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.
CAR-T(CAR-T)细胞在血液系统恶性肿瘤中的应用推动了这种免疫治疗形式的显著进展。
CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
英文原题:Management of chimeric antigen receptor T-cell-related toxicity of a patient affected by cytokine release syndrome and immune effector cell-associated neurotoxicity syndrome, followed by an intestinal perforation: a case report.
Management of chimeric antigen receptor T-cell-related toxicity of a patient affected by cytokine release syndrome and immune effector cell-associated neurotoxicity syndrome, followed by an intestinal perforation: a case report.
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本文通过详细的病例介绍,为管理 CAR-T 细胞相关毒性的挑战提供了有价值的见解,并强调了采用多学科方法以提高患者预后和安全性的重要性。需要进一步研究以完善策略并加深对这些复杂治疗相关毒性的理解。
套细胞淋巴瘤是一种具有不同临床行为的多样性B细胞淋巴瘤。治疗复发/难治性套细胞淋巴瘤具有挑战性,Bruton酪氨酸激酶抑制剂被证明有效但无法治愈。在Bruton酪氨酸激酶抑制剂治疗失败后,预后仍然不佳。Brexucabtagene autoleucel是一种获美国食品药品监督管理局和欧洲药品管理局批准的抗CD19CAR-T 细胞疗法,标志着在这一具有挑战性的情况下带来了重大突破和希望。病例介绍:本文分析了一例短期CAR-T 细胞治疗相关毒性的管理,聚焦于一例难治性套细胞淋巴瘤患者的具体病例。该报告强调了CAR-T 细胞治疗的复杂性,并揭示了用于减轻毒性效应的策略。该病例涉及一名59岁白人高加索男性,患有复发性套细胞淋巴瘤,接受了多种治疗,包括自体抗CD19CAR-T 细胞疗法(brexucabtagene autoleucel)。该患者出现了免疫效应细胞相关血液毒性以及细胞因子释放综合征和免疫效应细胞相关神经毒性综合征,需要干预。管理包括托珠单抗、皮质类固醇和阿那白滞素的联合使用,有效缓解了症状。此外,本文还强调了该患者在CAR-T 治疗后发生肠穿孔的病例。尽管胃肠道穿孔与白细胞介素6受体抑制剂之间存在相关性,但该不良事件被归因于患者原有的憩室炎及所施用的免疫抑制药物导致巨细胞病毒再激活。研究强调了CAR-T 细胞疗法的不断演变格局,以及解决这一创新治疗方法相关毒性的重要性。它凸显了阿那白滞素作为免疫效应细胞相关神经毒性综合征的潜在皮质类固醇节约疗法的价值,并提出了进一步研究以优化免疫效应细胞相关血液毒性和相关并发症管理的需求。预防性使用药物以减轻毒性的潜在可能性也值得探索,尽管目前证据尚不充分。
Mantle cell lymphoma is a diverse B-cell lymphoma with varying clinical behaviors. Treating relapsed or refractory mantle cell lymphoma is challenging, with Bruton's tyrosine kinase inhibitors proving effective but not curative. Post-Bruton's tyrosine kinase inhibitor failure, the prognosis remains unfavorable. Brexucabtagene autoleucel, a US Food and Drug and European Medicines Agency-approved anti-CD19 chimeric antigen receptor T-cell therapy, marks a significant breakthrough offering hope in this challenging scenario. CASE PRESENTATION: This article presents an analysis of the management of short-term chimeric antigen receptor T-cell therapy-associated toxicities, focusing on a specific case of a patient with refractory mantle cell lymphoma. The report underscores the complexities of chimeric antigen receptor T-cell treatment and sheds light on strategies employed to mitigate toxic effects. The case involves a white Caucasian 59-year-old male affected by relapsed mantle cell lymphoma who underwent various treatments, including autologous anti-CD19 chimeric antigen receptor T-cell therapy (brexucabtagene autoleucel). The patient experienced immune effector cell-associated hematotoxicity along with cytokine release syndrome and immune effector cell-associated neurotoxicity syndrome, necessitating intervention. The management involved a combination of tocilizumab, corticosteroids, and anakinra, which effectively alleviated symptoms. Additionally, the article highlights the patient's case of intestinal perforation following CAR-T therapy. Although there is a correlation between gastrointestinal perforation and interleukin 6 receptor inhibitors, the adverse event was attributed to the patient's preexisting diverticulitis and the immunosuppressive drugs administered leading to cytomegalovirus reactivation. The study emphasizes the evolving landscape of chimeric antigen receptor T-cell therapy and the significance of addressing toxicities associated with this innovative treatment approach. It underscores the value of anakinra as a potential corticosteroid-sparing therapy for immune effector cell-associated neurotoxicity syndrome and raises the need for further research to optimize the management of immune effector cell-associated hematotoxicity and associated complications. The potential preventive use of drugs to mitigate toxicities also warrants exploration, albeit with the current dearth of evidence.
In conclusion, this article offers valuable insights into the challenges of managing chimeric antigen receptor T-cell-related toxicities through a detailed case presentation and highlights the significance of adopting multidisciplinary approaches to enhance patient outcomes and safety. Further research is needed to refine strategies and advance the understanding of these complex treatment-associated toxicities.
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