Inclusion Criteria:

- A diagnosis of Essential Thrombocythemia (ET) or Polycythemia Vera (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.

- Diagnosis < 3 years prior to 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

- 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 (0, 1 or 2 on scale 0 -4).

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
(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

Other Inclusion criteria (Both Strata)

- Diagnosed less than 3 years prior to entry on trial

- Never treated with cytoreductive drugs except hydroxyurea for up to 3
months maximum (phlebotomy, aspirin allowed)

- Age: > 18 years (no upper limit)

- Ability and willingness to comply with all study requirements

- Signed informed consent to participate in this study.

- Willing to participate in associated correlative science biomarker study

- Serum creatinine < 1.5 x upper limit of normal

- ST and ALT < 2 x upper limit of normal

- Total Bilirubin within normal limits

- No known PNH (paroxysmal nocturnal hemoglobinuria) clone

- No concurrent hormonal oral contraceptive use

Exclusion Criteria:

(ANY of the following, both strata)

- Known to meet the criteria for primary myelofibrosis (as opposed to ET) by
WHO 2008

- Any contraindications to pegylated interferon or hydroxyurea

- Presence of any life-threatening co-morbidity

- History of active substance or alcohol abuse within the last year

- Subjects who are pregnant, lactating or of reproductive potential and not
practicing an effective means of contraception

- History of psychiatric disorder (e.g. depression)

- History of autoimmune disorder (e.g. hepatitis)

- 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

- Splanchnic vein thrombosis (includes Budd-Chiari, portal vein, splenic and
mesenteric thrombosis)

- 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

- Neutrophil count <1.5 x 10 to 9/L

- JAK2 exon 12 mutation

- Patients cannot meet criteria for post PV or post ET-MF (see appendix B)

- 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.

- No previous exposure to any formulation of pegylated interferon

- 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 within normal limits