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

- 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)

- Platelet count>400 x 10 to 9/L and WBC less than 2.5 x 10 to 9/L at any dose of
Hydroxyurea (for a period of at least 2 months). Platelet count>400 x 10 to 9/L and
Hb less than10 g/dl at any dose of Hydroxyurea (for a period of at least 2 months)
Progressive splenomegaly or hepatomegaly (>5cm or appearance of new splenomegaly or
hepatomegaly) in a patient being treated for splenomegaly In patients with baseline
splenomegaly an increase by > 5 cm over baseline

- Not achieving the desired reduction of HCT with the addition of Hydroxyurea in
patients who do not tolerate enough frequent venesections after 3 months of at least
2 g/day of Hydroxyurea (2.5 g/day in patients with a body weight>80 kg)

- Not achieving the desired stable reduction of WBC when leukocytes are a target of
therapy after 3 months of at least 2 g/day of Hydroxyurea (2.5 g/day in patients with
a body weight>80 kg)

- 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.

- 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)

- 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)

- No 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