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.
CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
英文原题:Functional connectivity MRI provides an imaging correlate for chimeric antigen receptor T-cell-associated neurotoxicity.
Functional connectivity MRI provides an imaging correlate for chimeric antigen receptor T-cell-associated neurotoxicity.
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基于 rsfMRI 的 DCI 可能适合直接量化接受 CAR-T 输注的个体患者 ICANS 的严重程度。
采用嵌合抗原受体修饰T细胞(CAR-T)治疗血液系统恶性肿瘤疗效显著,但常受到免疫效应细胞相关神经毒性综合征(ICANS)限制。ICANS期间常规MRI往往无明显异常,因此我们旨在考察静息态功能MRI(rsfMRI)是否适用于呈现并量化个体患者发生ICANS时的脑网络改变。
在系统性淋巴瘤患者及1例黑色素瘤患者中,纵向评估ICANS期间以及临床缓解前后基于rsfMRI计算的失连接指数(DCI)。
共纳入7例淋巴瘤患者和1例黑色素瘤患者(年龄19–77岁,女性2例)。ICANS期间DCI显著升高,康复后恢复正常(P=0.0039)。ICANS分级越高,DCI评分越高,二者显著相关(r=0.7807;P=0.0222)。DCI升高最明显的区域包括语言优势半球额下回和额盖(即Broca区),以及颞上回后部和颞顶交界区(即Wernicke区),与非流利性失语和失用等主要临床症状相符。
基于rsfMRI的DCI可能适用于直接量化接受CAR-T 输注患者ICANS的严重程度。除ICANS外,DCI似乎也是一种有前景的诊断工具,可用于量化不同病因脑病期间的功能性脑网络改变。
Treatment of hematological malignancies with chimeric antigen receptor modified T cells (CART) is highly efficient, but often limited by an immune effector cell-associated neurotoxicity syndrome (ICANS). As conventional MRI is often unremarkable during ICANS, we aimed to examine whether resting-state functional MRI (rsfMRI) is suitable to depict and quantify brain network alterations underlying ICANS in the individual patient.
The dysconnectivity index (DCI) based on rsfMRI was longitudinally assessed in systemic lymphoma patients and 1 melanoma patient during ICANS and before or after clinical resolution of ICANS.
Seven lymphoma patients and 1 melanoma patient (19-77 years; 2 female) were included. DCI was significantly increased during ICANS with normalization after recovery ( P = .0039). Higher ICANS grades were significantly correlated with increased DCI scores ( r = 0.7807; P = .0222). DCI increase was most prominent in the inferior frontal gyrus and the frontal operculum (ie, Broca's area) and in the posterior parts of the superior temporal gyrus and the temporoparietal junction (ie, Wernicke's area) of the language-dominant hemisphere, thus reflecting the major clinical symptoms of nonfluent dysphasia and dyspraxia.
RsfMRI-based DCI might be suitable to directly quantify the severity of ICANS in individual patients undergoing CAR T-transfusion. Besides ICANS, DCI seems a promising diagnostic tool to quantify functional brain network alterations during encephalopathies of different etiologies, in general.
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