Background: Cell-free DNA (cfDNA) analysis has become a promising tool for the diagnosis, prognosis, and monitoring of lymphoma cases. Until now, research in this area has mainly focused on aggressive lymphomas, with scanty information from other lymphoma subtypes. Methods: We selected 256 patients diagnosed with lymphomas, including a large variety of B-cell and T-cell non-Hodgkin and Hodgkin lymphomas, and quantified cfDNA from plasma at the time of diagnosis. We further selected 49 large B-cell lymphomas (LBCL) and analyzed cfDNA levels at diagnosis (pre-therapy) and after therapy. In addition, we performed NGS on cfDNA and tissue in this cohort of LBCL. Results: Lymphoma patients showed a statistically significant higher cfDNA concentration than healthy controls (mean 53.0 ng/mL vs. 5.6 ng/mL,p< 0.001). The cfDNA concentration was correlated with lymphoma subtype, lactate dehydrogenase, the International Prognostic Index (IPI) score, Ann Arbor (AA), and B-symptoms. In 49 LBCL cases, the cfDNA concentration decreased after therapy in cases who achieved complete response (CR) and increased in non-responders. The median cfDNA at diagnosis of patients who achieved CR and later relapsed was higher (81.5 ng/mL) compared with levels of those who did not (38.6 ng/mL). A concordance of 84% was observed between NGS results in tumor and cfDNA samples. Higher VAF in cfDNA is correlated with advanced stage and bulky disease. Conclusions: cfDNA analysis can be easily performed in almost all lymphoma cases. The cfDNA concentration correlated with the characteristics of the aggressiveness of the lymphomas and, in LBCL, with the response achieved after therapy. These results support the utility of cfDNA analysis as a complementary tool in the management of lymphoma patients.
背景：游离DNA（cfDNA）分析已成为淋巴瘤诊断、预后评估及病情监测的一种前景广阔的工具。目前该领域研究主要集中于侵袭性淋巴瘤，对其他淋巴瘤亚型的信息掌握有限。方法：我们选取256例确诊淋巴瘤患者（涵盖多种B细胞与T细胞非霍奇金淋巴瘤及霍奇金淋巴瘤亚型），在确诊时对其血浆cfDNA进行定量检测。进一步筛选49例大B细胞淋巴瘤（LBCL）患者，分析治疗前（诊断时）与治疗后的cfDNA水平，并对此LBCL队列的cfDNA与组织样本进行二代测序。结果：淋巴瘤患者cfDNA浓度显著高于健康对照组（均值53.0 ng/mL vs. 5.6 ng/mL，p<0.001）。cfDNA浓度与淋巴瘤亚型、乳酸脱氢酶水平、国际预后指数评分、Ann Arbor分期及B症状具有相关性。在49例LBCL患者中，获得完全缓解者的cfDNA浓度治疗后下降，而无应答者则升高。诊断时获得完全缓解但后续复发患者的cfDNA中位浓度（81.5 ng/mL）高于未复发者（38.6 ng/mL）。肿瘤组织与cfDNA样本的二代测序结果一致性达84%，cfDNA中较高变异等位基因频率与晚期分期及大包块病变相关。结论：cfDNA分析可适用于几乎所有淋巴瘤病例，其浓度与淋巴瘤侵袭性特征相关，在LBCL中与治疗应答程度相关。这些结果支持cfDNA分析作为淋巴瘤患者管理的辅助工具具有重要价值。
Cell-Free DNA as a Biomarker at Diagnosis and Follow-Up in 256 B and T-Cell Lymphomas
肿瘤(癌症)患者之家