P010 | Next generation sequencing in triple negative essential thrombocythemia: impact of additional mutations in risk assessment

Introduction. Triple Negative Essential Thrombocythemia (TN ET) represents 10% of ET cases and is known for its indolent course, with limited thrombotic and disease progression risk. Next Generation Sequencing (NGS) analysis is not routinary applied in ET, despite prognostic significance of additional myeloid mutation has been explored in indolent myeloproliferative neoplasms and new molecular tools were introduced. Aim of the study was to analyze incidence and prognostic significance of additional mutations in TN ET.Methods We retrospectively analyzed 28 consecutive WHO-defined TN ET diagnosed between 1994 and 2024 at the Divisions of Hematology of Udine. Molecular status was defined as soon as analysis were available. NGS analysis was perform during chronic phase on peripheral blood samples. We used a 30 myeloid gene panel (TET2, ASXL1, DNMT3A, FLT3, NPM1, CEBPA, IDH1, IDH2, RUNX1, TP53, JAK2, MPL, CALR, KRAS, HRAS, NRAS, PTPN11, CBL, BRAF, SF3B1, SRSF2, U2AF1, ZRSR2, WT1, CSF3R, ETV6, EZH2, KIT, SETBP1, ABL1).Results. At diagnosis, median age was 49 years (range: 17-80), with a female prevalence (64%); median platelet count was 727,6 x109/L, while hemoglobin and leukocyte count were normal; 4 (14%) patients had symptoms, 2 (7%) had splenomegaly and 12 (43%) had ≥1 cardiovascular risk factor; 2 (7%) had arterial thrombosis. According to r-IPSET, 3 (10,7%) were at high risk, 8 (28,6%) at intermediate and 17 (60,7%) at very low. With a median follow up of 4 years (range: 1-30), 4 (14%) adverse events were noted in 4 patients (1 arterial thrombosis, 1 major bleeding, 1 leukemic progression, 1 death). In total, NGS revealed 16 mutations and 7 variants of uncertain significance in 14 (50%) patients. Among the former, the majority were DTA (DNMT3A, ASXL1, TET2; n=9) and non-canonical driver genes (JAK2, CALR, MPL; n=4) mutations. Overall 15-years OS and EFS were 84% and 64%. Patients with ≥3 additional mutations (n=3) had inferior 5-years OS (67% vs 100%, p=0.011) and EFS (67% vs 100%, p