What is the treatment for polycythemia vera?

Treatment of Polycythemia Vera

The cornerstone of polycythemia vera treatment is phlebotomy to maintain hematocrit <45% and low-dose aspirin (81-100 mg daily), with cytoreductive therapy (hydroxyurea or interferon-α) added for high-risk patients (age ≥60 years or history of thrombosis). 1

Risk Stratification

Risk stratification is essential for determining appropriate treatment:

Risk Category	Risk Factors
Low Risk	Age <60 years and no history of thrombosis
High Risk	Age ≥60 years or history of thrombosis

Treatment Algorithm

For All Patients:

• Phlebotomy: Target hematocrit <45% (shown to significantly reduce thrombotic events) 2, 1
  • Initial regimen: 300-450 ml blood extraction weekly or twice weekly until target achieved
  • Maintenance: Frequency adjusted based on hematocrit levels
• Low-dose aspirin: 81-100 mg daily (if no contraindications) 2, 1
  • Significantly reduces cardiovascular death, non-fatal MI, stroke, and venous thromboembolism
  • Use with caution in patients with extreme thrombocytosis (≥1000 × 10^9/L) due to risk of acquired von Willebrand disease 3

Additional Treatment for High-Risk Patients:

• Cytoreductive therapy is indicated for:
  • Age ≥60 years
  • History of thrombosis
  • Progressive splenomegaly
  • Intolerance to phlebotomy
  • Poor hematocrit control 2, 1

First-line Cytoreductive Options:

1. Hydroxyurea 2, 1

   • Well-established efficacy and generally well-tolerated
   • Caution: Potential risk of leukemogenesis with long-term use (though evidence is inconclusive)
   • Consider alternative treatments in young patients or those previously treated with myelosuppressive agents

2. Interferon-α 2, 1

   • Particularly suitable for:
     • Younger patients
     • Women of childbearing age
     • Patients with intractable pruritus
   • Can induce high rates of hematological response and reduce JAK2V617F mutant allele burden
   • Newer pegylated forms have improved tolerability

Second-line Options:

• Ruxolitinib (JAK1/2 inhibitor) 4, 5

  • For patients intolerant or resistant to hydroxyurea
  • Effective for hematocrit control, reducing spleen size, and improving PV-related symptoms, especially pruritus

• Busulfan 6, 5

  • Reserved for elderly patients with limited life expectancy who are intolerant to other therapies

Monitoring and Follow-up

• Complete blood count every 3-6 months
• Regular assessment of symptoms and complications
• Aggressive management of cardiovascular risk factors
• Iron supplementation only for severe symptomatic iron deficiency

Treatment Efficacy and Outcomes

• With proper management, median survival is approximately 14-27 years 3
• Younger patients (age ≤40) may have survival of 35-37 years 6
• Phlebotomy alone in low-risk patients is associated with a thrombosis rate of 0.8% per year 7
• Risk of disease progression:
  • Myelofibrosis: 7-12.7% at 10 years 3, 6, 7
  • Acute myeloid leukemia: 1-6.8% 3, 6, 7

Common Pitfalls and Caveats

1. Inadequate hematocrit control: Only 32-44% of patients maintain hematocrit <45% with phlebotomy alone 7. Regular monitoring is essential.

2. Overuse of cytoreductive therapy: Not all patients require cytoreductive therapy. Reserve for high-risk patients or those with poor control on phlebotomy.

3. Ignoring symptoms: Beyond thrombosis prevention, symptom management (pruritus, erythromelalgia, splenomegaly) is important for quality of life.

4. Neglecting cardiovascular risk factors: Aggressive management of modifiable risk factors (smoking, hypertension, diabetes) is crucial.

5. Iron supplementation caution: Avoid routine iron supplementation as it can increase erythropoiesis; reserve for symptomatic deficiency only.