Case-Based Discussion: Management Strategies for Hydroxyurea-Resistant Polycythemia Vera

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:

1. Hematocrit persistently >45% despite maximum tolerated hydroxyurea (2g daily)
2. WBC consistently >11,000/μL
3. Development of constitutional symptoms (fatigue, night sweats)

Second-line therapy options:

1. Ruxolitinib:
   1. FDA-approved for second-line setting
   2. Recommended starting dose: 10mg twice daily
   3. Excellent for symptom control and hematocrit management
   4. Growing evidence for molecular responses
2. Interferons (pegylated or ropeginterferon):
   1. Underutilized in community practice
   2. Potentially more appropriate for younger patients (long-term benefits)
   3. Requires several months to achieve optimal response
   4. Can be used in second-line setting per NCCN guidelines

Treatment goals:

1. Primary: Maintain hematocrit <45% consistently
2. Secondary: Control WBC count (<11,000/μL)
3. Tertiary: Normalize platelet count
4. 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.