Essential thrombocythemia(ET) is a chronic myeloproliferative neoplasm characterized by sustained thrombocytosis, bone marrow megakaryocytic hyperplasia and an increased risk of thrombosis and hemorrhage. The goal of treatment is to prevent the development of vascular complications without increasing the risk of transformation. Patients aged>60 years or a history of thrombosis have a high risk of thrombosis while those with a platelet count>1,500x109/l have a higher risk of hemorrhage.Patients with low-risk ET can be managed with low-dose of acetylsalicylic acid or even observation only, while patients with a high-risk disease are candidates to cytoreductive treatment, hydroxyurea being the first choice therapy. Anagrelide is the most suitable option for patients with resistance or intolerance to hydroxyurea. All patients must be submitted to a rigorous control of cardiovascular risk factors. 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 study addressing the safety efficacy and toxicity of pegasis( once weekly versus once monthly ) in ET MethodsInclusion 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 hematological response to pegasis at 12 months. Complete hematological 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 mcg/wk from week 5.all patients achieved complete hematological remission from week 10 were randomized into two arms arm(A)135 mcg/wk and arm(B) 135 mcg/monthBaseline characteristics of the patients are. Median age was 31.5 year vs 30 year, and 20 patients in each arm 18 patients were males 22 were females three patients had a history of major thrombotic events. Treatment before inclusion included HU in 18 patients, and no treatment in the remaining 22 patients,JAK2 mutation was found in all patients All the patients responded to Pegasis at the 12-month evaluation including 40 hematological CRs (100%)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 52% decreased in arm A versus 50 % in arm B,.Hematological 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 versus 2, skin toxicity in 4 versus 0, and GI symptoms in 2 versus 0 , none of the toxicity exceeds WHO Grade 2 with no stsatistical differences between the two groups. Conclusion135 mcg Pegasis once monthly is as effective as once weekly dose with reduced toxicity Reducing the vascular risk and preventing evolution to MF, MDS, 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 and to look for the efficacy of more reduced doses. Disclosures:Yassin:qatar national research fund: Patents & Royalties, Research Funding. Al-Dewik:qatar national research fund: Patents & Royalties, Research Funding. Cassinat:qatar national research fund: Patents & Royalties, Research Funding.