{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T20:58:46Z","timestamp":1791233926742,"version":"4.1.0"},"reference-count":78,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2026,3,5]],"date-time":"2026-03-05T00:00:00Z","timestamp":1772668800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancers"],"abstract":"<jats:p>Background\/Objectives: Diffuse large B-cell lymphoma (DLBCL) is the most common subtype of non-Hodgkin lymphoma and remains incurable in approximately 30\u201340% of patients despite advances in immunochemotherapy. Although gene expression profiling has improved risk stratification, there is an ongoing need for non-invasive, cost-effective, and clinically practical biomarkers to identify patients at high risk of treatment resistance or relapse (R\/R). Systemic inflammation plays a pivotal role in DLBCL pathogenesis, impacting both tumor progression and treatment response. The C-reactive protein\u2013albumin\u2013lymphocyte (CALLY) index, integrating markers of inflammation, nutritional status, and immune competence, has demonstrated prognostic relevance in solid tumors; however, its relevance in hematologic malignancies remains unexplored. Methods: We retrospectively analyzed 180 adults with newly diagnosed DLBCL, NOS (not otherwise specified) who received frontline rituximab-based immunochemotherapy (R-CHOP or CHOP-like regimens) between January 2014 and December 2019 at three tertiary centers in Serbia. The median age was 67 years (IQR 59\u201373), and 56.1% were female. Receiver operating characteristic (ROC) analysis determined 6.5 as the optimal CALLY index cut-off (AUC 0.744, 95% CI 0.670\u20130.817; p &lt; 0.001). Results: A low CALLY index (&lt;6.5) was significantly associated with adverse clinical features, including anemia, elevated lactate dehydrogenase and \u03b22-microglobulin, poor ECOG performance status, bulky disease, advanced stage, and unfavorable IPI, R-IPI, and NCCN-IPI scores (all p &lt; 0.001). In contrast, no associations were observed with tumor subtype, immunophenotype, or comorbidities. Furthermore, patients with CALLY &lt;6.5 showed lower overall response rates to treatment (59.6% vs. 85.5%, p &lt; 0.001) and higher relapse rates (21.0% vs. 6.2%, p = 0.014). They also experienced reduced 3- and 5-year overall survival (OS) and event-free survival (EFS) (all p &lt; 0.001). In multivariate analysis, a low CALLY index independently predicted poorer OS (HR 2.04, 95% CI 1.13\u20133.67; p = 0.017) and EFS (HR 1.89, 95% CI 1.13\u20133.14; p = 0.015). In addition, it independently identified patients at risk of relapsed\/refractory (R\/R) disease (OR 2.50, 95% CI 1.02\u201310.10; p = 0.04), outperforming standard prognostic indices. Conclusions: The CALLY index is a simple, low-cost, and widely accessible biomarker that independently predicts prognosis in DLBCL, NOS. It outperforms standard indices in identifying R\/R cases. The CALLY index may enhance risk stratification and guide individualized treatment strategies.<\/jats:p>","DOI":"10.3390\/cancers18050846","type":"journal-article","created":{"date-parts":[[2026,3,5]],"date-time":"2026-03-05T15:29:53Z","timestamp":1772724593000},"page":"846","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Prognostic Value of the CALLY Index in Diffuse Large B-Cell Lymphoma: Linking Inflammation, Nutrition, and Tumor Biology"],"prefix":"10.3390","volume":"18","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4428-7253","authenticated-orcid":false,"given":"Zorica","family":"Cvetkovi\u0107","sequence":"first","affiliation":[{"name":"Department of Hematology, University Hospital Medical Center Zemun, 11080 Belgrade, Serbia"},{"name":"Faculty of Medicine, University of Belgrade, 11000 Belgrade, Serbia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ilija","family":"Bukurecki","sequence":"additional","affiliation":[{"name":"Department of Hematology, University Hospital Medical Center Be\u017eanijska Kosa, 11080 Belgrade, Serbia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4573-2371","authenticated-orcid":false,"given":"Sne\u017eana","family":"Peji\u0107","sequence":"additional","affiliation":[{"name":"Department of Molecular Biology and Endocrinology, Institute of Nuclear Sciences, National Institute of the Republic of Serbia, University of Belgrade, 11000 Belgrade, Serbia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4555-0474","authenticated-orcid":false,"given":"Anica","family":"Divac Pravdi\u0107","sequence":"additional","affiliation":[{"name":"Department of Hematology, University Hospital Medical Center Be\u017eanijska Kosa, 11080 Belgrade, Serbia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Miroslav","family":"Pavlovi\u0107","sequence":"additional","affiliation":[{"name":"Department of Hematology, University Hospital Medical Center Zvezdara, 11000 Belgrade, Serbia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8563-594X","authenticated-orcid":false,"given":"Vesna","family":"Vu\u010di\u0107","sequence":"additional","affiliation":[{"name":"Center of Research Excellence in Nutrition and Metabolism, Institute for Medical Research, National Institute of the Republic of Serbia, University of Belgrade, 11000 Belgrade, Serbia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Olivera","family":"Markovi\u0107","sequence":"additional","affiliation":[{"name":"Faculty of Medicine, University of Belgrade, 11000 Belgrade, Serbia"},{"name":"Department of Hematology, University Hospital Medical Center Zvezdara, 11000 Belgrade, Serbia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,3,5]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"778","DOI":"10.1002\/ijc.33588","article-title":"Cancer statistics for the year 2020: An overview","volume":"149","author":"Ferlay","year":"2021","journal-title":"Int. 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