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:Severe Motor Weakness Due to Disturbance in Peripheral Nerves Following Tisagenlecleucel Treatment.
Severe Motor Weakness Due to Disturbance in Peripheral Nerves Following Tisagenlecleucel Treatment.
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本研究报告一例在 tisa-cel 治疗后因周围神经障碍出现严重运动无力的患者。
神经毒性是嵌合抗原受体(CAR)T细胞治疗的一种危险并发症,其病理生理机制尚未完全阐明。CAR-T 细胞治疗后出现与中枢神经系统(CNS)毒性无关的运动无力极少见。病例报告:一名42岁难治性弥漫性大B细胞淋巴瘤女性患者接受替沙仑赛(tisa-cel)治疗,第3天发生细胞因子释放综合征(CRS)。经托珠单抗和甲泼尼龙治疗后,CRS迅速缓解。第7天患者出现下肢运动无力,随后逐渐无法行走,但未出现其他提示CNS受累的症状。地塞米松和托珠单抗治疗无效;经大剂量化疗后接受自体干细胞移植,神经病变才改善。下肢神经传导检查显示,随着运动无力加重,复合肌肉动作电位振幅下降;症状改善后,振幅恢复。结合临床症状和神经传导检查,判断运动无力由周围神经功能障碍所致。
本研究报告1例替沙仑赛治疗后因周围神经功能障碍而出现严重运动无力的患者。CAR-T 细胞治疗中也应关注非CNS来源的神经毒性。
Neurotoxicity is one of the dangerous complications of chimeric antigen receptor (CAR) T-cell therapy, while its pathophysiology remains to be fully understood. Motor weakness not associated with central nervous system (CNS) toxicity has rarely been reported after CAR T-cell therapy. CASE REPORT: A 42-year-old female with a refractory diffuse large B-cell lymphoma received tisagenlecleucel (tisa-cel) and developed cytokine release syndrome (CRS) on day 3. She was treated with tocilizumab and methylprednisolone, which resolved CRS promptly. On day 7, motor weakness in lower extremities appeared, and she gradually became unable to walk without showing any other symptoms attributed to CNS disturbances. Whereas dexamethasone and tocilizumab were ineffective, neuropathy improved after high dose chemotherapy followed by autologous stem cell transplantation. Nerve conduction study (NCS) in lower extremities showed a decline in compound muscle action potential amplitude along with worsening of motor weakness, which was restored after improvement of symptoms. Based on symptoms and NCS, her motor weakness was thought to be due to disturbance in peripheral nerves.
This study reports a patient who developed severe motor weakness due to disturbance in peripheral nerves after tisa-cel therapy. Neurotoxicity of non-CNS origin should also be noted in CAR T-cell therapy.
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