Prognostic relevance of the neutrophil/lymphocyte ratio in diffuse large B-cell lymphoma: a systematic review and meta-analysis and dose–response evidence

Pichardo-Rodriguez R.; Vela-Ruiz J.M.; Villela L.; Torres Viera M.-A.; Beltran-Garate B.; Ruiz-Franco O.; Munayco-Guillén F.; Malpica L.; Castillo J.J. · Leukemia and Lymphoma (2025) · DOI: 10.1080/10428194.2025.2566980

Resumen

Diffuse large B-cell lymphoma exhibits substantial prognostic heterogeneity, and inflammatory biomarkers such as the neutrophil-to-lymphocyte ratio (NLR) may provide complementary risk information to established clinical scores. We conducted a systematic review and meta-analysis including 20 studies with 5,770 patients for overall survival (OS) and 3,612 for progression-free survival (PFS). Higher pretreatment NLR was associated with inferior OS (HR 1.47, 95% CI 1.20–1.80; I² = 84%) and inferior PFS (HR 1.51, 95% CI 1.01–2.27; I² = 0%). Regionally, the OS association was strongest in European cohorts (HR 2.01, 95% CI 1.5–2.5), followed by Latin-American studies (HR 1.63, 95% CI 1.2–2.1), and was not evident in Asian series (HR 1.13, 95% CI 0.8–1.5). Using a cutoff NLR ≥ 4 strengthened associations for both OS (HR 1.61, 95% CI 1.39–1.87; I² = 15%) and PFS (HR 1.81, 95% CI 1.33–2.46; I² = 51%), whereas lower cutoffs were not consistently prognostic. Sensitivity analyses modestly reduced heterogeneity without altering conclusions. Publication-bias tests (Egger’s test; trim-and-fill) attenuated pooled effects (OS HR 1.06; PFS HR 1.14), supporting cautious interpretation. In individual-participant data from 1,137 patients treated mainly with R-CHOP (median follow-up 50 months), baseline NLR showed a nonlinear dose-response association with OS; risk increased 39% across NLR 2.0–5.9 (HR 1.39; c-index 0.589). Clinically, NLR is inexpensive, universally available, and may refine risk stratification alongside IPI/NCCN-IPI particularly in resource-limited settings. Prospective, region-specific validation and standardization of an operational threshold (e.g. NLR ≥ 4) should be prioritized to enable clinical adoption.

Instituciones: Universidad Nacional Mayor de San Marcos; Universidad Ricardo Palma; Universidad San Ignacio de Loyola