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嵌合抗原受体T细胞(CAR-T)疗法相关的细胞因子释放综合征、神经毒性和噬血细胞性淋巴组织细胞增生症的发病机制及管理策略的最新进展

Latest updates on pathogenesis mechanisms and management strategies for cytokine release syndrome, neurotoxicity, and hemophagocytic lymphohistiocytosis related to CAR-T cell therapies.

作者信息

Wang Xin, He Xiaoyuan, Zhang Tao, Liu Jile, Zhao Mingfeng

机构信息

First Center Clinical College, Tianjin Medical University, Tianjin, 300070, China.

Department of Hematology, Tianjin Thrombosis and Hemostasis Institute, Tianjin First Central Hospital, No.2 Baoshan West Road, Xiqing District, Tianjin, 300192, China.

出版信息

Ann Hematol. 2025 Jun 19. doi: 10.1007/s00277-025-06467-y.


DOI:10.1007/s00277-025-06467-y
PMID:40536724
Abstract

Nowadays, chimeric antigen receptor (CAR) -T cell therapy has shown significant efficacy in treating hematological tumors, with an obvious increase in patient survival rates. However, with the widespread application of CAR-T, the incidence of CAR-T related adverse events has gradually increased, including cytokine release syndrome (CRS), immune effector cell associated neurotoxicity syndrome (ICANS), and hemophagocytic lymphohistiocytosis (HLH). These complications may be life-threatening, so early diagnosis and intervention treatment are crucial for the prognosis of patients. In this review, we first comprehensively summarize the latest insights into the pathogenesis and clinical manifestations of CRS, ICANS, and HLH after CAR-T, with a focus on elaborating on the specific mechanisms and related pathways of the inflammatory storm caused by a large number of cytokines after CAR-T. We also discussed the established prevention and management strategies for the three complications mentioned above, and demonstrated the effectiveness of the treatment by introducing the therapeutic effects of various treatment methods in current clinical or preclinical trials. In addition, we provide a prospective perspective on the measures and modifications currently being studied to mitigate the toxicity associated with CAR-T cell therapy.

摘要

如今,嵌合抗原受体(CAR)-T细胞疗法在治疗血液肿瘤方面已显示出显著疗效,患者生存率明显提高。然而,随着CAR-T的广泛应用,CAR-T相关不良事件的发生率逐渐上升,包括细胞因子释放综合征(CRS)、免疫效应细胞相关神经毒性综合征(ICANS)和噬血细胞性淋巴组织细胞增生症(HLH)。这些并发症可能危及生命,因此早期诊断和干预治疗对患者的预后至关重要。在本综述中,我们首先全面总结了CAR-T后CRS、ICANS和HLH发病机制及临床表现的最新见解,重点阐述了CAR-T后大量细胞因子引发炎症风暴的具体机制及相关途径。我们还讨论了上述三种并发症已确立的预防和管理策略,并通过介绍当前临床或临床前试验中各种治疗方法的治疗效果来证明治疗的有效性。此外,我们对目前正在研究的减轻CAR-T细胞疗法相关毒性的措施和改进方法提供了前瞻性展望。

相似文献

[1]
Latest updates on pathogenesis mechanisms and management strategies for cytokine release syndrome, neurotoxicity, and hemophagocytic lymphohistiocytosis related to CAR-T cell therapies.

Ann Hematol. 2025-6-19

[2]
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[3]
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[6]
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[7]
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[9]
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[10]
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引用本文的文献

[1]
Predictive Power of Baseline [F]FDG PET/CT for Adverse Events in DLBCL Patients Undergoing CAR-T Cell Therapy.

Diagnostics (Basel). 2025-8-13

本文引用的文献

[1]
Efficacy of emapalumab in the management of anti‑CD19 chimeric antigen receptor T‑cell therapy‑associated cytokine release syndrome: A report of two cases.

Oncol Lett. 2024-11-22

[2]
Case report: Rapid resolution of grade IV ICANS after first line intrathecal chemotherapy with methotrexate, cytarabine and dexamethasone.

Front Immunol. 2024

[3]
Bispecific CAR T cell therapy targeting BCMA and CD19 in relapsed/refractory multiple myeloma: a phase I/II trial.

Nat Commun. 2024-4-20

[4]
Multi-centers experience using therapeutic plasma exchange for corticosteroid/tocilizumab-refractory cytokine release syndrome following CAR-T therapy.

Int Immunopharmacol. 2024-3-30

[5]
Patients with Hemophagocytic Lymphohistiocytosis Who Need Intensive Care Can Be Successfully Rescued by Timely Using Etoposide-Based HLH Regimens.

Int J Gen Med. 2024-2-3

[6]
A novel safer CD19CAR with shRNA interference of IFN-γ can reduce multiple cytokine levels without significantly compromising its killing efficacy.

Apoptosis. 2024-4

[7]
The multifaceted roles of GSDME-mediated pyroptosis in cancer: therapeutic strategies and persisting obstacles.

Cell Death Dis. 2023-12-16

[8]
Hemophagocytic lymphohistiocytosis: A disorder of T cell activation, immune regulation, and distinctive immunopathology.

Immunol Rev. 2024-3

[9]
Intrathecal hydrocortisone for treatment of children and young adults with CAR T-cell immune-effector cell-associated neurotoxicity syndrome.

Pediatr Blood Cancer. 2024-1

[10]
Suppression of cytokine release syndrome during CAR-T-cell therapy via a subcutaneously injected interleukin-6-adsorbing hydrogel.

Nat Biomed Eng. 2023-9

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