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血液吸附作为 CAR-T 细胞治疗相关严重毒性的支持策略:一项病例系列

英文原题:Hemoadsorption as a Supportive Strategy for Severe Toxicity Associated With Chimeric Antigen Receptor T-Cell Therapy: A Case Series.

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Hemoadsorption as a Supportive Strategy for Severe Toxicity Associated With Chimeric Antigen Receptor T-Cell Therapy: A Case Series.

PubMed 2025/04/03(内容时间) Kidney Med Q1 · IF 4.1(JCR 2025)

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研究概要

基于血液吸附的策略在缓解接受 CAR-T 治疗并出现早期严重毒性的血液肿瘤患者的炎症和改善血流动力学方面是安全有效的。

研究思路结论见上方概要

描述使用血液吸附进行体外血液净化在管理CAR-T 细胞治疗后严重并发症中的应用及效果。

回顾性病例系列分析。机构:单一机构的血液科和重症监护室。患者:2021年至2023年间接受CAR-T 治疗、发生严重毒性、并根据临床指征接受血液吸附治疗的血液肿瘤患者。

48例患者中,4例(8.3%)接受了体外血液净化治疗:3例为弥漫大B细胞淋巴瘤,1例为套细胞淋巴瘤。这些患者在CAR-T 输注后血清白细胞介素-6和铁蛋白水平迅速升高,进展为伴有血流动力学不稳定的重度细胞因子释放综合征和多器官毒性。尽管在托珠单抗治疗失败后使用了皮质类固醇和阿那白滞素挽救治疗,但由于临床状况迅速恶化,在CAR-T 输注后平均5.2 1.7天开始使用血液吸附进行体外血液净化。治疗采用连续性静脉-静脉血液透析滤过,使用AN69ST血滤器和CytoSorb吸附柱。1例患者在血液净化开始后1天死亡,原因为合并心肌病进展为多器官衰竭。在3例存活患者中,白细胞介素-6水平显著下降(从-18%至-95%),细胞因子释放综合征缓解,血管活性药物支持减少。未观察到治疗相关并发症。局限性:样本量小、回顾性设计、缺乏预先设定的血液吸附治疗方案。

展开英文摘要原文

To describe the use and effects of extracorporeal blood purification with hemoadsorption in managing severe complications after treatment with chimeric antigen receptor T-cells (CAR-T). STUDY DESIGN: Retrospective analysis of a case series. SETTING & PARTICIPANTS: Hematological department and intensive care unit from a single institution. Patients with hematological cancer who underwent CAR-T therapy between 2021 and 2023, developed severe toxicity, and were treated with hemoadsorption based on clinical indications.

Of 48 patients, extracorporeal blood purification was prescribed to 4 (8.3%): 3 with diffuse large B-cell lymphoma and 1 with mantle cell lymphoma. These patients experienced rapid increases in serum interleukin-6 and ferritin levels after CAR-T infusion, which progressed to severe cytokine release syndrome with hemodynamic instability and multiple-organ toxicity. Despite corticosteroid and anakinra rescue therapy after tocilizumab failure, extracorporeal blood purification with hemoadsorption was initiated at a mean of 5.2 1.7 days following CAR-T infusion due to rapid clinical deterioration. The treatment was performed using continuous venovenous hemodiafiltration with an AN69ST hemofilter and a CytoSorb cartridge. One patient died 1 day after the initiation of blood purification because of concomitant cardiomyopathy progressing to multiple-organ failure. In the 3 surviving patients, interleukin-6 levels significantly decreased (from -18% to -95%), cytokine release syndrome resolved, and vasoactive support was reduced. Treatment-related complications were not observed. LIMITATIONS: Small sample size, retrospective design, and lack of a predefined hemoadsorption therapy protocol.

A strategy based on hemoadsorption was safe and effective in mitigating inflammation and improving hemodynamics in patients with hematological cancer treated with CAR-T therapy who developed early severe toxicity. Chimeric antigen receptor T-cell (CAR-T) therapy may improve remission rates and survival in hematological cancers but can lead to severe side effects, including cytokine release syndrome (CRS). CRS is characterized by systemic inflammation and multiorgan toxicity and is often associated with poor outcomes. Although pharmacological treatments are available, some cases remain refractory. In this study, we share our experience with hemoadsorption as a supportive therapy for severe CRS in CAR-T recipients. Of the 4 patients treated, 3 experienced CRS resolution with reduced inflammation and improved hemodynamic stability, without treatment-related complications. These findings highlight hemoadsorption as a promising adjunctive therapy to pharmacological treatments for managing severe CAR-T toxicities. Further research is needed to confirm these results.

论文信息

作者
Esposito P、Gambella M、Russo E、Raiola AM、Beltrametti E、Conti N、Porcile E、Bianzina S
第一作者单位
Department of Internal Medicine (DIMI), University of Genova, Genova, Italy.Italy
通讯作者单位
Unit of Hematology and Cellular Therapy, IRCCS Ospedale Policlinico San Martino, Genova, Italy.Italy
期刊
Kidney medicine2025 Jun
原文标识
PubMed 40510619 · DOI 10.1016/j.xkme.2025.101001