Neutrophil-to-lymphocyte ratio as a prognostic indicator of mortality in Polycythemia Vera: insights from a prospective cohort analysis

Abstract

We analyzed the neutrophil-to-lymphocyte ratio (NLR) in 1508 patients with PV and found that those with an NLR ≥ 5 were generally older, had a longer disease history, and had higher cardiovascular risk factors, more arterial thrombosis, and more aggressive blood counts, indicating a more proliferative disease. NLR was an accurate predictor of mortality, with patients with NLR ≥ 5 having significantly worse overall survival and more than twice the mortality rate compared to those with NLR < 5. Multivariable models confirmed that increasing age, previous venous thrombosis and NLR ≥ 5 were strong predictors of death, further influenced by cardiovascular risk factors. We examined the interaction between NLR and the number of cardiovascular risk factors and found a progressive trend of increased mortality risk for NLR values ≥ 5 in addition to the presence of more than one risk factor. In conclusion, patients with NLR ≥ 5 require careful monitoring and management of cardiovascular risk factors because they increase mortality when associated with progressive levels of NLR.

Fig. 1. Generalized additive models (GAMs) for the prediction of death.

The figure reports GAMs by absolute neutrophils (A), lymphocytes (B) and their ratio NLR (C). The effect of neutrophils, lymphocytes and their ratio on the risk of death was analyzed on a continuous scale using a Generalized Additive Model (GAM) with a smooth function fitted by cubic splines. Hazard ratio estimates (solid line) along with their 95% confidence intervals (gray area) are plotted on a logarithmic scale.

Fig. 2. Kaplan-Meier survival curve by baseline NLR values.

Kaplan-Meier curve illustrates the overall survival of patients stratified by their Neutrophil-to-Lymphocyte Ratio (NLR) values. Patients with a higher NLR had a significantly lower overall survival compared to those with a lower NLR (p < 0.001); the rate of deaths was more than double in patients with higher NLR levels.

Fig. 3. Predicted Hazard Rate by NLR levels and number of CV risk factors.

The graph shows the predicted hazard rates for different combinations of the Neutrophil-to-Lymphocyte Ratio (NLR) and the number of cardiovascular (CV) risk factors adjusted for age and previous venous thrombosis. Patients with higher NLR ( ≥ 5) and more CV risk factors exhibit significantly higher predicted hazard rates, particularly as the number of CV risk factors increases.