Thrombosis in myeloproliferative neoplasms: a viewpoint on its impact on myelofibrosis, mortality, and solid tumors

Abstract

This viewpoint summarizes findings from analyses of large personal patient databases of myeloproliferative neoplasms (MPNs) to assess the impact of thrombosis on mortality, disease progression, and second cancers (SC). Despite advances, the current incidence of arterial and venous thrombosis remains a challenge. These events appear to signal a more aggressive disease course, as evidenced by their association with myelofibrosis progression and mortality using multistate models and time-dependent multivariable analysis. Inflammatory biomarkers, such as the neutrophil-to-lymphocyte ratio (NLR), are associated with the aggressiveness of polycythemia vera (PV) and essential thrombocythemia (ET), linking thrombosis to SC risk. This suggests a common inflammatory pathway likely influencing cardiovascular disease and cancer incidence. Notably, this is observed more frequently in younger patients, likely due to prolonged exposure to MPN and environmental inflammatory triggers. These data underscore the need for new studies to validate these associations, delineate the sequence of events, and identify therapeutic targets to mitigate thrombotic events and potentially improve overall patient outcomes in MPN.

Fig. 1. Thrombosis affects survival and disease progression in prePMF, ET and PV.

A–C show the probability of progression to myelofibrosis -MF- (red lines) or to blast phase -BP- (blu lines) directly (solid lines) from the diagnosis of pre-PMF, ET and PV, respectively, or via thrombosis (dashed lines). Panels D, E and F show the probability of death directly (solid lines) from the diagnosis of pre-PMF, ET and PV, respectively, or via thrombosis (dashed lines).

Fig. 2. Neutrophil-to-lymphocyte ratio (NLR) and the risk of total thrombosis, MF evolution and death.

A Generalized additive proportional hazard models (GAM) for the prediction of total thrombosis, MF evolution and death according to Neutrophil-to-lymphocyte ratio (NLR): the effect of NLR is analyzed on a continuous scale by GAM smooth function with cubic splines. Hazard-ratio estimates (solid line) along with their 95% confidence intervals (gray areas) are plotted in logarithmic scale. B Multivariable Cox proportional hazards regression model with fixed and time-dependent variables showing the significant independent effect of NLR on the risk of death.

Fig. 3. Arterial thrombosis is a risk factor of second cancer in MPNs.

Odds Ratios (ORs) of second cancer obtained from a multivariable conditional regression model stratified for age at MPN diagnosis: red triangles represent OR of second cancer for MPN patients with age < 60 years; blue circles represent the OR of second cancer for MPN patients with age ≥ 60 years. Solid lines represent the corresponding 95% Confidence Intervals (CIs).