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

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; I = 84%) and inferior PFS (HR 1.51, 95% CI 1.01-2.27; I = 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; I = 15%) and PFS (HR 1.81, 95% CI 1.33-2.46; I = 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.