Myeloproliferative neoplasms

Classic BCR::ABL1-negative MPNs include polycythemia vera (PV), essential thrombocythemia (ET) and primary myelofibrosis. Myelofibrosis can also develop after PV or ET. Chronic myeloid leukemia has a different BCR::ABL1-driven pathway and is covered separately.

The work-up combines blood-count trends, marrow morphology, fibrosis grade, JAK2/CALR/MPL testing and appropriate exclusion of other causes. Iron deficiency, inflammation or hypoxia can distort the picture. ET must be distinguished from prefibrotic primary myelofibrosis; a high platelet count alone cannot do that.

For PV and ET, previous thrombosis, age, molecular findings and cardiovascular factors help estimate vascular risk. Very high platelets can also increase bleeding through acquired von Willebrand dysfunction. Disease-progression risk is a separate question from the immediate risk of a clot.

Myelofibrosis assessment considers anemia, blasts, symptoms, cytogenetics and mutations. DIPSS or molecular models may be used for primary disease, and MYSEC-PM for post-PV/ET myelofibrosis. Night sweats, weight loss, itching, fatigue and early satiety deserve direct assessment, even when counts appear stable.

PV management commonly targets hematocrit below 45%, using phlebotomy and, when indicated, cytoreduction. Low-dose aspirin is considered when appropriate without a bleeding contraindication. Hydroxyurea, interferon-based treatment and selected later-line options are chosen according to risk, symptoms, tolerance and local indications.

Rusfertide (Mimrylo) is now US-approved for erythrocytosis in adults with PV. This hepcidin mimetic restricts iron availability for red-cell production; VERIFY tested it in patients still needing frequent phlebotomy despite standard care. Reduced phlebotomy burden does not establish eradication of the clone or elimination of thrombosis and transformation risk.

Iron deficiency and its symptoms need a coordinated plan; do not independently replace iron or stop prescribed phlebotomy, because that can change red-cell production and control.

Treatment is risk-adapted rather than driven by platelet count alone. Antiplatelet treatment and cytoreduction are considered according to thrombosis risk, symptoms and bleeding assessment. Acquired von Willebrand dysfunction, active bleeding and other contraindications can change the aspirin decision.

Ropeginterferon alfa-2b now has a US adult ET indication. SURPASS ET compared it with anagrelide in high-risk, hydroxyurea-intolerant or resistant patients with leukocytosis and favored ropeginterferon on its durable-response endpoint. This selected trial population should not be presented as proof that every newly diagnosed ET patient needs this drug.

Pregnancy planning, surgery and anticoagulation require a separate individualized plan. Interferon and other cytoreductive drugs differ in suitability; patients should discuss these situations before changing medication.

JAK inhibitors can reduce splenomegaly and symptoms in appropriate patients. Choice among ruxolitinib, fedratinib, momelotinib or pacritinib depends on indication, platelet count, anemia, previous therapy and comorbidity. A JAK2 mutation is not required for every JAK-inhibitor use; the pathway can be active through other drivers.

Momelotinib’s US indication covers intermediate- or high-risk primary or secondary myelofibrosis in adults with anemia. Pacritinib’s US indication covers intermediate- or high-risk primary or secondary disease with platelets below 50 × 10⁹/L. These are distinct clinical niches, not interchangeable claims of superiority.

Anemia management may include transfusions and selected anemia-directed approaches after reviewing iron, vitamins, hemolysis and treatment effects. Do not abruptly stop a JAK inhibitor without a plan; symptoms and inflammatory complications can rebound.

Allogeneic transplantation is the established potentially curative option for myelofibrosis. Discuss it before severe deterioration in suitable higher-risk patients. Disease risk, transplant risk, donor options, spleen burden and the patient’s priorities are assessed together; improving symptoms on a JAK inhibitor does not automatically remove the transplant question.

Rising blasts, new cytopenias, increasing spleen size or a new need for transfusions can trigger marrow reassessment. Accelerated or blast-phase transformation requires an urgent specialized strategy, often involving AML-directed or investigational therapy and assessment for transplant after disease control.

Follow-up should track counts, spleen findings, symptoms, thrombosis or bleeding and drug-specific toxicity. Molecular responses can be informative, especially in research and after transplant, but a lower mutation burden is not by itself proof of cure. Rusfertide’s approval includes ongoing long-term safety evaluation of vascular and disease-evolution outcomes.

Sudden weakness, speech or vision changes, chest pain, acute breathlessness, a painful swollen limb or major bleeding needs emergency assessment. Severe new abdominal pain can also signal vascular or splenic complications rather than an ordinary treatment side effect.

Bring the marrow report with fibrosis grade, mutation and cytogenetic results, longitudinal counts, thrombosis and bleeding history, phlebotomy/transfusion records, spleen imaging and all prior medicines. Ask whether the proposed treatment chiefly reduces vascular risk, improves symptoms or changes transplant timing, and how success will be measured.