Myelofibrosis

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    • Myelofibrosis (myelofibrosis with myeloid metaplasia, agnogenic myeloid metaplasia)
    • a myeloproliferative disorder characterized by fibrosis of the bone marrow, splenomegaly, and a leukoerythroblastic peripheral blood picture with teardrop poikilocytosis (MCQ)
    • In response to bone marrow fibrosis, extramedullary hematopoiesis takes place in the liver, spleen, and lymph nodes.
    • abnormalities of JAK2 signaling pathways may be involved in the pathogenesis. (MCQ)
    • Clinical Findings
      • Myelofibrosis develops in adults over age 50 years and is usually insidious in onset.
      • Patients most commonly present with fatigue due to anemia or abdominal fullness related to splenomegaly. (MCQ)
      • On examination, splenomegaly is almost invariably present and is commonly massive.
      • The liver is enlarged in more than 50% of cases.
      • Anemia becomes severe, requiring transfusion.
      • Progressive thrombocytopenia leads to bleeding.
      • The spleen continues to enlarge, which leads to early satiety.
      • Painful episodes of splenic infarction may occur.
      • Late in the course, the patient becomes cachectic and may experience severe bone pain, especially in the upper legs.
      • Hematopoiesis in the liver leads to portal hypertension with ascites, esophageal varices
      • transverse myelitis is caused by myelopoiesis in the epidural space.
    • Laboratory Findings       .       ,   { ,.
      • Patients are almost invariably anemic at presentation
      • The peripheral blood smear is dramatic, with significant poikilocytosis and numerous teardrop forms in the red cell line.
      • Nucleated red blood cells are present and the myeloid series is shifted, with imma¬ture forms including a small percentage of promyelocytes or myeloblasts.
      • Platelet morphology may be bizarre, and giant degranulated platelet forms (megakaryocyte frag¬ments) may be seen.
      • The triad of teardrop poikilocytosis, leukoerythroblastic blood, and giant abnormal platelets is highly suggestive of myelofibrosis. (MCQ)
      • The bone marrow usually cannot be aspirated (dry tap), though early in the course of the disease it is hypercellular, with a marked increase in megakaryocytes. (MCQ)
      • Fibrosis at this stage is detected by a silver stain demonstrating increased reticulin fibers(MCQ)
      • Later, biopsy reveals more severe fibrosis, with eventual replacement of hematopoietic precursors by collagen
    • Differential Diagnosis
      • A leukoerythroblastic blood picture from other causes may be seen in response to severe infection, inflammation, or infiltrative bone marrow processes. However, teardrop poikilocytosis and giant abnormal platelet forms will not be present. (MCQ)
      • Bone marrow fibrosis may be seen in metastatic carcinoma, Hodgkin disease, and hairy cell leukemia. (MCQ)
      • Concerning other myeloproliferative disorders, chronic myeloid leukemia is diagnosed when there is marked leukocytosis, normal red blood cell morphology, and the presence of the bcr/abl fusion gene
      • Polycythemia vera is characterized by an elevated hematocrit.
      • Essential throm-bocytosis shows predominant platelet count elevations.
    • Treatment Course & Prognosis
      • Thalidomide(MCQ)
        • has produced definite responses with acceptable toxicity
        • lenalidomide has at least the same efficacy with less toxicity.
        • Clinical trials testing the effect of JAK2 inhibitors are currently being performed
      • Allogeneic bone marrow transplantation has been performed successfully with 50% long-term survival and should be considered in younger patients. (MCQ)
      • Splenectomy is not routinely performed but is indicated for splenic enlargement causing recurrent painful episodes, severe thrombocytopenia, or an unacceptable transfusion requirement.
      • Median survival from time of diagnosis is approximately 5 years(MCQ)


    What is primary myelofibrosis?
    Learn what is primary myelofibrosis as well as how to identify its signs and symptoms, diagnose it, and treat it
    JAK2 Inhibition in the Treatment of Myelofibrosis
    The mechanism of action of CYT387, a novel JAK1 and JAK2 inhibitor, in the treatment of myeloproliferative neoplasms. Janus kinases frequently mediate signaling in several diseases. Animation done for Toronto biotechnology company, YM Biosciences.
    Myelofibrosis
    Myelofibrosis, also known as osteomyelofibrosis, is a rare bone marrow cancer. It is currently classified as a myeloproliferative neoplasm, in which the proliferation of an abnormal clone of hematopoietic progenitor cells in the bone marrow and other sites results in fibrosis, or the replacement of the marrow with collagenous connective tissue fibers. The term myelofibrosis alone usually refers to primary myelofibrosis (PMF) (chronic idiopathic myelofibrosis [cIMF]), the idiopathic form of the disease, in contrast with myelofibrosis secondary to polycythemia vera or essential thrombocythaemia. Myelofibrosis is a form of myeloid metaplasia, and often the two terms are used synonymously. Agnogenic myeloid metaplasia and myelofibrosis with myeloid metaplasia (MMM) also overlap on the same spectrum.

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    Histopathology Bone Marrow–Chronic idiopathic myelofibrosis
    Histopathology Bone Marrow–Chronic idiopathic myelofibrosis