Thrombosis free survival in 734 patients with essential thrombocythemia (WHO 2016)stratified according to the revised IPSET-thrombosis score : a report of the registro italiano Trombocitemie (RIT)

Background: The Revised International prognostic Score for Thrombosis in Essential Thrombocythemia (R-IPSET-Th) is based on different combinations of 3 parameters: Age >60 years (Age >60), JAK2 V617F mutation (JAK2+), and Prior Thrombosis (PrTh+). Aim: To validate the R-IPSET-Th in a cohort of ET patients reclassified according to the WHO 2016 criteria. Methods: The ET patients of the web-based Registro Italiano Trombocitemie (RIT) were stratified, according to the R-IPSET-Th score, in 4 thrombotic risk groups: Very Low Risk (VLR: No Age>60, No JAK2+, No PrTh+), Low risk (LR: only JAK2+), Intermediate Risk (IR: only Age>60), High Risk (HR: PrTh+ or Age>60 with JAK2+). The first thrombotic events occurring during the follow-up (ThFUP) were reported (n,%, n/100 pt-yr) for each group, together with thrombosis free survival (TFS, time from diagnosis to the first ThFUP). Results: Overall, 734 ET patients were analyzed (females 62%). Data at diagnosis were: Age>60 in 286 (39%), JAK2+ in 417 (57%), and PrTh+ in 126 (17%) patients. Moreover: cardiovascular risk factors (CVRF) in 53%, PLT >1000 x 109/L in 17%, and WBC >10 x 109/L in 25% of patients. The patients were: VLR 193 (26%), LR 197 (27%), IR 79 (11%), and HR 265 (36%). Their median FUP was 12, 12, 9, and 11 years, respectively. The rates of treatment were: 82%, 92%, 92%, 91% with anti-platelet (AntiPLT) drugs (mainly low dose aspirin); 67%, 61%, 94%, 95% with Cytoreductive drugs (mainly hydroxycarbamide, HC). The ThFUP (n 103, 14%) increased (p<0.001) with the risk score: in VLR (n 15, 8%), in LR (n 20, 10%), in IR (n 12, 15%), in HR (n 56, 21%). The ThFUP/100 pt-yr similarly increased (p<0.01) as follows: 0.60%, 0.79%, 1.61%, and 1.91%, respectively. The TFS progressively decreased (p<0.001) from VLR group to HR group (Figure 1). In detail, the probability of TFS in the 4 risk groups was at 5 years 0.98, 0.97, 0.94, 0.88 and at 20 years 0.85, 0.87, 0.78, 0.54, respectively. An high concordance index (Harrell C) was found (0.82). A comparative stratification according to the R-IPSET-Th score and other thrombotic risk scores (conventional, IPSET, IPSET-Th) was done. Conclusions: This study of the Registro Italiano Trombocitemie (RIT) documented that the Revised International Prognostic Score for Thrombosis in Essential Thrombocythemia (R-IPSET-Th) was able to stratify patients in 4 groups with increasing risk for thrombosis during the follow-up (p<0.001).