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:Progressive Multifocal Leukoencephalopathy After Chimeric Antigen Receptor T-Cell Therapy for Recurrent Non-Hodgkin Lymphoma.
Progressive Multifocal Leukoencephalopathy After Chimeric Antigen Receptor T-Cell Therapy for Recurrent Non-Hodgkin Lymphoma.
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靶向分化簇(CD)19的嵌合抗原受体(CAR)T细胞疗法已对部分复发/难治性非霍奇金淋巴瘤患者的预后产生了变革性影响。我们报告一例难治性大B细胞淋巴瘤患者,在接受CD19靶向CAR-T 细胞疗法后达到完全缓解2年,因进行性失语2周就诊。影像学显示左枕叶脑病变,活检显示进行性多灶性白质脑病的诊断特征。进一步评估显示严重低丙种球蛋白血症和低CD4计数。她接受pembrolizumab和静脉注射免疫球蛋白治疗,导致脑脊液病毒载量下降,但临床无改善,并在就诊8周后死亡。本病例突出表明,CAR-T 细胞疗法后存在严重机会性感染的可能,包括致死性进行性多灶性白质脑病。增强治疗后免疫重建的策略对于进一步利用CAR-T 细胞疗法的独特效力至关重要。
Chimeric antigen receptor (CAR) T-cell therapy targeting cluster of differentiation (CD)19 has had a transformative impact on patient outcomes in a subset of patients with relapsed/refractory non-Hodgkin lymphoma.
We present a patient with refractory large B-cell lymphoma in complete remission for 2 years following treatment with CD19-targeted CAR T-cell therapy, who presented with 2 weeks of progressive aphasia. Imaging revealed a left occipital brain lesion and biopsy demonstrated features diagnostic of progressive multifocal leukoencephalopathy.
Further evaluation revealed severe hypogammaglobulinemia and a low CD4 count. She was treated with pembrolizumab and intravenous immunoglobulin resulting in decreased cerebrospinal fluid viral load without clinical improvement and died 8 weeks after presentation.
This case highlights that there is potential for severe opportunistic infections after CAR T-cell therapy, including fatal progressive multifocal leukoencephalopathy. Strategies to enhance post-treatment immune reconstitution are essential to further harness the unique potency of CAR T-cell therapy.
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