Myelofibrosis: causes, symptoms, diagnosis, treatment

Myelofibrosis (idiopathic myeloid metaplasia, myelofibrosis with myeloid metaplasia) is a chronic and usually idiopathic disease characterized by bone marrow fibrosis, splenomegaly, and anemia with immature and teardrop-shaped red blood cells. Diagnosis requires bone marrow examination and exclusion of other causes that can cause secondary myelofibrosis. Supportive treatment is usually given.

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Epidemiology

The peak incidence of idiopathic myelofibrosis occurs between the ages of 50 and 70 years.

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Causes myelofibrosis

Myelofibrosis is characterized by fibrous degeneration of the bone marrow with loss of hematopoietic cells and subsequent development of extramedullary hematopoiesis (mainly in the liver and spleen, the size of which increases significantly). This pathology is usually a primary disease, which is probably caused by neoplastic transformation of multipotent stem cells of the bone marrow - these stem cells stimulate bone marrow fibroblasts (this process is not part of neoplastic transformation) to increased collagen formation. Myelofibrosis can also occur due to various hematological, oncological and infectious diseases. In addition, myelofibrosis can be a complication of chronic myelogenous leukemia and occurs in 15-30% of patients with true polycythemia and a long course of the disease. A large number of immature erythrocytes and granulocytes enter the bloodstream (leukoerythroblastosis), which can be accompanied by an increase in the activity of LDH in the blood. Myelofibrosis results in bone marrow failure with anemia and thrombocytopenia. A rarer variant of this disease is malignant or acute myelofibrosis, which is characterized by more rapid progression; it is possible that this form of the disease is actually a true megakaryocytic leukemia.

Conditions associated with myelofibrosis

State	Example
Malignant diseases	Leukemia, polycythemia vera, multiple myeloma, Hodgkin's lymphoma (Hodgkin's disease), non-Hodgkin's lymphomas, cancer with metastatic bone marrow lesions
Infections	Tuberculosis, osteomyelitis
Toxins	X-rays or gamma radiation, benzene, thorium dioxide
Autoimmune diseases (rare)	SKV

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Symptoms myelofibrosis

Early stages may be asymptomatic. Splenomegaly may be present; in later stages, patients may complain of general malaise, weight loss, fever, and splenic infarctions may be detected. Hepatomegaly is present in 50% of patients. Lymph node enlargement is occasionally seen, but is not typical of the disease. Rapidly progressive acute leukemia develops in approximately 10% of patients.

Diagnostics myelofibrosis

Idiopathic myelofibrosis should be suspected in patients with splenomegaly, splenic infarction, anemia, or unexplained elevations in LDH levels. If the disease is suspected, a complete blood count and peripheral blood and bone marrow pathology with cytogenetic analysis should be performed. Other disorders associated with myelofibrosis (eg, chronic infections, granulomatous diseases, metastatic cancer, hairy cell leukemia, autoimmune diseases) should be excluded; this is usually done by examining the bone marrow (if there are appropriate clinical and laboratory data).

Blood cells have different morphological structures. Anemia is a characteristic sign of the disease and tends to progress. Erythrocytes are normochromic-normocytic with slight poikilocytosis, in addition, reticulocytosis and polychromatophilia are observed. Nucleated erythrocytes may be found in the peripheral blood. In the late stages of the disease, erythrocytes are deformed and may have the shape of a drop; these changes are quite sufficient to suspect this disease.

The white blood cell count is usually elevated but highly variable. Immature neutrophils are usually present, and blastic forms may be present (even in the absence of acute leukemia). Platelet counts may be high, normal, or low early in the disease; with disease progression, thrombocytopenia tends to occur. The peripheral blood may have elevated progenitor cell levels (as detected by CD34+ cell counts).

Bone marrow aspirate is usually dry. Since bone marrow fibrosis must be detected to confirm the diagnosis, and fibrosis may be unevenly distributed, if the first biopsy is uninformative, it must be repeated elsewhere.

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Treatment myelofibrosis

There is currently no treatment that reverses the process or provides effective control over the disease. Therapy is aimed at eliminating symptoms and treating complications.

Androgens, splenectomy, chemotherapy, and radiation therapy to the spleen are sometimes used to improve the patient's condition. When erythropoietin (EPO) levels are low, corresponding to the degree of anemia, erythropoietin therapy at a dose of 40,000 U subcutaneously once a week may sufficiently increase the hematocrit; otherwise, red blood cell transfusions are necessary. In young patients with advanced disease, allogeneic bone marrow transplantation should be considered.

Forecast

The median survival from the onset of the disease is about 5 years, although in some cases the diagnosis cannot be made immediately. The presence of general symptoms, anemia or certain cytogenetic abnormalities indicate a poor prognosis; in the presence of anemia and some cytogenetic abnormalities, the median survival may decrease to 2 years.

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