PRIMARY MYELOFIBROSIS/ MYELOFIBROSIS WITH MYELOID METAPLASIA

Myelofibrosis is a myeloproliferative neoplasm characterized by splenomegaly, teardrop-shaped red blood cells, leukoerythrobastic changes (nucleated red blood cells and immature granulocytes), and a hypercellular bone marrow.  Bone marrow aspiration is often unrewarding (dry tap) and biopsy is required to establish the diagnosis. Bone marrow biopsy is characterized by hypercellularity, osteosclerosis, and collagen fibrosis. Common presenting symptoms include fatigue, night sweats, pruritus, weight loss, and bone pain. Cases may be complicated by either arterial or venous thrombosis. This disorder may be either primary or occur as secondary disease following either essential thrombocytosis or polycythemia vera.

This disorder should be suspected in patients with progressive anemia and splenomegaly. The anemia indices are normochromic and normocytic to macrocytic. Characteristic teardrop-shaped red blood cells, nucleated red blood cells, immature granulocytes, megakaryocte fragments and giant platelets are noted on peripheral smear examination. Both the white blood cell count and the platelet count are variable; however, basophils are usually increased. While platelet counts may be variable at the time of disease onset, as the disease progresses, thrombocytopenia is common.  Approximately 50% of cases of myelofibrosis are associated with the Janus kinase-2 V617F (JAK-2) mutation.

The World Health Organization (WHO) has created both major and minor diagnostic criteria. Three of the major criteria are required for diagnosis and include: atypical megakaryocytes plus fibrotic marrow, the exclusion of other myeloproliferative neoplasms (chronic myelogenous leukemia, essential thrombocytosis, and polycythemia vera), the presence of the JAK2 V617F mutation, and the exclusion of other causes of marrow fibrosis. Two minor criteria are required to establish the diagnosis and include: an elevated lactate dehydrogenase level, leukoerythroblastosis (nucleated red blood cells and immature granulocytes), anemia, and/or splenomegaly.

Hematology consultation is prudent to direct treatment once the diagnosis is established. Various treatment options include: observation for asymptomatic disease without significant anemia or splenomegaly; individual therapy for anemia (androgens, danazol, corticsteroids, Epogen or Procrtit, thalidomide or lenalidomide), thrombocytosis (hydroxyurea), leukocytosis (hydroxyurea) and/or splenomegaly (hydroxyurea, oral alkylators, immunomodulatory agents, interferons, splenectomy or radiation therapy); or allogenic bone marrow transplantation. Antiplatelet therapy or anticoagulants can be added if the case is complicated by either arterial or venous thrombotic events, respectively.