How Epidemiology of Polycythemia Vera Has Changed in the Last 10 Years: Results From the Whole Prospective Cohort of Patients in Cyto-PV Trial As Compared with Eclap Prospective Cohort

Polycythemia vera (PV) is a chronic myeloproliferative neoplasms characterized by erythrocytosis, vasomotor disturbances, pruritus, risk of disease progression into acute myeloid leukemia or myelofibrosis and cardiovascular events, the last representing the main cause of morbidity and mortality. Since 2005 the V617F point mutation in Janus Kinase 2 (JAK2) gene gained a dominant role in determining the molecular basis and the diagnosis of PV. We compared the clinical epidemiology of the 1638 patients included in the ECLAP trial in the years 1997 to 2001, with that of a “modern” cohort of 365 PV, JAK2-positive patients included in the Italian CYTO-PV randomized clinical trial and followed from the year 2008 to 2012.

Patients were eligible in CYTO-PV trial and in ECLAP study if they met WHO-2008 diagnostic criteria and the criteria established by the PVSG or Pearson/Messinezy respectively. Clinical characteristics have been compared. The incidence of major cardiovascular events (CV death plus major thrombosis [stroke, acute coronary syndrome, transient ischemic cerebral attack, peripheral arterial thrombosis, pulmonary embolism, abdominal thrombosis, deep vein thrombosis) and total CV events incidence has been evaluated. The median follow up was 31.0 months (range 0– 48.13 months) and 33.1 months (range 0–63.6) for patients included CYTO-PV and in ECLAP respectively.

In CYTO-PV 49.3% patients with recent PV diagnosis were included (within 2 years prior inclusion) while in ECLAP the proportion was 35.5%. Mean age at recruitment was similar for patients in CYTO-PV (64.5 yrs) and ECLAP (65.4 yrs). History of thrombosis was reported in 28.9 % vs 38.6% patients in the CYTO-PV and in ECLAP, respectively (p<0.05). Consistently higher proportions of arterial and venous thrombotic events were found in ECLAP as compared to CYTO-PV. History of major bleeding was reported in 1.7% vs 4.8% of the patients in CYTO and ECLAP, respectively. Medical treatment at recruitment was more intensive in CYTO-PV vs. ECLAP: phlebotomy 72.3% vs 63.5% (ns), hydroxyurea (HU) 54.2 vs 48.4, antiplatelet drugs 84.9% vs 58.3% (p<0.05), aspirin 77.0% vs 50.2% (p<0.05), anti-hypertensive and hypocholesterolemic medications were administered respectively in 48.5% and 13% of CYTO–PV patients vs. 39% and 3.5% of ECLAP population (p<0.05) As compared with ECLAP, the incidence of risk of major thombosis in CYTO-PV was 2.7 vs 4.4 and of total CV events was 3.4 vs 5.5 per 100 person/years, respectively. The incidence of total CV events in CYTO-PV for the subgroups of patients with age <65 and no previous thrombosis (PT), age > 65 and no PT, age <65 and PT, age > 65 and PT at randomization was 2.2, 4.8, 3.5 and 3.4 per 100 person/years, respectively.

The comparison of these two cohorts of PV patients followed 10 years apart suggests that JAK-2 PV patients are currently better managed for the control of classical CV risk factors, are more frequently administered aspirin, and HU with better control of their disease, and eventually have a risk of thrombosis approximately half than in the past.

No relevant conflicts of interest to declare.