The proportion of peripheral CD4⁺ cells within CD47⁺ lymphocytes is associated with survival outcomes in diffuse large B-cell lymphoma

Diffuse large B-cell lymphoma (DLBCL) is clinically heterogeneous, and reliable biomarkers for individualized risk stratification remain limited. Peripheral immune phenotypes may reflect systemic immune competence and influence disease progression. Ninety-eight patients with newly diagnosed DLBCL were retrospectively analyzed. The proportion of CD4⁺ cells within CD47⁺ lymphocytes was quantified by flow cytometry at diagnosis. Associations with clinical outcomes were evaluated using Kaplan–Meier and Cox proportional hazards models. Separately, an exploratory contextual analysis of bulk tumor-tissue CD47 messenger RNA (mRNA) expression was performed using the GSE87371 dataset. In this cohort, a lower proportion of CD4⁺ cells within CD47⁺ lymphocytes was associated with inferior progression-free survival (PFS) and overall survival (OS) in the unadjusted Kaplan–Meier analyses (both P < 0.001), whereas its independent prognostic significance was not confirmed after adjustment for the International Prognostic Index (IPI). In a baseline multivariable Cox model, white blood cell (WBC) count, β 2 -microglobulin level, and the proportion of CD4⁺ cells within CD47⁺ lymphocytes were associated with PFS after adjustment for selected baseline covariates. Sensitivity analyses using the marker as a continuous variable and using a median cutoff of 27.35% showed generally consistent directions of association, although the age-adjusted continuous analysis was not statistically significant. Exploratory bulk tumor-tissue transcriptomic analysis did not identify significant associations between tumor CD47 mRNA expression and survival outcomes. A lower proportion of peripheral CD4⁺ cells within CD47⁺ lymphocytes was associated with inferior PFS and OS in unadjusted analyses, but its prognostic independence from established clinical risk factors was not confirmed. This exploratory finding requires prospective multicenter validation before clinical application.