What is the recommended treatment for patients with JAK2 V617F mutation and neutrophilia?

Treatment of JAK2 V617F Mutation with Neutrophilia

For patients with JAK2 V617F mutation and neutrophilia, hydroxyurea is recommended as first-line cytoreductive therapy, with interferon-α preferred in younger patients (especially <40 years) to reduce thrombotic risk and normalize blood counts. 1

Risk Stratification and Initial Management

• JAK2 V617F mutation with neutrophilia should be evaluated in the context of myeloproliferative neoplasms (MPNs), with treatment decisions based on risk stratification 2, 1
• High-risk patients (age >60 years and/or history of thrombosis) should receive cytoreductive therapy with hydroxyurea as first-line treatment 2, 1
• Low-dose aspirin (100mg daily) should be administered to all patients without contraindications to reduce thrombotic risk 1
• Aggressive management of cardiovascular risk factors and smoking cessation are essential components of treatment 1

Specific Treatment Recommendations

• Hydroxyurea (starting dose 500mg twice daily) is the preferred cytoreductive agent for older patients (>40 years) 2, 1
• Interferon-α is recommended for younger patients (<40 years), particularly women of childbearing age, as it lacks leukemogenic potential 2, 1
• For patients with JAK2 V617F-positive chronic neutrophilic leukemia specifically, interferon-α has shown effectiveness in controlling neutrophil counts 3
• Target hematocrit should be maintained below 45% in cases where polycythemia is present 4

Special Considerations

• In cases of extreme thrombocytosis (>1,500 × 10^9/L), cytoreductive therapy should be initiated regardless of other risk factors 1
• For patients with thrombotic events, anticoagulation with low molecular weight heparin followed by long-term oral anticoagulation should be considered 1
• JAK2 V617F mutation is a risk factor for splanchnic vein thrombosis, requiring vigilance for this complication 2
• In cases of resistance or intolerance to hydroxyurea, second-line options include anagrelide or pegylated interferon 2, 1

Monitoring and Follow-up

• Regular complete blood counts should be performed to assess response to therapy and monitor for cytopenias 1
• Response should be evaluated by normalization of blood counts (particularly neutrophil counts) and resolution of disease symptoms 1
• Patients should be monitored for development of splenomegaly, which may require adjustment of therapy 5
• Resistance to hydroxyurea is defined as failure to reduce massive splenomegaly, uncontrolled myeloproliferation, or need for phlebotomy after 3 months of adequate dosing 4

Evidence from Case Reports

• Case reports of JAK2 V617F-positive chronic neutrophilic leukemia have shown good response to interferon-α, with reduction of neutrophil counts to normal range 3, 6
• Some patients with JAK2 V617F-positive neutrophilia have shown prolonged survival with appropriate management 7
• Combination therapy with prednisolone and rituximab has been reported effective in managing complications in a patient with JAK2 V617F-positive chronic neutrophilic leukemia 8

Potential Complications

• Patients with JAK2 V617F mutation and neutrophilia are at increased risk for thrombotic events, particularly in splanchnic vessels 2
• Hypersplenism may develop and contribute to cytopenias, requiring adjustment of therapy 5
• Disease progression to more aggressive forms should be monitored, with prompt adjustment of therapy if needed 2