Primary Myelofibrosis (PMF)

PMF is a chronic myeloproliferative neoplasm characterized by clonal proliferation of hematopoietic stem cells, bone marrow fibrosis, extramedullary hematopoiesis, and cytokine-driven symptoms. It can evolve from polycythemia vera or essential thrombocythemia (post-PV/ET MF).

Symptoms & Signs

• Constitutional symptoms: fatigue, night sweats, weight loss, fever
• Massive splenomegaly causing abdominal discomfort, early satiety
• Anemia, thrombocytopenia, leukocytosis or leukopenia
• Bone pain, pruritus
• Thrombotic or bleeding complications

Diagnosis

• Bone marrow biopsy with megakaryocytic atypia, reticulin/collagen fibrosis
• Peripheral smear showing teardrop cells (dacrocytes), leukoerythroblastic picture
• Molecular testing: JAK2 V617F (~60%), CALR, MPL mutations; next-gen sequencing for high-risk mutations (ASXL1, SRSF2, EZH2, IDH1/2)
• Exclude other causes of marrow fibrosis (metastatic cancer, infection)
• Risk stratification: DIPSS, DIPSS-plus, MIPSS70, GIPSS

Treatment Strategy

Symptom Control & Cytoreduction

• JAK inhibitors (ruxolitinib, fedratinib, pacritinib, momelotinib) reduce splenomegaly and constitutional symptoms
• Monitor for cytopenias, infections, Wernicke's with fedratinib
• Hydroxyurea or pegylated interferon for cytoreduction in select patients
• Androgen therapy or lenalidomide for anemia (variable response)

Anemia Management

• Transfusions, erythropoiesis-stimulating agents (if low EPO)
• Luspatercept (off-label) in clinical trials
• Momelotinib improves anemia by inhibiting ACVR1

Allogeneic Hematopoietic Stem Cell Transplant

• Only curative therapy; consider for patients <70 with intermediate-2/high-risk disease
• Timing balances transplant risk vs disease progression

Supportive Care

• Manage gout, hyperuricemia, bone pain
• Infection prophylaxis when using immunosuppressants/JAK inhibitors
• Splenectomy or splenic irradiation rarely used (risk of portal vein thrombosis)

Monitoring

• CBC every 1–3 months, symptom scores (MPN-SAF), spleen size, mutation burden
• Bone marrow biopsy for disease progression or cytopenias
• Watch for transformation to acute myeloid leukemia (blast phase)

Living with PMF

• Track labs, spleen measurements (imaging or palpation), transfusions, medications, side effects, symptom scores
• Maintain vaccinations (influenza, COVID-19, pneumococcal, shingles) prior to immunosuppression
• Nutritional support for early satiety; mental health counseling for chronic fatigue
• Discuss fertility preservation before cytotoxic therapy

Complications

• Anemia, thrombocytopenia requiring transfusions
• Portal hypertension, variceal bleeding
• Bone pain, osteoporosis
• AML transformation (10–20% at 10 years)
• Infection risk with JAK inhibitors

Research & Future Directions

Next-gen JAK inhibitors, BET inhibitors, BCL-2 inhibitors, and combination regimens targeting inflammatory pathways aim to modify disease course.

Experimental & Emerging Treatments

• PELACARSEN + Ruxolitinib: Targeting epigenetic regulators to reverse fibrosis.
• BCL-xL/BCL-2 inhibitors (navitoclax) combined with ruxolitinib show spleen/symptom improvements.
• Telomerase Inhibitors (imetelstat): Demonstrated survival benefit in relapsed MF.
• Digital Biomarkers: Wearables tracking activity/fatigue correlate with symptom burden and treatment response.

Track PMF with Diagnoza.care

Balance Symptom Relief & Transplant Planning – Log CBC trends, spleen size, MPN-SAF scores, JAK inhibitor dosing, transfusions, anemia therapies, transplant evaluations, imaging, and mental health metrics; capture side effects; and let the AI companion remind you of labs and red flags requiring hematology review.

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Medical Disclaimer: Informational only. Work with your hematologist/MPN center for risk stratification, JAK inhibitor selection, anemia management, and transplant timing. Sources: National Comprehensive Cancer Network, European LeukemiaNet, Myeloproliferative Neoplasm Research Foundation