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:Longitudinal ctDNA tracking by low-pass whole-genome sequencing predicts CAR-T outcomes in B-cell lymphomas.
Longitudinal ctDNA tracking by low-pass whole-genome sequencing predicts CAR-T outcomes in B-cell lymphomas.
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目前用于监测接受 CAR-T 治疗的复发/难治性 B 细胞淋巴瘤的 PET/CT 往往缺乏特异性。我们评估了 11 例接受 axicabtagene ciloleucel 治疗的 B 细胞淋巴瘤患者循环肿瘤 DNA(ctDNA)的纵向低深度全基因组测序(LP-WGS),以评估治疗反应和预后。我们发现,较低的基线肿瘤分数与完全缓解(CR)相关,而基线或输注后 1 个月时 ctDNA 阳性显著预测较差的生存结局。将 ctDNA 与 PET/CT 联合可优化风险分层,比单独影像学更准确地识别高危患者。此外,特定基因组特征,如 17p 缺失和高拷贝数变异负荷,与不良预后相关。我们得出结论,ctDNA 的 LP-WGS 有望作为 PET/CT 的补充工具,用于 CAR-T 治疗的 B 细胞淋巴瘤的反应评估和风险分层,凸显其在指导淋巴瘤诊疗中个体化临床管理方面的潜力。
Current PET/CT monitoring for relapsed/refractory B-cell lymphomas treated with CAR-T therapy often lacks specificity.
We evaluated longitudinal low-pass whole-genome sequencing (LP-WGS) of circulating tumor DNA (ctDNA) in 11 patients with B-cell lymphoma receiving axicabtagene ciloleucel to assess treatment response and prognosis.
We found that lower baseline tumor fraction correlated with complete remission (CR), and ctDNA positivity at baseline or 1-month post-infusion significantly predicted inferior survival outcomes. Combining ctDNA with PET/CT refined risk stratification, distinguishing high-risk patients more accurately than imaging alone.
Furthermore, specific genomic features, such as 17p deletion and high copy number variation burden, were associated with poor prognosis.
We conclude that LP-WGS of ctDNA shows promise as a complementary tool to PET/CT for response evaluation and risk stratification in CAR-T-treated B-cell lymphomas, highlighting its potential to guide personalized clinical management in lymphoma care.
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