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:EEG findings in CAR T-cell-associated neurotoxicity: Clinical and radiological correlations.
EEG findings in CAR T-cell-associated neurotoxicity: Clinical and radiological correlations.
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在接受 CAR-T 细胞输注后出现神经毒性的成年患者中,EEG 背景活动紊乱程度与神经毒性严重程度相关。
嵌合抗原受体(CAR)T细胞治疗后常有脑电图(EEG)异常的报告,但其临床意义仍不清楚。我们拟系统描述一家大型单中心队列的EEG特征,并将其与临床和影像学发现进行关联分析。
回顾性识别接受CAR-T 细胞治疗并进行连续EEG监测的患者。收集神经毒性分级、详细神经系统症状以及脑MRI或FDG-PET资料,并评估临床和影像学发现与EEG特征之间的相关性。
81例患者的神经毒性中位分级为3级(四分位距2–3);最常见的EEG表现为弥漫性背景减慢,且与神经毒性严重程度相关(P<0.001)。共42例患者出现节律性或周期性图形,其中16例处于发作-发作间期连续谱(IIC),5例有临床发作,3例仅有脑电图发作。22例患者存在局灶性EEG异常,包括局灶性周期性放电(LPD,n=1)、局灶性节律性δ活动(LRDA,n=6)或局灶性减慢(n=19)。所有LRDA和LPD患者,以及19例局灶性减慢患者中的10例,均出现与相应EEG异常部位一致的局灶性临床症状。此外,在无结构性病灶的情况下,这些局灶性EEG变化常与PET低代谢或MRI低灌注相关。
CAR-T 细胞输注后发生神经毒性的成人患者中,EEG背景紊乱程度与神经毒性严重程度相关。IIC图形和局灶性EEG异常很常见,且常与局灶性临床症状以及PET低代谢/MRI低灌注相关,即使不存在结构性病灶亦如此。这些发现的病因仍有待阐明。
While EEG is frequently reported as abnormal after chimeric antigen receptor (CAR) T-cell therapy, its clinical significance remains unclear. We aim to systematically describe EEG features in a large single-center cohort and correlate them with clinical and radiological findings.
We retrospectively identified patients undergoing CAR T-cell therapy who had continuous EEG. Neurotoxicity grades, detailed neurological symptoms, and brain MRI or FDG-PET were obtained. Correlation between clinical and radiological findings and EEG features was assessed.
In 81 patients with median neurotoxicity grade 3 (IQR 2-3), diffuse EEG background slowing was the most common finding and correlated with neurotoxicity severity (P <.001). A total of 42 patients had rhythmic or periodic patterns, 16 of them within the ictal-interictal-continuum (IIC), 5 with clinical seizures, and 3 with only electrographic seizures. Focal EEG abnormalities, consisting of lateralized periodic discharges (LPD, n = 1), lateralized rhythmic delta activity (LRDA, n = 6), or focal slowing (n = 19), were found in 22 patients. All patients with LRDA, LPD, and 10/19 patients with focal slowing had focal clinical symptoms concordant with these EEG abnormalities. In addition, these focal EEG changes are often correlated with PET hypometabolism or MRI hypoperfusion, in absence of a structural lesion.
In adult patients experiencing neurotoxicity after CAR T-cell infusion, EEG degree of background disorganization correlated with neurotoxicity severity. IIC patterns and focal EEG abnormalities are frequent and often correlate with focal clinical symptoms and with PET-hypometabolism/MRI-hypoperfusion, without structural lesion. The etiology of these findings remains to be elucidated.
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