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CAR-T 细胞治疗与病毒特异性 T 淋巴细胞治疗中早期并发症的识别与管理:实用临床参考

英文原题:Recognition and management of early complications in CAR-T cell therapy and virus-specific T-lymphocyte therapy: a practical clinical reference.

PubMed 2026/08/28(内容时间) Front Immunol Q1 · IF 7(JCR 2025)

研究概要

国际公认的标准对细胞免疫效应疗法的早期并发症进行分级。及时识别、早期药物干预和监测对于降低非复发死亡率至关重要。不断扩大的真实世界经验以及治疗前风险分层工具的整合,将继续完善这一快速发展领域中基于证据的实践,最终改善患者结局并降低非复发死亡率。

研究思路结论见上方概要

细胞免疫疗法——包括CAR-T 细胞疗法和病毒特异性T淋巴细胞(VSTs)的过继转移——已改变了难治性血液系统恶性肿瘤和移植后感染性并发症的治疗。目前欧洲药品管理局已批准八种产品,包括七种靶向CD19或BCMA的自体CAR-T产品以及tabelecleucel(Ebvallo),后者是首个获批的异体即用型EBV特异性T细胞产品,用于EBV阳性移植后淋巴增殖性疾病。尽管两者具有临床疗效,但这两种模式均具有不同于传统细胞毒性化疗的独特早期毒性特征。

本综述总结了识别、评估和治疗CAR-T细胞治疗及VST输注后可能出现的早期问题的当前建议。内容:讨论的CAR-T特异性并发症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)、免疫效应细胞相关血液毒性(ICAHT)和免疫效应细胞相关HLH样综合征(IEC-HS)。CRS按ASTCT共识标准分级,并以tocilizumab作为一线药物治疗;激素难治性ICANS最常采用高剂量静脉注射anakinra(最高12 mg/kg/天)治疗,这是目前研究最多的二线选择,尽管支持证据仍主要为观察性研究。ICAHT采用经过验证的EHA/EBMT分级框架进行分类,根据深度和持续时间区分早期(第0-30天)和晚期(第30天后)中性粒细胞减少,管理从预防性G-CSF逐步升级至造血细胞支持,最终选择为异基因HSCT。对于VST,主要的早期并发症为肿瘤 flare 反应(约20%的tabelecleucel受者)、GVHD(使用富集产品时低于5%)、急性输注反应和低级别CRS样细胞因子释放。我们总结了重叠综合征的鉴别诊断、儿科特异性调整、ICU升级标准和临床监测计划。

展开英文摘要原文

BACKGROUND: Cellular immunotherapies-including chimeric antigen receptor T-cell (CAR-T) therapies and adoptive transfer of virus-specific T lymphocytes (VSTs) - have transformed the treatment of refractory hematological malignancies and post-transplant infectious complications. Eight products are currently authorized by the European Medicines Agency, encompassing seven autologous CAR-T products targeting CD19 or BCMA and tabelecleucel (Ebvallo), the first approved allogeneic off-the-shelf EBV-specific T-cell product for EBV-positive post-transplant lymphoproliferative disease. Despite their clinical efficacy, both modalities carry distinct early toxicity profiles that differ from conventional cytotoxic chemotherapy. OBJECTIVE: This review summarizes current recommendations for identifying, assessing, and treating early problems that can occur after CAR-T cell therapy and VST administration. CONTENT: CAR-T-specific complications discussed include cytokine release syndrome (CRS), immune effector cell-associated neurotoxicity syndrome (ICANS), immune effector cell-associated hematotoxicity (ICAHT), and immune effector cell-associated HLH-like syndrome (IEC-HS). CRS is graded by ASTCT consensus criteria and managed with tocilizumab as first-line pharmacological therapy; steroid-refractory ICANS is most commonly treated with high-dose intravenous anakinra (up to 12 mg/kg/day) which is currently the most studied second-line option, although the supporting evidence remains largely observational. ICAHT is classified using the validated EHA/EBMT grading framework, separating early (day 0-30) and late (post-day 30) neutropenia by depth and duration, with management escalating from prophylactic G-CSF through hematopoietic cell boost to allogeneic HSCT as the ultimate option. For VSTs, the principal early complications are tumor flare reaction (in approximately 20% of tabelecleucel recipients), GVHD (below 5% with enriched products), acute infusion reactions, and low-grade CRS-like cytokine release. We summarize a differential diagnosis of overlapping syndromes, pediatric-specific adaptations, ICU escalation criteria, and a clinical monitoring schedule. CONCLUSIONS: Internationally validated criteria grade the early complications of cellular immune effector therapies. Prompt recognition, early pharmacological intervention, and monitoring are essential to minimize non-relapse mortality. Expanding real-world experience and the integration of pre-treatment risk stratification tools will continue to refine evidence-based practice in this rapidly evolving field, ultimately leading to improved patient outcomes and reduced non-relapse mortality rates.

论文信息

作者
Ussowicz M、Jakubczyk E、Wróbel T、Czyż A
第一作者单位
Department of Pediatric Bone Marrow Transplantation, Oncology, and Hematology, Wroclaw Medical University, Wrocław, Poland.Poland
通讯作者单位
Department and Clinic of Hematology, Cellular Therapies, and Internal Medicine, Wroclaw Medical University, Wrocław, Poland.Poland
文献类型
综述
期刊
Frontiers in immunology2026
原文标识
PubMed 42729916 · DOI 10.3389/fimmu.2026.1884854