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:Durable response of primary cardiac lymphoma after autologous stem cell transplantation and sequential CAR-T therapy: a case report and literature review.
Durable response of primary cardiac lymphoma after autologous stem cell transplantation and sequential CAR-T therapy: a case report and literature review.
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原发性心脏淋巴瘤(PCL)极为罕见且具有侵袭性,局限于心脏和/或心包,诊断与治疗均具重大挑战,既往预后极差。我们报告了首例通过自体造血干细胞移植(ASCT)联合序贯双靶点CD19/20 CAR-T 疗法获得持久完全缓解(CR)的PCL病例。2023年4月,一名55岁女性因胸闷和心包积液就诊。经多种检查和分析,最终通过CT引导下纵隔淋巴结活检确诊。患者接受多种化疗方案,包括利妥昔单抗联合polatuzumab vedotin、R-CHOP、Pola-R-CHP和Pola-R-DA-EPOCH,症状缓解并达到部分缓解。随后接受ASCT,继而进行序贯双靶点CD19/20 CAR-T 治疗。患者约每两个月接受一次PD-1抑制剂信迪利单抗作为维持治疗。CAR-T 输注后3个月患者达到CR,并维持CR长达1年。CAR-T 治疗后患者发生免疫效应细胞相关血液学毒性,通过注射粒细胞集落刺激因子和支持治疗得到控制。本病例显示PCL诊断和治疗存在困难。通过ASCT联合序贯双靶点CD19/20 CAR-T 治疗,患者获得持久CR且毒性可管理。该病例证明这一联合策略治疗高危淋巴瘤的可行性、安全性和潜在疗效。
此外,我们提出一种结构化流程,可能有助于优化类似病例中的CAR-T 临床应用。仍需持续随访和更大规模研究验证这些发现。
Primary cardiac lymphoma (PCL), an exceedingly rare and aggressive extranodal lymphoma confined to the heart and/or pericardium, poses significant diagnostic and therapeutic challenges with a historically dismal prognosis.
We present the first documented case of PCL achieving sustained complete response (CR) through a novel therapeutic approach combining autologous hematopoietic stem cell transplantation (ASCT) with sequential tandem CD19/20 CAR-T therapy. A 55-year-old female presented with chest tightness and pericardial effusion in April 2023. The diagnostic process involved multiple modalities and analyses, culminating in a diagnosis via CT-guided mediastinal lymph node biopsy. The patient underwent several chemotherapy regimens, including combinations of rituximab and polatuzumab vedotin, R-CHOP, Pola-R-CHP, and Pola-R-DA-EPOCH, which led to symptom relief and partial response. Subsequently, ASCT was performed, followed by sequential tandem CD19/20 CAR-T therapy.
As a maintenance treatment, the PD-1 inhibitor sintilimab was administered approximately every two months. The patient achieved CR at month 3 and maintained CR for one year following the CAR-T infusion. Following CAR-T therapy, the patient developed immune effector cell-associated hematologic toxicity, which was managed with granulocyte colony-stimulating factor injection and supportive care.
This case illustrates the difficulties in diagnosing and treating PCL. Through the combination of ASCT and sequential tandem CD19/20 CAR-T therapy, the patient achieved sustained CR with manageable toxicity. This case demonstrates the feasibility, safety, and potential efficacy of this combination strategy in treating high-risk lymphoma.
Moreover, we propose a structured algorithm that may help optimize the clinical implementation of CAR-T therapy in similar cases. Continued follow-up and broader studies are warranted to validate these findings.
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