Treatment of Polycythemia Vera
The cornerstone treatment for polycythemia vera includes phlebotomy to maintain hematocrit strictly below 45% combined with low-dose aspirin (81-100mg daily) for all patients, with cytoreductive therapy added for high-risk patients (age >60 years and/or history of thrombosis). 1, 2
Risk Stratification
- High-risk patients are defined as those with age ≥60 years and/or prior history of thrombosis 2
- Low-risk patients are those <60 years with no history of thrombosis 2
- Additional factors that may influence risk assessment include cardiovascular risk factors and extreme thrombocytosis (platelet count >1500 × 10^9/L) 2
First-Line Treatment for All Patients
Phlebotomy
- Target hematocrit should be strictly maintained below 45% in men (with corresponding values for women) 2, 1
- This target is based on the CYTO-PV study which demonstrated that maintaining hematocrit <45% significantly reduced cardiovascular death and major thrombosis compared to a target of 45-50% 3
- Adequate hematocrit control (<45%) is achieved in only 32-44% of patients on phlebotomy alone, highlighting the need for careful monitoring 4
Antiplatelet Therapy
- Low-dose aspirin (81-100mg daily) is recommended for all patients without contraindications 2, 1
- The European Collaboration on Low-dose Aspirin in Polycythemia Vera (ECLAP) study demonstrated significant reduction in cardiovascular events with aspirin 2
Indications for Cytoreductive Therapy
Cytoreductive therapy should be added for patients with:
- High-risk status (age >60 years and/or history of thrombosis) 2, 1
- Poor tolerance of phlebotomy or frequent phlebotomy requirement (≥3 phlebotomies per year while on hydroxyurea indicates higher thrombotic risk) 2, 5
- Symptomatic or progressive splenomegaly 2
- Progressive leukocytosis 2
- Symptomatic thrombocytosis or platelet count >1500 × 10^9/L 2
- Progressive disease-related symptoms (pruritus, night sweats, fatigue) 2, 1
Selection of Cytoreductive Agents
Hydroxyurea
- First-line cytoreductive agent for older patients (>40 years) 2
- Initial dosage: 500mg twice daily, adjusted to maintain target blood counts 2
- Advantages: well-established efficacy, good tolerability in most patients 2
- Potential adverse effects: anemia, neutropenia, oral and skin ulcers, hyperpigmentation, nail changes 2
- Long-term leukemogenic risk remains controversial but appears lower than with other agents like pipobroman 2
Interferon-α
- Preferred for younger patients (<40 years) and women of childbearing age 2, 1
- Initial dosage: 3 million units subcutaneously 3 times weekly 2
- Advantages: not leukemogenic, can reduce JAK2V617F allele burden 1, 6
- Disadvantages: flu-like symptoms, fatigue, depression, higher cost 2, 7
- Pegylated forms may improve tolerability 2
Monitoring Response and Treatment Adjustment
- Monitor hematocrit, complete blood count, and symptoms every 3-6 months 2
- Bone marrow examination should be performed to rule out progression to myelofibrosis before initiating cytoreductive therapy 2
- Inadequate response to hydroxyurea is defined by:
Disease Progression and Complications
- With current treatment approaches, approximately 10% of patients transform to myelofibrosis and 5% to acute leukemia in the first decade of disease 2, 6
- The risk increases progressively beyond the first decade 2
- Annual incidence of thrombosis under phlebotomy alone is approximately 0.8% per year 4
- Patients requiring ≥3 phlebotomies per year while on hydroxyurea have a significantly higher thrombosis rate (20.5% vs 5.3% at 3 years) 5
Special Considerations
- For elderly patients with limited life expectancy (<10 years) and compliance issues, radioactive phosphorus (32P) at 2.3 mCi/m² every 3-4 months may be considered 2
- Ruxolitinib (JAK inhibitor) can be considered for patients with intolerance or resistance to hydroxyurea, particularly for alleviating pruritus and decreasing splenomegaly 6
- Aggressive management of cardiovascular risk factors is essential 2