Thrombosis in Primary Myelofibrosis: Incidence and Risk Factors.

Abstract 2915

Poster Board II-891

Few epidemiologic studies have been conducted to evaluate at which extent vascular complications can influence the prognosis of patients with primary myelofibrosis (PMF). We assessed the cumulative rate and predictive factors of major cardiovascular vascular (CV) events in 707 patients (M/F 465/242, median age 62, range 11-90 years) with PMF from 4 European institutions. Patients were diagnosed during the period February 1973 - April 2008 and followed for a total of 2,909 patient-years (pt-yr) of observations (median, 2.92 years; 25th percentile, 1.14 years; 75th percentile, 5.92 years). A total of 236 deaths (33%) were recorded for an overall mortality of 7.7% pt-yr. Of them, only 12 well-documented deaths (2%, 0.39% pt-yr) were attributable to cardiovascular causes, whereas the majority of fatalities were due to non-CV events. Fatal and non-fatal thrombosis (myocardial infarction, stroke, peripheral arterial thrombosis, venous thromboembolisms (including splanchnic, cerebral and legs) was registered in 51 (7.2%) patients, with a rate of 1.75% pt-yr. If deaths from non-CV causes were considered as competing events, we estimated that the adjusted rate of major thrombotic events at 10 years would have been 2.2% pt-yr. In a multivariable model, age >60 yrs (HR 2.34, 95%CI 1.24-4.39, p=0.01) and JAK2 mutational status (HR 1.92, 95%CI 1.10-3.34, p=0.02) were significantly associated with thrombosis while the strength of the association between leukocyte count > 15 ×10⁹/L and CV events was of borderline significance (HR 1.72, 95%CI 0.97-2.72, P= 0.06). The highest incidence of fatal and non-fatal thrombosis was observed when the mutation was present along with leukocytosis (3.9% pt-yr, HR 3.13, CI 1.26-7.81). This study is the largest hitherto carried out in this setting and shows that the rate of major CV events in PMF is comparable to that reported in essential thrombocythemia and increases in aged patients as well as in those with the JAK2 V617F mutation and leukocytosis.