Primary Myelofibrosis

Primary myelofibrosis (PMF) is a myeloproliferative neoplasm with megakaryocytic proliferation, reticulin or collagen marrow fibrosis, extramedullary haematopoiesis and constitutional symptoms.

• Incidence 0.5 to 1.5 per 100,000, median age 65.

• Drivers: JAK2 V617F (60%), CALR (25%), MPL (8%), triple negative (8%) with high molecular risk mutations (ASXL1, SRSF2, EZH2, IDH1/2).

• Prefibrotic and overt fibrotic phases.

• Scores: DIPSS-Plus and MIPSS70 (for transplant candidates), median survival from 2 to 20 years.

• Complications: massive splenomegaly, anaemia, portal hypertension, thrombosis, leukaemic transformation (10 to 20%).

• Fatigue, weight loss, night sweats, fever, bone pain, pruritus, early satiety, left upper quadrant pain.

• Marked splenomegaly, hepatomegaly, cytopenias, leucoerythroblastic film with teardrop cells.

• Bleeding and thrombosis, gout.

• Blood film with teardrop cells and nucleated red cells; elevated LDH, uric acid.

• Bone marrow biopsy: megakaryocyte atypia, reticulin or collagen fibrosis (grade 2 to 3).

• Driver and high molecular risk mutation panel; cytogenetics.

• Exclude CML, other myeloproliferative neoplasms, MDS, metastatic cancer and infection causing secondary fibrosis.

• Symptom burden score (MPN-SAF), spleen imaging.

• Allogeneic stem cell transplant is the only curative option for intermediate-2 or high risk, fit patients under 70.

• JAK inhibitors for symptomatic splenomegaly or symptoms: ruxolitinib 5 to 20 mg twice daily (dose by platelet count: 15 mg twice daily if platelets 100 to 200; 20 mg if over 200; 5 mg twice daily if 50 to 99), fedratinib 400 mg daily, pacritinib 200 mg twice daily (platelets under 50), momelotinib 200 mg daily (anaemia).

• Anaemia: luspatercept 1 mg/kg, ESA if erythropoietin low, danazol 600 mg daily, prednisolone, immunomodulatory drugs, transfusions.

• Hydroxyurea 15 to 30 mg/kg for proliferative features.

• Splenectomy or splenic radiotherapy (0.1 to 0.5 Gy) for refractory splenomegaly.

• Pelabresib, navitoclax combination under study.

• Thromboprophylaxis with aspirin; supportive care and palliation.

• Monitor blood counts every 1 to 3 months and symptom burden.