{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,2]],"date-time":"2026-11-02T21:17:27Z","timestamp":1793654247753,"version":"4.5.1"},"reference-count":31,"publisher":"American Society of Hematology","issue":"7","content-domain":{"domain":["ashpublications.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2025,4,8]]},"abstract":"<jats:sec>\n                    <jats:title>Abstract<\/jats:title>\n                    <jats:p>Circulating tumor DNA (ctDNA) levels can help predict outcomes in diffuse large B-cell lymphoma (DLBCL), but its integration with DLBCL molecular clusters remains unexplored. Using the LymphGen tool in 77 DLBCL cases with both ctDNA and tissue biopsy, a 95.8% concordance rate in molecular cluster assignment was observed, showing the reproducibility of molecular clustering on ctDNA. A multicenter, prospective cohort of 166 patients with newly diagnosed DLBCL was analyzed for ctDNA levels and molecular clusters using cancer personalized profiling by deep sequencing. Patients with ctDNA levels of &amp;lt;2.5\u00a0log10 haploid genome equivalents (hGE)\/mL had a 4-year progression-free survival (PFS) and overall survival (OS) of 71.7% and 85.7%, respectively, compared with 50.3% and 61.0% for those with higher ctDNA levels (P\u00a0=\u00a0.0018 and P\u00a0=\u00a0.0017). Recursive partitioning showed that patients with ctDNA levels of \u22652.5 log10 hGE\/mL were further stratified by clusters ST2\/BN2. In this group, ST2\/BN2 patients associated with a favorable outcome with a 4-year PFS and OS of 87.5% and 100%, respectively, compared to 38.0% and 47.1% for other clusters (P\u00a0=\u00a0.003 and P\u00a0=\u00a0.001). Combining ctDNA levels and ST2\/BN2 clusters improved outcome prediction. Low-risk patients (n\u00a0=\u00a051), characterized by ctDNA levels of &amp;lt;2.5 log10 hGE\/mL and\/or BN2\/ST2 cluster, had a 4-year PFS and OS of 75.3% and 87.8%, respectively. High-risk patients (n\u00a0=\u00a0115), with ctDNA levels of \u22652.5 log10 hGE\/mL and no BN2\/ST2 cluster, had a 4-year PFS and OS of 38.0% and 47.1%, respectively. Adding cluster assignment to ctDNA levels improved the model\u2019s C statistics (0.63 vs 0.59 for PFS; 0.68 vs 0.63 for OS). Liquid biopsy thus provides a multilayered approach for outcome prediction in DLBCL.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1182\/bloodadvances.2024014136","type":"journal-article","created":{"date-parts":[[2025,1,18]],"date-time":"2025-01-18T09:20:56Z","timestamp":1737192056000},"page":"1692-1701","update-policy":"https:\/\/doi.org\/10.1182\/blood.2019cm0000","source":"Crossref","is-referenced-by-count":24,"title":["Molecular clustering on ctDNA improves the prognostic stratification of patients with DLBCL compared with ctDNA levels"],"prefix":"10.1182","volume":"9","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7393-1138","authenticated-orcid":false,"given":"Riccardo","family":"Moia","sequence":"first","affiliation":[{"name":"1Division of Hematology, Department of Translational Medicine, Universit\u00e0 del Piemonte Orientale, Novara, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-5875-8508","authenticated-orcid":false,"given":"Donatella","family":"Talotta","sequence":"additional","affiliation":[{"name":"1Division of Hematology, Department of Translational Medicine, Universit\u00e0 del Piemonte Orientale, Novara, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lodovico","family":"Terzi Di Bergamo","sequence":"additional","affiliation":[{"name":"2Laboratory of Experimental Hematology, Institute of Oncology Research, Bellinzona, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0048-3845","authenticated-orcid":false,"given":"Mohammad","family":"Almasri","sequence":"additional","affiliation":[{"name":"1Division of Hematology, Department of Translational Medicine, Universit\u00e0 del Piemonte Orientale, Novara, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Riccardo","family":"Dondolin","sequence":"additional","affiliation":[{"name":"1Division of Hematology, Department of Translational Medicine, Universit\u00e0 del Piemonte Orientale, Novara, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matin","family":"Salehi","sequence":"additional","affiliation":[{"name":"2Laboratory of Experimental Hematology, Institute of Oncology Research, Bellinzona, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8199-4593","authenticated-orcid":false,"given":"Chiara","family":"Cosentino","sequence":"additional","affiliation":[{"name":"1Division of Hematology, Department of Translational Medicine, Universit\u00e0 del Piemonte Orientale, Novara, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8027-2430","authenticated-orcid":false,"given":"Roberta","family":"Soscia","sequence":"additional","affiliation":[{"name":"3Institute of Hematology, Hematology Unit, Department of Translational and Precision Medicine, Sapienza University, Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Irene","family":"Della Starza","sequence":"additional","affiliation":[{"name":"3Institute of Hematology, Hematology Unit, Department of Translational and Precision Medicine, Sapienza University, Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-9938-0396","authenticated-orcid":false,"given":"Alessio","family":"Bruscaggin","sequence":"additional","affiliation":[{"name":"2Laboratory of Experimental Hematology, Institute of Oncology Research, Bellinzona, 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