AbstractAbstract 1743Essential thrombocythemia (ET) is a myeloproliferative Neoplasm (MPNs) marked by a risk of thrombotic and hemorrhagic complications, and by a long-term risk of evolution to myelofibrosis (MF), myelodys-plastic syndrome (MDS), and acute leukemia (AL). In addition to its role in pathophysiology and diagnosis, the constitutively active JAK2V617F mutation may be a prognostic marker because the percentage of circulating mutated alleles (%V617F) appears to be significantly higher in patients who develop vascular complications.Interferon alfa2a (pegasis) is a nonleukemogenic drug that can induce cytogenetic remissions or reversion from monoclonal to polyclonal patterns of hematopoiesis in some cases, this is the first study addressing the effects of pegasis in ET. Methods.Inclusion criteria were: Patients with ET diagnosed as per WHO classification 2008, age 18 to 45 years, and either no previous treatment or Hydroxyurea or anagralide for less than 1 years. ET diagnosis workup included ferritin, exclusion of secondary causes like infections and not meeting WHO criteria for PV, MDS and CML Pretreatment evaluation also included patient history, physical examination, complete blood count (CBC) and serum chemistries (UE), including liver and renal function studies, thyroid function tests (TFT), and molecular study for JAK2V617F mutation.Exclusion criteria included (significant hepatic and renal dysfunction, history of psychiatric disorder, in particular depression, autoimmune hepatitis, severe cardiac dysfunction, known hypersensitivity to IFN. The primary end point was hematologic response to pegasis at 12 months. Complete hematologic response (CR) as per ELN guidelines’ and Molecular response (MR) was defined as “complete” when JAK2V617F became undetectable with the technique used (ie, %V617F < 1%), “partial” when > 50% decrease of baseline %V617F was obtained, and “minor” when %V617F decrease was between 20% and 49%. Follow-up evaluations included adverse event (AE) assessment monthly for 3 months, then every third month until the 12th month with CBC, UE weekly during the first month and monthly thereafter. TFT, CBC, JAK2 mutation studies were taken every 6 months. After inclusion, HU was stopped 2 weeks before Pegasis initiation. Pegasis was started subcutaneously at 50 microgram weekly for 4 weeks then 135 microgramg/wk from week 5.Baseline characteristics of the patients are. Median age was 31.5 years (19–44) years), and 16 patients were males 24 were femals Five patients had a history of major thrombotic events. Treatment before inclusion included HU in 15 patients, and no treatment in the remaining 25 patients, all recently diagnosed.JAK2 mutation was found in all patientsAll the patients responded to Pegasis at the 12-month evaluation including 35 hematologic CRs (94.6%), and 5 PRs (5.4%). Cumulative incidences of hematologic CRs and PRs showing that 100% of responses were achieved within 12 months.No patient experienced signs or symptoms of thrombosis or hemorrhage during the whole study period. Median relative decrease of %V617F during the first year was 50% (33%-60%). %V617F decreased in all patients,After the first year, %V617F continued to decrease without evidence for a plateau, the proportion of mutant JAK2 being always similar or lower in the last sample compared with the previous one and none of the responding patient experienced an increase of %V617F during follow-up. Median %V617F was, 58% at 12 months, (P<.001). Complete or partial MR was observed in all patients.Hematologic response was achieved in all of the patients within 2 months and were sustained beyond the first year. Most common toxicities during the first month included musculoskeletal pain in 6 patients, skin toxicity in 4, and GI symptoms in 2, none of the toxicity exceeds WHO Grade 2. Conclusion.Pegylated Interferon alfa2a is effective and promising treatment for ET Reducing the vascular risk and preventing evolution to MF, MDS, and AL.with low toxicity profiles and good Hematological and Molecular response, Percentage of V617F appears to be a good tool to monitor minimal residual disease and to evaluate treatment efficacy however further studies are needed to confirm these results. Disclosures:Yassin:Qatar National Research Fund: Patents & Royalties, Research Funding. Off Label Use: use of pegelated interferon alfa 2a in treatment of patients with ET. Al-Dewik:Qatar National Research Fund: Patents & Royalties, Research Funding. Rafii El-Ayoubi:Qatar National Research Fund: Patents & Royalties, Research Funding.