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
细胞因子释放综合征对 CAR-T 细胞治疗后持续性血液毒性的临床影响：KyoTox A-Score，一种新型预测模型
英文原题：Clinical Impact of Cytokine Release Syndrome on Prolonged Hematotoxicity after Chimeric Antigen Receptor T Cell Therapy: KyoTox A-Score, a Novel Prediction Model.
查看英文原题
Clinical Impact of Cytokine Release Syndrome on Prolonged Hematotoxicity after Chimeric Antigen Receptor T Cell Therapy: KyoTox A-Score, a Novel Prediction Model.
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中文摘要
持续性血液毒性是CAR-T 细胞治疗（CAR-T）后最常见的长期不良事件。为了评估CAR-T 输注后炎症状态对持续性血细胞减少的影响，我们开展了一项单中心回顾性研究，分析了接受CAR-T 治疗的B细胞淋巴瘤患者。在输注后90天可分析的90例患者中，持续性中性粒细胞减少的累积发生率为57.5%，贫血为36.7%，血小板减少为49.8%。发生细胞因子释放综合征（CRS）的患者持续性血细胞减少的发生率显著更高、持续时间更长。
此外，我们发现在1级CRS患者中，CRS相关症状持续时间较长（>5天；改良CRS分级[m-CRS]中的1b级）的患者，其持续性血细胞减少的发生率显著高于CRS相关症状在5天内缓解的患者（m-CRS 1a级），且持续时间更长。多因素分析显示，较高的m-CRS分级（1b级或2级；风险比[HR]，2.42）、较高的CRP峰值（10 mg/dL；HR，1.66）、CRP升高持续时间较长（10天；HR，1.83）以及血清无机磷浓度下降（较基线下降 30%；HR，1.95）与持续性中性粒细胞减少以及贫血和血小板减少的累积发生率显著升高相关。利用这些因素，我们开发了一种新的持续性血液毒性预测评分模型——KyoTox a-score，该模型能够成功地对血细胞减少的发生率和持续时间进行分层，且独立于现有基于淋巴细胞清除时实验室数据的模型CAR-HEMATOTOX。
因此，这一新开发的CAR-T 后炎症依赖性评分对于预测持续性血液毒性是准确且有用的。
展开英文摘要原文
Prolonged hematotoxicity is the most common long-term adverse event in chimeric antigen receptor T cell therapy (CAR-T). To evaluate the impact on prolonged cytopenia of inflammatory status after CAR T infusion, we performed a single-center retrospective study and analyzed patients with B cell lymphomas after CAR-T.
Among 90 patients analyzed at 90 days after infusion, the cumulative incidence was 57. 5% for prolonged neutropenia, 36. 7% for anemia, and 49. 8% for thrombocytopenia. Patients who experienced cytokine release syndrome (CRS) had significantly higher incidence and longer duration of prolonged cytopenia.
In addition, we found that among patients with grade 1 CRS, those with a longer duration of CRS-related symptoms (>5 days; grade 1b in modified CRS grading [m-CRS]) had a significantly higher incidence and longer duration of prolonged cytopenia than those whose CRS-related symptoms resolved within 5 days (grade 1a m-CRS). Multivariate analysis revealed that a higher m-CRS grade (grade 1b or 2; hazard ratio [HR], 2. 42), higher peak CRP ( 10 mg/dL; HR, 1. 66), longer duration of elevated CRP ( 10 days; HR, 1.
83), and a decrease in serum inorganic phosphorus concentration ( 30% from baseline; HR, 1. 95) were associated with significantly higher cumulative incidence of prolonged neutropenia, as well as anemia and thrombocytopenia. Using these factors, we developed a new predictive scoring model for prolonged hematotoxicity, the KyoTox a-score, which can successfully stratify the incidence and duration of cytopenia independent of the existing model, CAR-HEMATOTOX, which is based on laboratory data at lymphodepletion.
Thus, this newly developed post-CAR-T inflammation-dependent score is accurate and useful for predicting prolonged hematotoxicity.
论文信息
- 作者
- Nakamura N、Jo T、Arai Y、Kitawaki T、Nishikori M、Mizumoto C、Kanda J、Yamashita K
- 第一作者单位
- Department of Hematology and Oncology, Kyoto University Hospital, Kyoto, Japan.Japan
- 通讯作者单位
- Department of Hematology and Oncology, Kyoto University Hospital, Kyoto, Japan; Center for Research and Application of Cellular Therapy, Kyoto University Hospital, Kyoto, Japan. Electronic address: ysykrai@kuhp.kyoto-u.ac.jp.Japan
- 文献类型
- 非美国政府资助研究
- 期刊
- Transplantation and cellular therapy2024 Apr
- 原文标识
- PubMed 38281589 · DOI 10.1016/j.jtct.2024.01.073