What is the initial treatment approach for patients with myeloproliferative (myeloproliferative neoplasms) disorders?

Initial Treatment Approach for Myeloproliferative Neoplasms (MPNs)

The initial treatment for myeloproliferative neoplasms should be based on risk stratification, with low-risk patients receiving aspirin and phlebotomy (for PV), while high-risk patients should receive cytoreductive therapy with hydroxyurea as first-line treatment in addition to aspirin and phlebotomy. 1

Risk Stratification

Risk stratification is essential for determining the appropriate initial treatment approach:

• High-risk patients include those with:

  • Age ≥60 years 1
  • History of prior thrombosis 1
  • Extreme thrombocytosis (>1,500 × 10^9/L) 2

• Low-risk patients include those with:

  • Age <60 years 1
  • No history of thrombosis 1

Disease-Specific Treatment Approaches

Polycythemia Vera (PV)

• Low-risk PV patients:

  • Phlebotomy to maintain hematocrit <45% 1, 2
  • Low-dose aspirin (81-100 mg/day) 1, 2

• High-risk PV patients:

  • Phlebotomy to maintain hematocrit <45% 2, 1
  • Low-dose aspirin (81-100 mg/day) 2, 1
  • Cytoreductive therapy with hydroxyurea as first-line option 2, 1

Essential Thrombocythemia (ET)

• Low-risk ET patients:

  • Observation or low-dose aspirin if microvascular disturbances are present 2, 1

• High-risk ET patients:

  • Low-dose aspirin (81-100 mg/day) 2, 1
  • Cytoreductive therapy with hydroxyurea as first-line option 2, 1
  • Target platelet count <400 × 10^9/L 3

Primary Myelofibrosis (PMF)

• Treatment is based on prognostic scoring systems (IPSS, DIPSS, or DIPSS-plus) 2
• Risk categories determine treatment approach:
  • Low-risk: Observation or symptom-directed therapy 2
  • Intermediate to high-risk: Consider JAK inhibitors for symptomatic disease 4
  • High-risk: Consider allogeneic stem cell transplantation in eligible patients 2

Cytoreductive Therapy

• Hydroxyurea is the first-line cytoreductive agent for high-risk PV and ET 2, 1, 3

  • Titrate to achieve target platelet count <400 × 10^9/L 3
  • Target WBC count <10 × 10^9/L 3
  • Target hematocrit <45% (for PV) 3

• Interferon alpha should be considered for:

  • Younger patients (<40 years) 2, 5
  • Pregnant patients requiring cytoreductive therapy 1, 5
  • Patients intolerant or resistant to hydroxyurea 2

Monitoring Response

• Evaluate patients every 3-6 months for 1:

  • New thrombosis or bleeding
  • Disease-related symptoms
  • Need for frequent phlebotomy
  • Progressive splenomegaly
  • Progressive leukocytosis

• Response criteria include 2, 3:

  • Normalization of blood counts
  • Resolution of disease-related symptoms
  • No routine bone marrow monitoring needed for clinical follow-up

Special Considerations and Cautions

• Cardiovascular risk factors should be aggressively managed in all patients 1, 2

• Smoking cessation should be strongly encouraged 2

• Monitor for acquired von Willebrand disease in patients with extreme thrombocytosis 1

• Young patients should use hydroxyurea with caution due to potential long-term leukemogenic risk 2, 3

• Monitor for hydroxyurea side effects including 3, 6:

  • Mucocutaneous manifestations
  • Leg ulcers
  • GI symptoms
  • Pulmonary toxicity

• Resistance or intolerance to hydroxyurea requires switching to second-line therapy 3:

  • Anagrelide for ET 2, 3
  • Interferon-alpha for PV 2, 3
  • Ruxolitinib for resistant/intolerant PV 3

• Thrombotic complications may require both cytoreductive therapy and antithrombotic treatment 7, 8