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CD19嵌合抗原受体T细胞疗法急性期出现的多个小肠溃疡伴穿孔,可能与托珠单抗的使用有关。

Multiple Ulcers with Perforations of the Small Intestine in the Acute Phase of CD19 Chimeric Antigen Receptor T-cell Therapy Possibly Associated with Tocilizumab Administration.

作者信息

Masuda Yasutaka, Honda Akira, Yasunaga Yoichi, Kurokawa Mineo

机构信息

Department of Hematology and Oncology, Graduate School of Medicine, The University of Tokyo, Japan.

Department of Pathology, The University of Tokyo Hospital, Japan.

出版信息

Intern Med. 2025;64(3):435-438. doi: 10.2169/internalmedicine.3815-24. Epub 2025 Feb 1.

DOI:10.2169/internalmedicine.3815-24
PMID:39894508
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11867749/
Abstract

CD19 chimeric antigen receptor (CAR) T-cell therapy is associated with potentially life-threatening immunological toxicities. We herein report an 81-year-old woman who experienced multiple perforations in the small intestine 8 days after tisagenlecleucel infusion for relapsed and refractory follicular lymphoma with no gastrointestinal involvement. A pathological examination of the resected small intestine revealed multiple ulcers that formed after resection but without lymphoma involvement. Based on these findings, tocilizumab used for cytokine release syndrome was considered to be associated with these lesions. This case illustrates a previously undescribed but serious sequela of CAR T-cell therapy, calling for relevant personnel to be vigilant about gastrointestinal symptoms.

摘要

CD19嵌合抗原受体(CAR)T细胞疗法与潜在的危及生命的免疫毒性相关。我们在此报告一名81岁女性,她在接受替沙格韦单抗输注治疗复发难治性滤泡性淋巴瘤(无胃肠道受累)8天后,小肠出现多处穿孔。对切除的小肠进行病理检查发现,切除后形成了多处溃疡,但无淋巴瘤累及。基于这些发现,用于细胞因子释放综合征的托珠单抗被认为与这些病变有关。该病例说明了CAR T细胞疗法以前未被描述但严重的后遗症,呼吁相关人员对胃肠道症状保持警惕。

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本文引用的文献

1
Tocilizumab-induced mucosal injury in the terminal ileum mimicking intestinal Behçet's disease: A case report.托珠单抗诱导的回肠末段黏膜损伤模拟肠贝赫切特病:病例报告。
Medicine (Baltimore). 2023 Jun 23;102(25):e34118. doi: 10.1097/MD.0000000000034118.
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Long-term outcomes following CAR T cell therapy: what we know so far.嵌合抗原受体 T 细胞疗法治疗后的长期结果:目前我们所了解的情况。
Nat Rev Clin Oncol. 2023 Jun;20(6):359-371. doi: 10.1038/s41571-023-00754-1. Epub 2023 Apr 13.
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Post-Marketing Surveillance of CAR-T-Cell Therapies: Analysis of the FDA Adverse Event Reporting System (FAERS) Database.
上市后 CAR-T 细胞疗法监测:FDA 不良事件报告系统(FAERS)数据库分析。
Drug Saf. 2022 Aug;45(8):891-908. doi: 10.1007/s40264-022-01194-z. Epub 2022 Jul 12.
4
Tocilizumab-Associated Small Bowel Perforation in a Young Patient With Rheumatoid Arthritis: A Lesson to Remember During COVID-19 Pandemic.一名年轻类风湿关节炎患者发生托珠单抗相关的小肠穿孔:COVID-19大流行期间的一个警示案例
J Med Cases. 2022 Mar;13(3):135-139. doi: 10.14740/jmc3902. Epub 2022 Mar 5.
5
Management of adults and children receiving CAR T-cell therapy: 2021 best practice recommendations of the European Society for Blood and Marrow Transplantation (EBMT) and the Joint Accreditation Committee of ISCT and EBMT (JACIE) and the European Haematology Association (EHA).成人和儿童接受嵌合抗原受体 T 细胞(CAR T)疗法的管理:欧洲血液和骨髓移植学会(EBMT)、国际干细胞治疗认证委员会和 EBMT(JACIE)联合认证委员会以及欧洲血液学协会(EHA)的 2021 年最佳实践建议。
Ann Oncol. 2022 Mar;33(3):259-275. doi: 10.1016/j.annonc.2021.12.003. Epub 2021 Dec 16.
6
A Rare Case of Rheumatoid Arthritis with Tocilizumab-induced Intestinal Mucosal Injury.托珠单抗致类风湿关节炎患者肠道黏膜损伤 1 例罕见报告
Intern Med. 2022 Apr 1;61(7):1011-1014. doi: 10.2169/internalmedicine.8031-21. Epub 2021 Sep 18.
7
Outcomes of CD19 Chimeric Antigen Receptor T Cell Therapy in Patients with Gastrointestinal Tract Involvement of Large B Cell Lymphoma.嵌合抗原受体 T 细胞疗法治疗胃肠道受累的大 B 细胞淋巴瘤患者的结果。
Transplant Cell Ther. 2021 Sep;27(9):768.e1-768.e6. doi: 10.1016/j.jtct.2021.05.018. Epub 2021 May 30.
8
Cytokine release syndrome and associated neurotoxicity in cancer immunotherapy.细胞因子释放综合征及癌症免疫治疗相关神经毒性
Nat Rev Immunol. 2022 Feb;22(2):85-96. doi: 10.1038/s41577-021-00547-6. Epub 2021 May 17.
9
Risk of diverticulitis and gastrointestinal perforation in rheumatoid arthritis treated with tocilizumab compared to rituximab or abatacept.与利妥昔单抗或阿巴西普相比,托珠单抗治疗类风湿关节炎时发生憩室炎和胃肠道穿孔的风险。
Rheumatology (Oxford). 2022 Mar 2;61(3):953-962. doi: 10.1093/rheumatology/keab438.
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Potential role of tocilizumab in severe gastrointestinal barrier damage after CAR T-cell therapy.托珠单抗在 CAR-T 细胞治疗后严重胃肠道屏障损伤中的潜在作用。
J Microbiol Immunol Infect. 2021 Apr;54(2):327-330. doi: 10.1016/j.jmii.2021.02.006. Epub 2021 Feb 27.