Myelofibrose

Myelofibrosis, or myelofibrose, is a chronic myeloproliferative neoplasm characterized by progressive scarring (fibrosis) of the bone marrow. This fibrosis disrupts normal blood cell production, often leading to anemia, enlarged spleen or liver (extramedullary hematopoiesis), fatigue, and constitutional symptoms. Myelofibrosis can be primary (arising on its own) or evolve from other myeloproliferative neoplasms such as polycythemia vera or essential thrombocythemia.

Pathophysiology is driven by clonal proliferation of hematopoietic cells with mutations in the JAK-STAT signaling pathway. Common driver mutations include JAK2 V617F, CALR, and MPL, though other genetic alterations may be present. Abnormal megakaryocytes and cytokine release promote fibroblast activity, leading to bone marrow fibrosis and ineffective hematopoiesis. The disease often features teardrop-shaped red blood cells and a leukoerythroblastic smear.

Diagnosis relies on a combination of blood tests, peripheral smear findings, bone marrow biopsy showing fibrosis, and molecular testing for driver mutations. Exclusion of other causes of marrow fibrosis is important. Prognosis is assessed with scoring systems such as the International Prognostic Scoring System (IPSS) or Dynamic IPSS, which categorize risk and guide management.

Treatment aims to relieve symptoms, control blood counts, and manage complications. There is no cure for most patients except under specific circumstances with allogeneic stem cell transplantation. Therapies include JAK inhibitors (e.g., ruxolitinib, fedratinib) to reduce splenomegaly and symptoms, cytoreductive therapy for abnormal blood counts (such as hydroxyurea), and supportive care with transfusions and iron chelation if needed. Splenectomy or splenotherapy may be considered in selected cases. Ongoing monitoring for progression to acute myeloid leukemia is important.