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
改良 EASIX 评分预测急性髓系白血病患者 CLL1 CAR-T 细胞治疗后的重度 CRS/ICANS
英文原题：Modified EASIX scores predict severe CRS/ICANS in patients with acute myeloid leukemia following CLL1 CAR-T cell therapy.
查看英文原题
Modified EASIX scores predict severe CRS/ICANS in patients with acute myeloid leukemia following CLL1 CAR-T cell therapy.
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中文摘要
靶向CLL1的CAR-T（CAR-T）细胞疗法被认为是治疗急性髓系白血病（AML）患者的有力武器。本研究旨在在更大的队列中评估CLL1 CAR-T 细胞疗法的疗效和毒性，特别关注细胞因子释放综合征（CRS）和免疫效应细胞相关神经毒性综合征（ICANS）。在32例评估疗效的患者中，71.88%（23/32）达到完全缓解，14例患者微小残留病灶检测不到。所有患者均发生CRS，其中8例发生ICANS。分别有11例和2例患者观察到重度CRS和ICANS。
此外，采用CLL1 CAR-T 细胞输注前后测量的内皮激活和应激指数（EASIX）及其衍生物来预测严重并发症。在轻度和重度CRS/ICANS患者之间，淋巴细胞清除前一天（Day BL，P = 0.023）、-1天（P < 0.001）、+1天（P < 0.001）和+3天（P = 0.014）的EASIX评分；Day BL（P = 0.007）、-1天（P < 0.001）、+1天（P < 0.001）和+3天（P < 0.001）的sEASIX评分；以及-1天（P = 0.004）的mEASIX评分均观察到显著差异。
此外，在Day BL（P = 0.004）和-1天（P = 0.044），应答者和非应答者之间的mEASIX评分存在显著差异。
我们的研究结果表明，输注前后评估EASIX/mEASIX/sEASIX评分可作为CLL1 CAR-T 细胞治疗后重度CRS/ICANS和治疗反应的可靠预后指标，有助于医生对潜在严重并发症实施抢先治疗策略，并筛选适合接受CLL1 CAR-T 细胞治疗的患者。EASIX/mEASIX/sEASIX评分可作为CLL1 CAR-T 细胞治疗后严重CRS/ICANS的可靠预后指标。CLL1 CAR-T 细胞输注前的mEASIX评分可有效预测治疗反应。
展开英文摘要原文
Chimeric antigen receptor T (CAR-T) cell therapy targeting CLL1 has been considered a potent weapon for patients with acute myeloid leukemia (AML).
This study aims to evaluate the efficacy and toxicity of CLL1 CAR-T cell therapy in a larger cohort, with particular attention to cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS). Among the 32 patients assessed for efficacy, complete remission occurred in 71. 88% (23/32) of cases and undetectable minimal residual disease in 14 patients. The CRS developed in all patients, with 8 individuals experiencing ICANS. Severe CRS and ICANS were observed in 11 and 2 patients, respectively.
Furthermore, the Endothelial Activation and Stress Index (EASIX) and its derivatives measured before and after CLL1 CAR-T cell infusion were employed for predicting the severe complications. Significant differences were observed in EASIX scores on the day before lymphodepletion (Day BL, P = 0. 023), -1 (P < 0. 001), +1 (P < 0. 001), and +3(P = 0. 014); sEASIX scores on Day BL (P = 0. 007), -1 (P < 0. 001), +1 (P < 0. 001), and +3 (P < 0. 001); and mEASIX score on Day -1 (P = 0. 004) between patients with mild and severe CRS/ICANS.
Additionally, there was a significant difference in mEASIX scores between responders and non-responders on Day BL (P = 0. 004) and Day -1 (P = 0. 044).
Our findings indicate that pre- and post-infusion assessments of EASIX/mEASIX/sEASIX scores serve as reliable prognostic indicators for severe CRS/ICANS and treatment response following CLL1 CAR-T cell therapy, which can assist physicians in implementing preemptive treatment strategies for potential severe complications and screening patients who are suitable candidates for CLL1 CAR-T cell therapy.
EASIX/mEASIX/sEASIX scores serve as reliable prognostic indicators for severe CRS/ICANS following CLL1 CAR-T cell therapy. The preinfusion mEASIX scores of CLL1 CAR-T cells can effectively predict treatment response.
论文信息
- 作者
- Zhao Y、Zhang X、Zhang M、Guo R、Zhang Y、Pu Y、Zhu H、Liu P
- 第一作者单位
- The First Central Clinical College of Tianjin Medical University, Tianjin, 300380, China.China
- 通讯作者单位
- Department of Hematology, Tianjin First Central Hospital, Tianjin, 300380, China. mingfengzhao@sina.com.China
- 期刊
- Annals of hematology2024 Mar
- 原文标识
- PubMed 38214708 · DOI 10.1007/s00277-024-05617-y