Preprint Article Version 1 Preserved in Portico This version is not peer-reviewed

Cell‐Free DNA as a Biomarker at Diagnosis and Follow up in 256 B and T Cell Lymphomas

Version 1 : Received: 11 December 2023 / Approved: 11 December 2023 / Online: 11 December 2023 (15:59:03 CET)

A peer-reviewed article of this Preprint also exists.

Diez-Feijóo, R.; Andrade-Campos, M.; Gibert, J.; Sánchez-González, B.; Fernández-Ibarrondo, L.; Fernández-Rodríguez, C.; Garcia-Gisbert, N.; Camacho, L.; Lafuente, M.; Vázquez, I.; Colomo, L.; Salar, A.; Bellosillo, B. Cell-Free DNA as a Biomarker at Diagnosis and Follow-Up in 256 B and T-Cell Lymphomas. Cancers 2024, 16, 321. Diez-Feijóo, R.; Andrade-Campos, M.; Gibert, J.; Sánchez-González, B.; Fernández-Ibarrondo, L.; Fernández-Rodríguez, C.; Garcia-Gisbert, N.; Camacho, L.; Lafuente, M.; Vázquez, I.; Colomo, L.; Salar, A.; Bellosillo, B. Cell-Free DNA as a Biomarker at Diagnosis and Follow-Up in 256 B and T-Cell Lymphomas. Cancers 2024, 16, 321.

Abstract

Background: Cell-free DNA (cfDNA) analysis has become a promising tool for diagnosis, prognosis and monitoring of lymphoma cases. Until now, research in this area has mainly focused in 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 in 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 correlated with lymphoma subtype, lactate dehydrogenase, 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 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 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.

Keywords

cfDNA; Liquid biopsy; Lymphoma; monitoring

Subject

Medicine and Pharmacology, Hematology

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