What is the treatment for polycythemia vera?

Treatment for Polycythemia Vera

The cornerstone of polycythemia vera (PV) treatment consists of phlebotomy to maintain hematocrit strictly below 45% and low-dose aspirin (100mg daily) for all patients, with cytoreductive therapy added for high-risk patients (age >60 years and/or history of thrombosis). 1

Risk Stratification

• PV patients are classified into two risk categories 1, 2:
  • High risk: Age >60 years and/or history of thrombosis
  • Low risk: Absence of both risk factors

First-Line Treatment for All PV Patients

• Phlebotomy therapy:

  • Target hematocrit strictly <45% in men (consider lower targets of 42% in women and African Americans) 3, 1
  • This target is supported by the CYTO-PV randomized clinical trial showing significantly reduced thrombotic events with strict hematocrit control 3
  • Phlebotomy should be performed with careful monitoring and appropriate fluid replacement to avoid hypotension or fluid overload 3

• Low-dose aspirin (100mg daily):

  • Recommended for all patients without contraindications 3, 1
  • Significantly reduces cardiovascular events as demonstrated in the European Collaboration on Low-dose Aspirin in Polycythaemia Vera (ECLAP) study 3
  • Use with caution in patients with extreme thrombocytosis (≥1,000 × 10^9/L) due to increased bleeding risk 4, 5

Cytoreductive Therapy Indications

Cytoreductive therapy should be added for:

• High-risk patients (age >60 years and/or history of thrombosis) 3, 1, 2
• Additional indications include 1:
  • Poor tolerance of phlebotomy or frequent phlebotomy requirement (>5 phlebotomies/year) 6
  • Symptomatic or progressive splenomegaly
  • Severe disease-related symptoms
  • Platelet counts >1,500 × 10^9/L
  • Progressive leukocytosis

Cytoreductive Agent Selection

• Hydroxyurea:

  • First-line cytoreductive agent for older patients (>40 years) 3, 1
  • Starting dose: 500mg twice daily 1
  • Resistance or intolerance is defined as 1:
    • Need for phlebotomy to maintain hematocrit <45% after 3 months of ≥2g/day
    • Uncontrolled myeloproliferation
    • Failure to reduce splenomegaly or related symptoms
    • Cytopenia or unacceptable side effects at any dose

• Interferon-α:

  • Preferred for younger patients (<40 years) and women of childbearing age 3, 1
  • Starting dose: 3 million U subcutaneously 3 times weekly 1
  • Has been shown to induce high rates of hematological response and significantly reduce the JAK2V617F mutant allele burden 3

• Ruxolitinib (JAK1/2 inhibitor):

  • Second-line option for patients resistant to or intolerant of hydroxyurea 7, 5
  • Particularly effective for alleviating pruritus and decreasing splenomegaly 5

Monitoring and Long-term Considerations

• Regular monitoring of blood counts and symptoms is essential 1
• Untreated PV has a significantly shortened survival (historically <2 years without treatment) 3, 4
• With modern treatment, median survival is approximately 14-15 years 5, 2
• Long-term complications to monitor for include:
  • Thrombotic events (incidence rate of 0.8% per year with phlebotomy alone) 6
  • Progression to myelofibrosis (7% at 10 years, 20% at 20 years) 6
  • Transformation to acute myeloid leukemia (approximately 3% at 10 years) 2

Special Considerations

• Arterial hypertension increases the risk of arterial thrombosis 6
• Higher JAK2V617F allele burden may increase risk of venous thrombosis 6
• Aggressive management of vascular risk factors (smoking, hypertension, etc.) is essential 3

Treatment Algorithm

1. All PV patients: Phlebotomy to hematocrit <45% + low-dose aspirin (100mg daily) 3, 1
2. If high-risk OR poor phlebotomy response OR significant symptoms: Add cytoreductive therapy 1
   • Age >40 years: Hydroxyurea (first-line) 1
   • Age <40 years or women of childbearing age: Interferon-α (first-line) 3, 1
   • If resistant/intolerant to first-line: Switch to alternative first-line agent or consider ruxolitinib 7, 5