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:Case Report: Fatal cytomegalovirus pneumonia after CAR-T cell therapy in the long-term follow-up.
Case Report: Fatal cytomegalovirus pneumonia after CAR-T cell therapy in the long-term follow-up.
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CMV 感染/再激活可在接受抗 CD19/22 CAR-T 细胞治疗很久之后发生,并可诱发致死性肺炎,这提醒我们注意 CAR-T 细胞输注后与免疫抑制相关的远期副作用。
引言:CAR-T 细胞疗法快速发展,具有独特的不良反应谱,尤其是迟发毒性,其特点可能尚未被完全认识和理解。巨细胞病毒(CMV)广泛存在,并可终身潜伏;在免疫功能低下宿主中,CMV可导致危及生命的并发症,但CAR-T 治疗后CMV疾病的相关知识有限。本文报告一例复发性B-ALL患者接受抗CD19/CD22 CAR-T 治疗3个月后可能发生CMV肺炎的病例,以增进对CAR-T 输注患者病毒感染或再激活相关严重副作用的认识。病例介绍:一名21岁复发性B-ALL男性患者接受抗CD19/CD22 CAR-T 治疗后,于2周达到完全缓解。3个月后,患者再次住院,入院前发热、咳嗽10天,并有心悸、胸闷3天,临床诊断为可能的CMV肺炎。患者接受更昔洛韦/喷昔洛韦、静脉注射丙种球蛋白和甲泼尼龙治疗,并使用双水平气道正压通气(BiPAP)后症状改善;但停用喷昔洛韦后病情失控,入院22天后死于呼吸衰竭。结论:抗CD19/CD22 CAR-T 治疗后较长时间仍可能发生CMV感染或再激活并引发致死性肺炎,提示需关注CAR-T 输注后免疫抑制相关迟发副作用。
INTRODUCTION: The rapidly developed CAR-T cell therapy has a unique profile of side effects, which perhaps has not been totally realized and understood, especially the late-phase toxicity. CMV is prevalent world-wide and establishes a life-long latency infection. It can lead to life-threatening complications in immunocompromised host, and little is known about CMV disease in patients after CAR-T cell therapy. Here, we report a patient who developed possible CMV-pneumonia three months after anti-CD19 and anti-CD22 CAR-T cell therapy for relapsed B-ALL, contributing to the understanding of severe side-effects mediated by virus infection or reactivation in patients receiving CAR-T cell infusion. CASE PRESENTATION: A 21-year old male patient with relapsed B-ALL received anti-CD19/22 CAR-T cell therapy, and achieved complete remission 2 weeks after the infusion. However, three months later, the patient was hospitalized again with a 10-day history of fever and cough and a 3-day history of palpitations and chest tightness. He was diagnosed with possible CMV pneumonia. Under treatment with antiviral medicine (ganciclovir/penciclovir), intravenous gamma globulin and methylprednisolone and the use of BiPAP ventilator, his symptoms improved, but after removing penciclovir his symptoms went out of control, and the patient died of respiratory failure 22 days after admission. CONCLUSION: CMV infection/reactivation can occur in patients long after receiving anti-CD19/22 CAR-T cell therapy, and induce fatal pneumonia, which reminds us of the late side effects associated with immunosuppression after CAR-T cell infusion.
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