What are the initial treatment recommendations for patients with myeloproliferative diseases (MPD)?

Initial Treatment Recommendations for Myeloproliferative Diseases (MPD)

The initial treatment for myeloproliferative diseases should be risk-stratified, with low-risk patients receiving aspirin and phlebotomy (for PV), while high-risk patients should receive cytoreductive therapy in addition to these measures. 1

Risk Stratification

Risk stratification is essential for determining appropriate treatment:

• High-risk patients include: 1

  • Age ≥60 years
  • History of prior thrombosis
  • Platelet count >1,500 × 10^9/L (increased bleeding risk)

• Low-risk patients include: 1

  • Age <60 years
  • No history of thrombosis

Treatment Recommendations by Disease Type

Polycythemia Vera (PV)

Low-Risk PV:

• Phlebotomy to maintain hematocrit <45% 1
  • Target may be individualized (e.g., 42% for women)
• Low-dose aspirin (81-100 mg/day) 1
• Monitor for indications to initiate cytoreductive therapy every 3-6 months 1

High-Risk PV:

• Phlebotomy to maintain hematocrit <45% 1
• Low-dose aspirin (81-100 mg/day) 1
• Cytoreductive therapy with hydroxyurea as first-line option 1
  • Alternative options for younger patients or pregnant patients: interferon alfa-2b, peginterferon alfa-2a, or peginterferon alfa-2b 1

Essential Thrombocythemia (ET)

Very Low-Risk, Low-Risk, or Intermediate-Risk ET:

• Observation is appropriate for very low-risk or low-risk ET 1
• Low-dose aspirin (81-100 mg/day) can be considered 1
  • Use with caution in patients with acquired von Willebrand disease due to increased bleeding risk 1, 2

High-Risk ET:

• Low-dose aspirin (81-100 mg/day) 1
• Cytoreductive therapy with hydroxyurea as first-line option 1, 3
  • Target platelet count <400 × 10^9/L 3
  • Target WBC count <10 × 10^9/L 3

Cytoreductive Therapy Options

Hydroxyurea

• First-line cytoreductive agent for high-risk PV and ET 1, 3
• Dosing: Start with 15-20 mg/kg/day, titrate to achieve target counts 3
• Monitor for resistance or intolerance 1
• Use with caution in younger patients (<40 years) due to potential leukemogenic risk 1

Interferon Alpha

• Consider for younger patients or pregnant patients requiring cytoreductive therapy 1
• Can induce molecular responses (reduction in JAK2V617F allele burden) 1

Ruxolitinib

• FDA-approved for PV patients with inadequate response to or intolerance of hydroxyurea 1, 4
• Effectively reduces JAK2V617F gene expression, myelofibrosis, and symptoms 4

Monitoring Response

• Evaluate every 3-6 months for: 1

  • New thrombosis or bleeding
  • Disease-related symptoms using MPN Symptom Assessment Form
  • Need for frequent phlebotomy
  • Progressive splenomegaly
  • Progressive leukocytosis
  • Symptomatic thrombocytosis

• Target response includes: 3

  • Platelet count <400 × 10^9/L
  • WBC count <10 × 10^9/L
  • Hematocrit <45% (for PV)
  • Resolution of disease-related symptoms

Special Considerations

• Thrombosis risk management: Aggressively manage cardiovascular risk factors in all patients 1, 5

• Bleeding risk: Monitor for acquired von Willebrand disease in patients with extreme thrombocytosis 1, 2

• Aspirin dosing: Some patients may benefit from twice-daily aspirin regimen, particularly those with inadequate platelet inhibition 6

• Thalidomide/Lenalidomide therapy: When these agents are used in multiple myeloma, prophylactic low-dose aspirin is effective for preventing thromboembolism 7

• Resistance to hydroxyurea: Consider alternative agents (interferon alpha for PV, anagrelide for ET, or ruxolitinib for PV) 1, 3