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

Initial Treatment Approach for Myeloproliferative Neoplasms (MPNs)

The initial treatment approach for myeloproliferative neoplasms should be based on risk stratification, with high-risk patients receiving cytoreductive therapy plus aspirin, and low-risk patients receiving observation or phlebotomy (for PV) plus aspirin. 1

Classification of MPNs

• Philadelphia-negative classical MPNs include polycythemia vera (PV), essential thrombocythemia (ET), and myelofibrosis (MF) 1
• Diagnosis requires meeting specific WHO criteria including molecular testing for driver mutations (JAK2, CALR, or MPL) 1
• The presence of specific mutations has prognostic significance, with CALR mutations generally conferring better outcomes than JAK2 mutations or "triple-negative" status 1

Risk Stratification

For PV and ET:

• High-risk: Age >60 years OR history of previous thrombosis 2
• Additional risk factors: Extreme thrombocytosis (>1500 × 10^9/L), cardiovascular risk factors, leukocytosis 1, 2

For Myelofibrosis:

• Use International Prognostic Scoring System (IPSS) at diagnosis 1
• Use Dynamic IPSS (DIPSS) during disease course 2
• Consider cytogenetics and transfusion status in addition to scoring systems 2

Initial Treatment Approach by Disease Type

Polycythemia Vera (PV):

• Low-risk patients:

  • Phlebotomy to maintain hematocrit <45% 2
  • Low-dose aspirin (81-100 mg daily) 2
  • Monitor for disease progression 1

• High-risk patients:

  • Phlebotomy to maintain hematocrit <45% 2
  • Low-dose aspirin (81-100 mg daily) 2
  • Cytoreductive therapy with hydroxyurea as first-line 2
  • Interferon-alpha as alternative first-line, especially in younger patients 1

Essential Thrombocythemia (ET):

• Low-risk patients:

  • Observation with regular monitoring 1
  • Low-dose aspirin if no contraindications 2

• High-risk patients:

  • Cytoreductive therapy with hydroxyurea as first-line 2
  • Target platelet count in normal range while monitoring for cytopenias 3
  • Low-dose aspirin if no contraindications 2

Primary Myelofibrosis (PMF):

• Low-risk/Intermediate-1 risk:

  • Observation if asymptomatic 1
  • Ruxolitinib if symptomatic (especially with significant splenomegaly) 1

• Intermediate-2/High-risk:

  • Allogeneic stem cell transplantation for eligible patients 1
  • Ruxolitinib for symptomatic splenomegaly in transplant-ineligible patients 1
  • Supportive care for anemia and other cytopenias 1

Special Considerations

Thrombocytopenia Management:

• For platelet count >50 × 10^9/L: Continue full therapeutic anticoagulation if indicated 3
• For platelet count 25-50 × 10^9/L: Modify anticoagulation dose to 50% or prophylactic dose 3
• For platelet count <25 × 10^9/L: Consider withholding anticoagulation unless high thrombotic risk 3

Splanchnic Vein Thrombosis:

• Low molecular weight heparin followed by long-term oral anticoagulation 1
• Target INR 2.0-3.0 1
• For patients with thrombocytosis, use hydroxyurea to restore platelet count to <400 × 10^9/L 1

Pregnancy:

• High-risk features include previous thrombosis, hemorrhage, or pregnancy complications 1
• Low-dose aspirin throughout pregnancy (unless bleeding) 1
• Consider low molecular weight heparin for high-risk patients 1
• If platelet count ≥1,500 × 10^9/L, consider interferon-alpha 1

Monitoring Response to Treatment

• Regular assessment of blood counts to monitor response and detect cytopenias 2
• Use Myeloproliferative Neoplasm Symptom Assessment Form (MPN-SAF) to assess symptom burden 1
• Monitor for disease progression with bone marrow examination as clinically indicated 1
• For patients on hydroxyurea, monitor for potential side effects including secondary malignancies 4

Common Pitfalls to Avoid

• Failure to perform molecular testing (JAK2, CALR, MPL) for accurate diagnosis 1
• Overlooking splanchnic vein thrombosis in patients with abdominal symptoms 1
• Not recognizing that hydroxyurea can cause pulmonary toxicity, including interstitial lung disease 4
• Inadequate monitoring for transformation to myelofibrosis or acute leukemia 1
• Using live vaccines in patients taking hydroxyurea 4