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动态 ctDNA 监测:预测 CAR-T 细胞治疗患者应答的主要工具

英文原题:Dynamic ctDNA Monitoring: A Primary Tool Predictive of Response in a Patient on CAR-T Cell Therapy.

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Dynamic ctDNA Monitoring: A Primary Tool Predictive of Response in a Patient on CAR-T Cell Therapy.

PubMed 2025/05/25(内容时间) Int J Lab Hematol Q3 · IF 2.2(JCR 2025)

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研究概要

该病例表明,动态 ctDNA 分析可反映早期分子学反应,早于影像学确认。

中文摘要

引言:动态监测循环肿瘤DNA(ctDNA)为追踪恶性肿瘤治疗应答提供了一种无创方法。虽然其在实体瘤中的应用已较成熟,但在淋巴瘤中的作用,尤其是预测CAR-T 细胞疗法应答方面,仍研究不足;印度相关经验尤为有限。本病例强调ctDNA可能成为预测接受CAR-T 疗法的复发/难治性弥漫性大B细胞淋巴瘤(DLBCL)应答的生物标志物。病例报告:一名48岁男性患转化型滤泡性淋巴瘤进展为DLBCL,对R-CHOP和BR方案均耐药,随后接受抗CD19 CAR-T 细胞疗法。基线血浆ctDNA分析发现TP53 p.E286K突变,变异等位基因频率(VAF)为1.3%。连续监测显示,该突变在4周时降至0.4%,输注后8周完全清除;这与PET-CT上的代谢完全缓解一致。未观察到共现突变。讨论:本病例说明,动态ctDNA谱可反映早期分子学应答,并先于影像学确认。既有文献提示,CAR-T 治疗后早期ctDNA转阴与结局改善相关。这是印度首例使用经验证的自制NGS ctDNA检测方法纵向追踪CAR-T 应答的报告。纳入ctDNA指导的监测或可完善应答评估并减少不必要的影像检查,从而在资源受限环境中优化治疗结局。

展开英文摘要原文

INTRODUCTION: Dynamic monitoring of circulating tumor DNA (ctDNA) offers a non-invasive method to track treatment response in malignancies. While well-established in solid tumors, its role in lymphomas, especially in predicting response to CAR-T cell therapy, remains underexplored-more so in the Indian context. This case highlights ctDNA as a potential predictive biomarker in relapsed/refractory DLBCL undergoing CAR-T therapy. CASE REPORT: A 48-year-old male with transformed follicular lymphoma to DLBCL, refractory to R-CHOP and BR, was treated with anti-CD19 CAR-T cell therapy. Baseline ctDNA profiling from plasma revealed a TP53 p. E286K mutation at 1. 3% VAF. Serial monitoring showed a decline to 0.

4% at four weeks and complete clearance at eight weeks post-infusion, correlating with metabolic complete response on PET-CT. No co-occurring mutations were observed. DISCUSSION: This case illustrates how dynamic ctDNA profiling can reflect early molecular response, preceding radiological confirmation.

Existing literature suggests that early ctDNA negativity post-CAR-T correlates with improved outcomes. This is the first reported Indian case employing a validated, homebrew NGS-based ctDNA assay to longitudinally track CAR-T response. Incorporating ctDNA-guided surveillance may refine response assessment and reduce unnecessary imaging, optimizing outcomes in resource-constrained settings.

论文信息

作者
Rahul B、Shrinidhi N、Ishita S、Kumar Nikhil M、Chitresh Y、Anusha S、Darshan T、Kanika V
第一作者单位
Principal Director, Hematology and BMT, Fortis Memorial Research Institute, Gurugram, India.India
通讯作者单位
Hematology and BMT, Fortis Memorial Research Institute, Gurugram, India.India
文献类型
病例报告 · 读者来信
期刊
International journal of laboratory hematology2025 Aug
原文标识
PubMed 40415376 · DOI 10.1111/ijlh.14503