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.
CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
英文原题:Predicting therapy-related myeloid neoplasms after CAR-T with the Clonal Haematopoiesis Risk Score (CHRS).
Predicting therapy-related myeloid neoplasms after CAR-T with the Clonal Haematopoiesis Risk Score (CHRS).
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克隆性造血风险评分(CHRS)旨在预测普通人群中意义未明的克隆性造血(CHIP)/意义未明克隆性血细胞减少(CCUS)进展为髓系肿瘤的速度。CHRS纳入突变类型和变异等位基因频率(VAF)、是否存在单一DNMT3A突变、血细胞减少、年龄、红细胞分布宽度(RDW)和平均红细胞体积(MCV)。我们研究了连续纳入的55例接受CD19靶向CAR-T 细胞治疗患者的克隆性造血:治疗前7%患者存在CHIP,33%存在CCUS。CAR-T 治疗后观察到3例治疗相关髓系肿瘤(t-MN),包括2例MDS和1例AML。仅基线CHRS为中高危的患者发生t-MN。中高危CHRS患者在CAR-T 治疗后前9个月内发生t-MN的风险增加两倍以上(比值比2.89,95%置信区间1.98–4.19,p<0.001)。总体而言,CHRS能够以较好的特异性预测CAR-T 治疗后t-MN的发生。
The clonal haematopoiesis risk score (CHRS) was proposed to predict the rate of progression from clonal haemopoiesis of indeterminate potential (CHIP)/clonal cytopenia with unknown significance (CCUS) to myeloid neoplasms in the general population. CHRS encompasses the type and VAF of the mutation, the presence of a single DNMT3A mutation, cytopenia, age, red cell distribution width (RDW) and mean corpuscular volume (MCV).
We studied clonal haematopoiesis in a cohort of 55 consecutive patients treated with CD19-directed CAR-T cells: CHIP and CCUS were present in 7% and 33% of patients before CAR-T. Three therapy-related myeloid neoplasms (t-MN) were observed after treatment with CAR-T (2 MDS and 1 AML). Only patients with an intermediate-high baseline CHRS developed a t-MN. Patients with an intermediate-high CHRS had more than a twofold increased risk of developing a t-MN within the first 9 months after CAR-T (odds ratio 2. 89, 95% C. I. 1. 98-4. 19, p < 0. 001).
Overall, CHRS was able to predict the occurrence of t-MN after CAR-T with good specificity.
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