Prediction of thrombosis in polycythemia vera: Development and validation of a multiple factor-based prognostic score system

BACKGROUND: Thrombosis is an important cause of death in patients with polycythemia vera (PV). The conventional stratification of thrombosis may ignore some potential risk factors. OBJECTIVES: This study aimed to develop and validate a multiple factor-based prediction model of thrombosis for the 2016 World Health Organization-dened PV. METHODS: Clinical and next-generation sequencing data from 2 cohorts of patients with PV were analyzed. Multivariable Cox regression analyses were conducted for the identification of thrombotic risk factors and model development. RESULTS: The study involved 372 patients in the training cohort and another 195 patients in the external validation cohort. Multivariable analyses indicated that age ≥60 years (hazard ratio [HR] 2.56, 95% CI 1.51-4.35, P < .001), cardiovascular risk factors (HR 4.22, 95% CI 2.00-8.92, P < .001), at least 1 high-risk mutation for thrombosis (mutations in DNMT3A, ASXL1, or BCOR/BCORL1) (HR 4.35, 95% CI 2.62-7.21, P < .001), and previous thrombosis (HR 5.93, 95% CI 3.29-10.68, P < .001) were independent risk factors of thrombosis. After assigning coefficient-weighted scores to each risk factor mentioned above, a multiple factor-based prognostic score system of thrombosis (MFPS-PV) was developed, classifying patients into low-risk, intermediate-risk, and high-risk groups. Patients in the 3 groups had notably different thrombosis-free survival rates (P < .001). The MFPS-PV outperformed the conventional model in discrimination power (C-statistic: 0.87 [95% CI 0.83-0.91] vs 0.80 [95% CI 0.74-0.86]). The MFPS-PV was well calibrated and remained consistent during external validation. CONCLUSION: The MFPS-PV, integrating genetic and clinical characteristics for the first time, shows excellent accuracy and utility for thrombosis prediction in WHO-defined PV.