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:Diabetes insipidus and Guillain-Barré-like syndrome following CAR-T cell therapy: a case report.
Diabetes insipidus and Guillain-Barré-like syndrome following CAR-T cell therapy: a case report.
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本病例报告强调了接受 CAR-T 细胞治疗的患者中出现罕见但严重的神经系统不良事件(如急性 GBS 或 cDI)的风险。
免疫效应细胞相关神经毒性综合征(ICANS)是靶向CD19的嵌合抗原受体(CAR)T细胞治疗常见的不良事件。然而,其他神经系统不良事件尚未得到系统描述和研究。此外,CAR-T 细胞疗法用于中枢神经系统(CNS)淋巴瘤患者的安全性数据仍有限。正文:本文报告一例复发性高级别淋巴瘤伴CNS受累患者接受tisagenlecleucel治疗后发生格林-巴利样综合征(GBS)和中枢性尿崩症(cDI)。两种并发症均对ICANS标准治疗无反应。呼吸肌无力需要机械通气和气管切开;cDI则通过数周去氨加压素替代治疗控制。肌肉-神经活检和神经传导检查证实神经损伤呈轴索型。肌肉-神经组织切片中富含T细胞的浸润以及检测到CAR转基因,提示CAR-T 细胞介导的炎症可能直接或间接参与其中。依照现行GBS治疗指南,患者接受静脉注射免疫球蛋白,数月内逐渐恢复,但未完全康复。
本病例提示接受CAR-T 细胞治疗的患者可能发生急性GBS或cDI等罕见但严重的神经系统不良事件。它也进一步强调,适当的患者监测以及系统报告罕见并发症十分重要,这有助于最终改进治疗。
Immune effector cell-associated neurotoxicity syndrome (ICANS) is a common adverse event of CD19-directed chimeric antigen receptor (CAR) T cell therapy. Other neurological adverse events, however, have not methodically been described and studied. Furthermore, safety data on CAR-T cell therapy in patients with central nervous system (CNS) lymphoma remain limited. MAIN BODY: We here report occurrence of a Guillain-Barr -like syndrome (GBS) and central diabetes insipidus (cDI) following tisagenlecleucel therapy for relapsed high-grade lymphoma with CNS involvement. Both complications were refractory to standard treatment of ICANS. Weakness of respiratory muscles required mechanical ventilation and tracheostomy while cDI was treated with desmopressin substitution for several weeks. Muscle-nerve biopsy and nerve conduction studies confirmed an axonal pattern of nerve damage. T cell-rich infiltrates and detection of the CAR transgene in muscle-nerve sections imply a direct or indirect role of CAR-T cell-mediated inflammation. In line with current treatment guidelines for GBS, intravenous immunoglobulin was administered and gradual but incomplete recovery was observed over the course of several months.
This case report highlights the risk of rare but severe neurological adverse events, such as acute GBS or cDI, in patients treated with CAR-T cells. It further underlines the importance of appropriate patient surveillance and systematic reporting of rare complications to eventually improve treatment.
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