myelofibrosis

Myelofibrosis is a myeloproliferative neoplasm characterized by replacement of the bone marrow with fibrous tissue, leading to ineffective hematopoiesis and extramedullary hematopoiesis. There are two main forms: primary myelofibrosis (PMF) and secondary myelofibrosis that develops after long-standing polycythemia vera or essential thrombocythemia.

The disease arises from clonal proliferation of hematopoietic stem cells with recurrent mutations, most commonly JAK2 V617F, CALR, or MPL. In PMF, these mutations coexist with bone marrow fibrosis driven by cytokines released by abnormal megakaryocytes. The resulting fibrotic marrow disrupts normal blood cell production and promotes hematopoiesis outside the marrow, notably in the spleen.

Clinical features include fatigue, weakness, anemia, early satiety from splenomegaly, abdominal fullness, night sweats, and weight loss. Splenomegaly is common and can cause abdominal discomfort. Laboratory findings often show anemia with variable white blood cell and platelet counts, leukoerythroblastosis, and teardrop-shaped red cells; LDH is frequently elevated.

Diagnosis relies on bone marrow biopsy showing reticulin or collagen fibrosis, supported by molecular testing for JAK2, CALR, and MPL mutations. Exclusion of other causes of marrow fibrosis is needed, and imaging may assess splenomegaly.

Prognosis varies; risk stratification schemes such as IPSS or DIPSS guide management. Allogeneic stem cell transplantation is potentially curative but suitable only for select patients. Many patients receive supportive care, including transfusions and symptom-directed therapy. JAK inhibitors like ruxolitinib or fedratinib can improve splenomegaly and constitutional symptoms. Regular follow-up is important to monitor disease progression and complications.