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儿童及青少年 B 细胞急性淋巴细胞白血病 CAR-T 细胞治疗后细胞因子释放综合征:风暴使树木扎根更深。

Cytokine release syndrome after CAR T-cell therapy for B-cell acute lymphoblastic leukemia in children and young adolescents: storms make trees take deeper roots.

机构信息

Hematology/Oncology Division, CHU Sainte-Justine, Montreal, Quebec, Canada.

Research Center - CHU Sainte-Justine, Montreal, Quebec, Canada.

出版信息

Expert Opin Pharmacother. 2024 Aug;25(11):1497-1506. doi: 10.1080/14656566.2024.2387673. Epub 2024 Aug 6.

DOI:10.1080/14656566.2024.2387673
PMID:39087712
Abstract

INTRODUCTION

Chimeric antigen receptor (CAR) T-cells have revolutionized cancer treatment, showing significant success, including treatment of pediatric B-cell acute lymphoblastic leukemia (B-ALL). Despite their efficacy, cytokine release syndrome (CRS) emerges as a common early adverse effect that can be life threatening in severe cases, resulting from the immune system's targeted activation against tumors.

AREAS COVERED

This review concentrates on CRS in children and young adults undergoing CAR T-cell therapy for B-ALL. It explores CRS pathophysiology, clinical presentation, and incidence, emphasizing the importance of a consensus definition and grading to homogenize the treatment according to the severity of symptoms. We will discuss the standard of care treatment of CRS but also novel approaches. We will highlight the importance of managing CRS without compromising the efficacy of immune cell activation against tumors.

EXPERT OPINION

As CAR T-cell therapy in pediatric B-ALL become increasingly available and used, optimal management of CRS becomes increasingly important. Early recognition and timely management has improved. Further information will aid us to identify optimal timing of tocilizumab and corticosteroids. Continued bench research coupled with clinical studies and biomarker discovery will allow for valuable insights into CRS pathophysiology and patient and/or cell-targeted treatments.

摘要

简介

嵌合抗原受体 (CAR) T 细胞已彻底改变癌症治疗方法,取得了显著成效,包括治疗儿童 B 细胞急性淋巴细胞白血病 (B-ALL)。尽管疗效显著,但细胞因子释放综合征 (CRS) 作为一种常见的早期不良反应,在严重病例中可能危及生命,这是由于免疫系统针对肿瘤的靶向激活。

涵盖领域

本综述集中讨论了接受 CAR T 细胞治疗 B-ALL 的儿童和年轻成人中发生的 CRS。探讨了 CRS 的病理生理学、临床表现和发生率,强调了达成共识定义和分级的重要性,以便根据症状严重程度对治疗进行同质化。我们将讨论 CRS 的标准治疗方法,但也将探讨新方法。我们将强调在不影响针对肿瘤的免疫细胞激活疗效的情况下管理 CRS 的重要性。

专家意见

随着 CAR T 细胞治疗在儿童 B-ALL 中的应用越来越广泛,CRS 的最佳管理变得越来越重要。早期识别和及时管理有所改善。进一步的信息将有助于我们确定托珠单抗和皮质类固醇的最佳时机。持续的基础研究结合临床研究和生物标志物发现,将为 CRS 病理生理学以及针对患者和/或细胞的治疗提供有价值的见解。

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