Pegylated Interferon Alfa-2a Salvage Therapy in High Risk Polycythemia Vera (PV) or Essential Thrombocythemia (ET)

Inclusion Criteria: A diagnosis of ET or PV shall be made in accordance with the WHO (2008) criteria (Swerdlow 2008) as shown below (Values below are at the time of diagnosis, not study entry): * Polycythemia Vera (2 major criteria required) 1. Hb \>18.5g/dl (♂) or 16.5g/dl (♀) or HCT \>99 percentile reference range or Elevated red cell mass (\>25% above mean predicted value) or Hb \>17g/dl (♂) or 15g/dl (♀) if associated with a sustained rise from baseline with no apparent cause (e.g. treated iron deficiency). 2. Presence of JAK2V617F * If source documentation of diagnostic criterion #1 cannot be obtained, then diagnosis can be made with (1) the addition of an erythropoietin level below the reference range of normal AND (2) bone marrow biopsy showing hypercellularity for age with trilineage (panmyelosis) with prominent erythroid, granulocytic, and megakaryocytic proliferation. * Essential Thrombocythemia (all 6 criteria required) 1. Platelets count ≥ 450 x 10 to 9/L 2. Megakaryocyte proliferation with large and mature morphology. No or little granulocyte or erythroid proliferation. Patients may have up to and including 2+ marrow reticulin fibrosis. 3. Not meeting WHO criteria for CML, PV, MDS, PMF or over myeloid neoplasm 4. Demonstration of clonal cytogenetic marker or no evidence for a reactive thrombocytosis. 5. Absence of a leukoerythroblastic blood picture. 6. May participate in study without presence of JAK2V617F. * Patients must have high risk disease as defined below: High risk PV ANY ONE of the following: * Age ≥ 60 years * Previous documented thrombosis, erythromelalgia or migraine (severe, recurrent, requiring medications, and felt to be secondary to the MPN) either after diagnosis or within 10 years before diagnosis and considered to be disease related * Significant (i.e. ≥ 5cm below costal margin on palpation) or symptomatic splenomegaly (splenic infarcts or requiring analgesia) * Platelets ≥ 1000 x 10 to 9/L * Diabetes or hypertension requiring pharmacological therapy for ≥ 6 months High risk ET ANY ONE of the following: * Age ≥ 60 years * Platelet count ≥ 1500 x 10 to 9/L * Previous documented thrombosis, erythromelalgia or migraine (severe, recurrent, requiring medications, and felt to be secondary to the MPN) either after diagnosis or within 10 years before diagnosis and considered to be disease related * Previous hemorrhage related to ET * Diabetes or hypertension requiring pharmacological therapy for ≥ 6 months In addition patients must EITHER be intolerant or resistant to Hydroxyurea according to established criteria as follows: Any ONE of the following: * Platelet count ≥ 600 x 10 to 9/L after 3 months of at least 2 g/day of Hydroxyurea (2.5 g/day in patients with a body weight\>80 kg) * WBC \< 2.5 x 109/L or Hgb \< 11g/dl at any dose of hydroxyurea not to exceed 2g/day. * Progressive splenomegaly or hepatomegaly (\> 5cm from initiation of hydroxyurea) or the appearance of new splenomegaly or hepatomegaly while on MTD of hydroxyurea. * Not achieving a Hct \< 45% in order to eliminate the need for supplemental phlebotomies after 3 months of at least 2g/day or MTD of hydroxyurea. * Not achieving a WBC of \< 10 x 109/L after 3 months of at least 2g/day or MTD of hydroxyurea. * Having a platelet count \< 100 x 109/L on hydroxyurea at any dose without eliminating the need for supplemental phlebotomy or having progressive splenomegaly as defined above. * Development of a major thrombotic episode (CVA, myocardial infarction, severe migraines requiring medication, abdominal vein thrombosis, deep vein thrombosis) while being treated with maximal tolerated doses of hydroxyurea. * Presence of leg ulcers or other unacceptable Hydroxyurea-related non-hematological toxicities, such as unacceptable mucocutaneous manifestations, gastrointestinal symptoms, pneumonitis or fever at any dose of Hydroxyurea. OR have Splanchnic Vein Thrombosis (SVT) (includes Budd-Chiari, abdominal vein thrombosis, portal vein thrombosis, splenic vein thrombosis). For these patients the following additional inclusion/exclusion criteria apply: * \> 3 months since onset of SVT * SVT treated with oral anticoagulants but no aspirin * Liver enzymes not \> 2 times the normal value * Absence of encephalopathy, refractory or infected ascites, esophageal varicose of grade \> 1 at time of trial entry * Bone marrow biopsy confirmed diagnosis of PV or ET * JAK2-V617F mutations present * These patients may have a normal blood count at trial entry * Age over 18 years (no upper age limit) * Able and willing to comply with study criteria * Signed and informed consent to participant in this study * Willing to participate in associated correlative science biomarker study * Serum creatinine \< 1.5 x upper limit of normal * AST and ALT \< 2 x upper limit of normal * Total bilirubin within normal limits Exclusion Criteria: * Patients cannot have any other form of chemotherapy for their MPD (other than hydroxyurea). Specifically prior interferon or JAK2 inhibitors are prohibited. * If a patient has received prior hydroxyurea, they should be tapered off hydroxyurea over a period of the first 2 months of Pegylated interferon alfa-2a therapy. Taper is at the treating physician's discretion, but must be absent (completed) by the start of the third month. * Patients with a prior malignancy within the last 5 years (except for basal or squamous cell carcinoma, or in situ cancer of the cervix) * Presence of any life-threatening co-morbidity * History of active substance or alcohol abuse within the last year * Any contraindications to pegylated or non-pegylated interferon * Subjects who have a positive pregnancy test, are pregnant, lactating or of reproductive potential and not practicing an effective means of contraception * History of psychiatric disorder (e.g. depression; suicidal ideation; psychosis) Subjects with a history of mild depression may be considered for entry into this study, provided that a pretreatment assessment of the subject's affective status supports that the subject is clinically stable based on the investigator's normal practice for such subject. * History of autoimmune disorder (e.g. hepatitis; ITP; scleroderma; severe psoriasis affecting \> 10% of the body, rheumatoid arthritis requiring more than intermittent NSAID for management) * Hypersensitivity to IFN-α * HBV or untreated systemic infection * Known HIV disease * Evidence of severe retinopathy (e.g. CMV retinitis, macular degeneration) or clinically relevant ophthalmological disorder (e.g. due to diabetes mellitus or hypertension) * History or other evidence of decompensated liver disease * History or other evidence of chronic pulmonary disease associated with functional limitation * Thyroid dysfunction not adequately controlled * Any investigational drug \<6 weeks prior to the first dose of study drug or not recovered from effects of prior investigational agent. * Presence of JAK2 exon 12 mutation * Patients should not meet criteria for post PV or post ET-MF (see appendix B) * Previous exposure to any formulation of interferon * Subjects with any other medical condition, which in the opinion of the investigator would compromise the results of the study by deleterious effects of treatment. * History of major organ transplantation * History of uncontrolled severe seizure disorder * Inability to give informed written consent * Serum creatinine \> 1.5 x upper limit of normal * AST and ALT \> 2 x upper limit of normal * Total bilirubin \> 1.5 mg/ml * No detectable PNH (paroxysmal nocturnal hemoglobinuria) clone where tested * Concurrent hormonal contraceptive use