Phenotypes of JAK2-Mutated Polycythemia Vera and Essential Thrombocythemia with and without Thromboembolic Events: Results of the Hinc-207 (OSHO #91) Study

Thrombosis is the major cause of morbidity and mortality in polycythemia vera (PV) and essential thrombocythemia (ET). Age ≥60 years (y) and/or history of thrombosis labels patients (pts) as high-risk for thrombosis. Yet, thrombosis frequently occurs prior to the diagnosis of PV/ET. In a multicenter study of the East German Study Group (HINC-207; OSHO #091), the interaction between age and time occurrence of the first thrombosis as risk factors for thrombosis after diagnosis was studied. Methods After IRB approvals, JAK2 mutated adults with PV or ET were prospectively enrolled in 9 centers and centrally stratified in a one to two ratio (group A: pts with a history of thrombosis; group B: pts without thrombosis) with a pre-planned minimum of 60:120 pts. Based on a longitudinal and cross-sectional design, clinical and laboratory data at diagnosis, last follow-up, and thrombosis (for group A) were collected. Thrombosis prior to diagnosis was labeled as A1 and thrombosis after diagnosis as A2. Thrombosis risk factors were grouped into age-, previous thrombosis-, thrombosis prior to PV/ET-, cardiovascular (CV)-, thrombophilia-, and disease- (JAK2 allele burden, Hct, and WBC) related. Additionally, therapies [aspirin (ASS), anticoagulation, phlebotomy, and cytoreduction] and data from a study-own patient questionnaire were included. All pts signed informed consent. The primary endpoint was the phenotypic diversity in JAK2-mutated ET and PV pts with or without thrombosis. Results From April to Dec, 2019, 246 pts were recruited. Data on 237 pts (median age 62y; 59% females, 58% PV) are available. At diagnosis, pts in group A (n=71, median age 59.5y) tended to be younger than those in group B (n=166, median age 63y) (p=0.07). Yet, 70.4% thrombotic events (venous: median age 46.5y; arterial: median age 57y) occurred in A1 and correlated with younger age (p=0.03). Only 3 pts developed a second event after diagnosis. These were counted in A2 (n=24, median age at thrombosis: 61y). Overall, thrombosis occurred either prior to or within the first 3y after diagnosis in 63/71 (89%) pts. Age>60y could not be identified as a risk factor for thrombosis or type of thrombosis at any time point. The 5 y probability of no thrombotic event after diagnosis in pts >60y was 90.4% vs. 89.2% for pts 3y after diagnosis in pts >60y was 3.7% vs. 4.9% for pts