(Idiopathic myelofibrosis, myelofibrosis, myeloid metaplasia with myelofibrosis)

The primary myelofibrosis (PMF) is a chronic, usually idiopathic disease that is characterized by bone marrow fibrosis, splenomegaly, and anemia with nucleated and teardrop erythrocytes. Diagnosis requires a bone marrow examination and can cause a myelofibrosis (secondary myelofibrosis) to the exclusion of other diseases. Treatment is often supportive but JAK2 inhibitors such Ruxolitinib can reduce the symptoms and a stem cell transplant can make the fibrosis reversed.

The primary myelofibrosis (PMF) is a chronic, usually idiopathic disease that is characterized by bone marrow fibrosis, splenomegaly, and anemia with nucleated and teardrop erythrocytes. Diagnosis requires a bone marrow examination and can cause a myelofibrosis (secondary myelofibrosis) to the exclusion of other diseases. Treatment is often supportive but JAK2 inhibitors such Ruxolitinib can reduce the symptoms and a stem cell transplant can make the fibrosis reversed. Pathophysiology of myelofibrosis are excessive bone marrow fibrosis and the loss of hematopoietic stem cells. As a result, there is a significant increase in extramedullary hematopoiesis (mainly in the liver and spleen with a significant increase in size of both organs). The disease may be primary or secondary occur as a result of a number of hematological, malignant or non-malignant diseases (see table: associated with myelofibrosis disease). A primary myelofibrosis occurs more often as a secondary myelofibrosis and is due to a change of a neoplastic multipotent bone marrow stem cell. The daughter cells stimulate bone marrow fibroblasts (which are not changed neoplastic) to the excessive production of collagen to. The highest incidence of primary myelofibrosis is found between 50 and 70 years of age. In primary myelofibrosis large amounts of nucleated red blood cells (normoblasts) and granulocytes in the blood flushed (Leukoerythroblastose). This may be associated with an increase in LDH value. Ultimately, it comes to bone marrow failure with subsequent anemia and thrombocytopenia. About 10% of patients develop acute leukemia that does not respond to chemotherapy. The rare variant of a malignant or acute myelofibrosis shows a significantly accelerated clinical course. It is best classified as acute megakaryoblastic. With myelofibrosis associated diseases Group Examples malignancies tumor with bone marrow metastases Hodgkin’s lymphoma leukemias (especially chronic myeloid leukemia and hairy cell leukemia) Multiple myeloma Non-Hodgkin lymphoma polycythemia vera (15-30% of patients in the progressive late phase) Essential thrombocythemia infection osteomyelitis tuberculosis Primary pulmonary hypertension – Toxins benzene thorium X-rays or ?-radiation autoimmune diseases (rarely) Systemic Lupus Erythematosus Systemic sclerosis symptoms and discomfort in many patients is the Myelofibrosis asymptomatic. Others have symptoms of anemia, splenomegaly, or – in advanced stages – malaise, weight loss, fever or splenic infarction. A lot of the patients showed hepatomegaly. Lymphadenopathy is rare. Diagnostic blood count and peripheral blood smear bone marrow examination a primary myelofibrosis should be considered in patients with splenomegaly, Milzinfarkten, anemia or unclear LDH increases. When in doubt, a complete blood count should be created and peripheral smears and bone marrow examination incl. Cytogenetic and molecular genetic tests will be done. by the bone marrow examination, if a Myelofibrosis is detected (for example, by increased fibroblasts and collagen in the Retikulinf√§rbung, osteosclerosis.), other diseases that may be associated with myelofibrosis were (see Table: With myelofibrosis associated diseases), clinical by suitable and laboratory tests are excluded. Typically occurs anemia, which is usually stronger in the course. The blood cell morphology is variable. Poikilocytes Reticulocytosis and polychromatophilia may occur; characteristic drop-shaped erythrocytes (Dakryozyten). Nucleated red blood cell and neutrophil precursors are usually present in the peripheral blood. The white blood cell count is usually increased, but also very variable; a low white blood cell count is an indication of a poor prognosis. Neutrophils are usually immature, and even without the occurrence of acute leukemia myeloblasts may be detectable. The platelet count may be increased at the beginning, be normal or reduced, however prevails in the course of the disease, thrombocytopenia. In difficult diagnosis, the number of CD34 + cells can be determined in the peripheral blood. The levels are significantly elevated in patients with primary myelofibrosis. Often one finds Punctio sicca. As is necessary for the diagnosis of evidence of bone marrow fibrosis, but this must be not evenly distributed, this should be repeated elsewhere in non groundbreaking first biopsy. About 50% of patients have a JAK2 mutation. Some patients have a mutation of the calreticulin gene. Prognosis The mean survival time of the onset of the disease for 5 years, with the variation width is large; some patients have a rapidly progressive disease with short survival time, with others, the initial diagnosis is delayed. Poor prognostic markers are a hemoglobin <10 g / dl, obtained transfusions, leukocytosis and leukopenia, blasts in the differential blood count and a platelet count <100,000 / ul. Patients in the most unfavorable risk group usually have a survival time of <1 year. With the exception of allogeneic stem cell transplantation, the underlying processes through therapy can not reverse nor control. Symptomatic treatment therapy Occasionally allogeneic stem cell Sometimes a JAK2 inhibitor, ruxolitinib The treatment is based on the symptoms and complications. Androgens, splenectomy, chemotherapy and Milzembolisation and irradiation are used palliative. A temporary administration of low-dose corticosteroids can relieve symptoms. In young patients with advanced disease allogeneic stem cell transplantation may be helpful. Even in older patients nichtmyeloablative allogeneic stem cell transplantation has already been applied. Inhibitors of JAK signaling pathway appear to have a significant impact on the splenomegaly and the symptoms; Ruxolitinib is available at the moment and other inhibitors are clinically tested. JAK inhibitors are independent of whether a JAK2 mutation is present, effective. The dismissal of Ruxolitinib must be done with caution as a withdrawal syndrome has been observed; deprivation can lead to significant deterioration of the symptoms, which are partly due to splenomegaly. Important Points When myelofibrosis are excessive bone marrow fibrosis and the loss of hematopoietic stem cells. As a result, there is a significant increase in extramedullary hematopoiesis (mainly in the liver and spleen with a significant increase in size of both organs). Myelofibrosis is often primarily, but can also occur secondary as a result of a number of hematological, malignant or non-malignant diseases. The primary myelofibrosis is caused by the neoplastic transformation of a multipotential bone marrow stem cell; progeny cells stimulate bone marrow fibroblast to secrete excessive collagen. The diagnosis is made on the basis of the blood count, peripheral blood smear and bone marrow examination. The average survival rate is 5 years after the onset of the disease, but there are strong variations. A supportive care, and sometimes an allogeneic stem cell transplantation or a JAK pathway inhibitor (z. B. Ruxolitinib) are applied.

Health Life Media Team

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