肿瘤细胞治疗研究
英文原题:Prospective observational study of magnetic resonance imaging in anti-CD19 CAR T-cell-associated neurotoxicity.
Prospective observational study of magnetic resonance imaging in anti-CD19 CAR T-cell-associated neurotoxicity.
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系列脑部 MRI 能够识别出两种与 ICANS 相关的特定影像学特征,二者具有不同的时间与影像学特点。
**背景:**免疫效应细胞相关神经毒性综合征(ICANS)是抗CD19 CAR-T 细胞治疗常见且可能严重的并发症。然而,其神经放射学特征尚未得到充分界定,因为现有证据大多来自回顾性队列、影像方案不一致的研究,或仅涉及儿童患者的研究。**方法:**本单中心前瞻性研究纳入接受抗CD19 CAR-T 细胞治疗的成人B细胞淋巴增殖性疾病患者。所有患者均接受标准化神经学和神经放射学评估;脑MRI安排在筛查时(CAR-T 输注前15–20天)、输注后60天和12个月进行,发生ICANS时另行急诊检查。由专家神经放射科医师组成的小组审阅MRI记录。**结果:**154例接受治疗的患者中,112例纳入研究。34例(30.4%)发生ICANS,其中27例接受急诊MRI,11例(40.7%)可见异常。
研究识别出两种不同的影像模式。中枢型模式表现为丘脑、海马、脑干以及可能伴随膝状体或胼胝体的对称性受累,与重度ICANS和临床急性恶化相关;其中两例出现半卵圆中心弥漫性水肿和颅内压增高。随访影像显示多数此类改变消退。类卒中模式表现为局灶性皮质—皮质下白质病灶,常有弥散加权成像受限;病灶既见于ICANS患者,也见于无症状患者,通常出现在亚急性阶段。随访时,这些病灶持续表现为无强化的FLAIR异常。**结论:**连续脑MRI检查识别出两种具有不同时间进程和影像特征的ICANS相关模式。尽管MRI对ICANS的总体敏感度仍较低,识别特定模式有助于提高诊断特异性、支持临床鉴别诊断,并增进对潜在病理生理机制的认识。
Immune effector cell-associated neurotoxicity syndrome (ICANS) is a frequent and potentially severe complication of anti-CD19 CAR T-cell therapy. Nevertheless, its neuroradiological characterization remains insufficiently defined, as most available evidence stems from retrospective cohorts, heterogeneous imaging protocols, or studies limited to pediatric populations.
We conducted a prospective, monocentric study including adult patients with B-cell lymphoproliferative disorders undergoing anti-CD19 CAR T-cell therapy. All patients underwent a standardized neurological and neuroradiological protocol, with brain MRI performed at screening (15-20 days before CAR T-cell infusion), 60 days, and 12 months after infusion, as well as urgently in the event of ICANS. Brain MRI records were reviewed by a panel of expert neuroradiologists.
Of 154 treated patients, 112 were included. ICANS occurred in 34 patients (30.4%); 27 underwent urgent MRI, which showed abnormalities in 11 cases (40.7%). Two distinct radiological patterns emerged. The central variant pattern-characterized by symmetric involvement of thalami, hippocampi, brainstem, and variably the geniculate bodies or corpus callosum-was associated with severe ICANS and acute clinical deterioration, including two cases with diffuse centrum semiovale edema and intracranial hypertension. This pattern resolved in most cases on follow-up imaging. The stroke-like pattern consisted of focal cortico-subcortical white matter lesions, often DWI-restricted, appearing in both ICANS and asymptomatic patients, typically in subacute phases. These lesions persisted as non-enhancing FLAIR abnormalities at follow-up.
Serial brain MRI enabled identification of two specific ICANS-related imaging signatures with distinct temporal and radiological characteristics. While overall MRI sensitivity for ICANS remains low, pattern recognition improves diagnostic specificity, supports clinicians in the differential diagnosis, and provides insights into underling pathophysiology.
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