decision to apply G-CSF, and when to initiate G-CSF support.
In case of prolonged thrombocytopenia, most survey participants favored thrombopoietin agonists (86%). Conversely, autologous hematopoietic cell boosts represented the preferred choice for neutropenia (63%), although they were frequently not available and no consensus was reached regarding the optimal trigger point.
These findings underline the current heterogeneity of practice patterns regarding ICAHT and invite the development of consensus guidelines, which may harmonize grading, establish standard operating procedures for diagnosis, and set management guidelines.
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