myelofibros

Myelofibrosis is a rare myeloproliferative neoplasm characterized by progressive scarring of the bone marrow (myelofibrosis) and disordered hematopoiesis. Primary myelofibrosis is the classic form; it can also develop as a secondary condition arising from other myeloproliferative neoplasms such as essential thrombocythemia or polycythemia vera. Most cases involve activating mutations in the JAK-STAT pathway, such as JAK2, CALR, or MPL.

As the marrow becomes fibrotic, blood cell production is impaired, leading to anemia, fatigue, and low blood counts. The body compensates by expanding hematopoiesis outside the marrow, most notably in the spleen and liver, causing splenomegaly and abdominal fullness. Blood smears may show teardrop-shaped red cells and a leukoerythroblastic picture.

Diagnosis relies on a combination of blood tests, bone marrow biopsy showing fibrosis, and molecular testing for driver mutations. Imaging may document organomegaly. Prognosis is refined with risk scores such as DIPSS or DIPSS-plus to guide treatment decisions.

Treatment is tailored to symptoms and risk. Many patients require supportive care such as blood transfusions; iron chelation if iron overload occurs. JAK inhibitors like ruxolitinib or fedratinib reduce spleen size and symptoms in many patients. Allogeneic hematopoietic stem cell transplantation offers potential cure for selected, younger patients or those with high-risk disease. Some patients may benefit from treatment of anemia or cytopenias with erythropoiesis-stimulating agents or androgens; splenectomy or radiation therapy is rarely used.

Prognosis varies widely depending on risk category and complications. Transformation to acute myeloid leukemia is a known but uncommon risk. The disease is most often diagnosed in older adults, and incidence rises with age.