Association between serum biomarkers and clinical stage in treatment-naive chronic lymphocytic leukemia

Abstract

Introduction: Chronic lymphocytic leukemia shows significant clinical heterogeneity, highlighting the need for reliable, accessible biomarkers for staging and prognosis, especially in resource-limited settings. This study evaluates the association between inflammatory and nutritional biomarkers and clinical stage in newly diagnosed, treatment-naive patients. Methods: A cross-sectional study enrolled 150 treatment-naive chronic lymphocytic leukemia patients and 150 matched healthy controls at outpatient hematology clinics affiliated with Isfahan University of Medical Sciences (2024-2025). Diagnoses followed International Workshop on chronic lymphocytic leukemia 2018 criteria. Controls were confirmed healthy by peripheral blood counts, smear evaluation, and clinical examination. The Rai staging system was used. Serum biomarkers were measured at diagnosis. Statistical analysis included Analysis of Variance and Kruskal-Wallis tests, and Spearman correlation. Results: Elevated ferritin, beta 2-microglobulin, lactate dehydrogenase and C-reactive protein levels, erythrocyte sedimentation rate, and C-reactive protein-to-albumin ratio correlated significantly with advanced Rai stages (III-IV) (p-value <0.05) reflecting greater tumor burden and systemic inflammation. Conversely, albumin and vitamin D3 levels declined with disease severity. Ferritin and beta 2-microglobulin showed the strongest correlations with clinical stages, reinforcing their prognostic value. Conclusion: Routine biomarkers such as ferritin, beta 2-microglobulin, lactate dehydrogenase, C-reactive protein-to-albumin ratio, and vitamin D3 are strongly associated with clinical stage and disease severity in treatment-naive chronic lymphocytic leukemia patients. Their measurement provides cost-effective, accessible prognostic tools, especially where advanced molecular testing is unavailable. Incorporating these biomarkers into clinical staging may improve early risk stratification and guide management.