Case-Based Discussion: Management Strategies for Hydroxyurea-Resistant Polycythemia Vera
Panelists discuss how managing advanced polycythemia vera requires tailored approaches beyond hydroxyurea when patients show resistance (persistent hematocrit >45%, elevated white blood cell counts, ongoing symptoms), with experts advocating for either second-line ruxolitinib for rapid symptom and hematologic control or interferons (particularly in younger patients), while emphasizing the importance of addressing modifiable cardiovascular risk factors like smoking cessation.
Summary of Advanced Polycythemia Vera Case Management
Case Presentation
- 67-year-old man with high-risk polycythemia vera (PV), advanced disease
- Presenting symptoms: Frequent headaches, dizziness
- Risk factors: Active smoker, age >60
- Initial labs (February 2018):
- Hemoglobin 20.5 g/dL
- White blood cell count (WBC) 13,000/μL
- Platelets 380,000/μL
- JAK2 V617F mutation (65% VAF)
- Bone marrow findings consistent with PV
- Initial treatment:
- Aspirin
- Hydroxyurea (escalated to 2g daily)
- Phlebotomy
- Clinical course (February 2019):
- Continued need for phlebotomies (2 in previous 3 months)
- New symptoms: fatigue and night sweats
- Hematocrit remained elevated at 47%
- WBC persistently elevated at 13,000/μL
- Meets criteria for hydroxyurea resistance
Management Considerations
Treatment failure defined by:
- Hematocrit persistently >45% despite maximum tolerated hydroxyurea (2g daily)
- WBC consistently >11,000/μL
- Development of constitutional symptoms (fatigue, night sweats)
Second-line therapy options:
- Ruxolitinib:
- FDA-approved for second-line setting
- Recommended starting dose: 10mg twice daily
- Excellent for symptom control and hematocrit management
- Growing evidence for molecular responses
- Interferons (pegylated or ropeginterferon):
- Underutilized in community practice
- Potentially more appropriate for younger patients (long-term benefits)
- Requires several months to achieve optimal response
- Can be used in second-line setting per NCCN guidelines
Treatment goals:
- Primary: Maintain hematocrit <45% consistently
- Secondary: Control WBC count (<11,000/μL)
- Tertiary: Normalize platelet count
- Symptom management
Additional interventions:
- Smoking cessation is critical to reduce thrombotic risk
- Comprehensive cardiovascular risk factor management
The panel emphasized the importance of: 1) recognizing hydroxyurea resistance promptly, 2) consistent hematocrit control below 45%, 3) WBC control, and 4) addressing modifiable cardiovascular risk factors like smoking as part of holistic PV management.
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