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:Brain MRI changes in children and young adults with B-cell acute lymphoblastic leukemia following chimeric antigen receptor T-cell therapy.
Brain MRI changes in children and young adults with B-cell acute lymphoblastic leukemia following chimeric antigen receptor T-cell therapy.
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B-ALL 儿童和年轻成人在 CAR-T 细胞治疗后可出现脑 MRI 异常,以 WM 信号改变为主。
评估 B 急性淋巴细胞白血病(B-ALL)儿童和青年患者接受嵌合抗原受体(CAR)T 细胞治疗后的脑 MRI 表现,并分析其与临床及神经系统症状的关联。
回顾单一机构 2015 年 4 月至 2023 年 10 月期间接受治疗、年龄不超过 25 岁的 B-ALL 患者 CAR-T 治疗前后脑 MRI。将 MRI 异常分为无变化、既存病变加重或新发病变。记录 CAR 介导的临床毒性,包括细胞因子释放综合征(CRS)和免疫效应细胞相关神经毒性综合征(ICANS)分级。按有无“加重/新发病变”分组,并使用 Fisher 精确检验比较临床及神经系统症状。
共有 16 例患者有治疗前后脑 MRI,纳入分析;中位年龄 16 岁[四分位距 11–21],男性 9 例、女性 7 例。81%(13/16)患者治疗后出现脑部异常,包括白质信号改变(12/16)、软脑膜强化(1/16)和小脑栓塞性梗死(1/16)。治疗后白质病变中,50%(6/12)较治疗前加重,33%(4/12)为新发,17%(2/12)无变化。有无“加重/新发病变”的患者之间,CRS(p = 0.079)或 ICANS 分级(p > 0.99)均无差异。
B-ALL 儿童和青年患者接受 CAR-T 治疗后可出现脑 MRI 异常,主要为白质信号改变。这些脑部异常与较高级别 CRS 或 ICANS 无相关性。要点:问题——B-ALL 患者 CAR-T 治疗后的脑 MRI 表现及其与临床和神经系统症状的关联尚不清楚。发现——81% 患者出现脑 MRI 异常,以白质改变为主,但未发现其与 CAR 介导毒性相关。临床意义——CAR-T 后常见的脑 MRI 异常与 CAR 相关毒性严重程度无关,有助于这些患者的临床管理和监测。
To evaluate brain MRI findings in children and young adults after chimeric antigen receptor (CAR) T-cell therapy for B-cell acute lymphoid leukemia (B-ALL) and associate results with clinical and neurological symptoms.
We reviewed pre- and post-CAR-T cell therapy brain MRIs of B-ALL patients aged 25 years or younger who underwent therapy between April 2015 and October 2023 at a single institution. MRI abnormalities were categorized as no change, exacerbation of preexisting lesion, or newly developed lesion. Clinical CAR-mediated toxicities, including cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS) grades, were recorded. Patients were grouped into those with and without 'exacerbated/new lesion,' and clinical and neurological symptoms were compared using Fisher's exact test.
Sixteen patients with pre- and post-CAR brain MRIs (median age 16 years [interquartile range, 11-21]; 9 males, 7 females) were included in the analysis. Post-CAR brain abnormalities were observed in 81% (13/16) of patients, including white matter (WM) signal changes (12/16), leptomeningeal enhancement (1/16), and cerebellar embolic infarction (1/16). Of the post-CAR WM lesions, 50% (6/12) were exacerbated, 33% (4/12) were newly developed, and 17% (2/12) remained unchanged compared to pre-CAR brain MRI. No difference in CRS (p = 0.079) or ICANS grades (p > 0.99) was observed between patients with and without 'exacerbated/new lesions'.
Children and young adults with B-ALL can develop brain MRI abnormalities after CAR T-cell therapy, predominantly WM signal changes. These brain abnormalities did not show an association with higher CRS or ICANS grade. KEY POINTS: Question Brain MRI findings after chimeric antigen receptor (CAR) T-cell therapy for B-cell acute lymphoid leukemia (B-ALL) and their association with clinical and neurological symptoms are not well understood. Findings Brain MRI abnormalities, mostly white matter changes, were seen in 81% of patients but were not associated with CAR-mediated toxicities. Clinical relevance Brain MRI abnormalities, commonly observed post-CAR T-cell therapy, do not correlate with the severity of CAR-related toxicities, aiding in the clinical management and monitoring of these patients.
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