Myelofibrosis is a disorder in which fibrous tissue replaces the blood-producing cells in the bone marrow, resulting in abnormally shaped red blood cells, anemia, and an enlarged spleen.
In normal bone marrow, cells called fibroblasts produce fibrous (connective) tissue that supports the blood-producing cells. In myelofibrosis, the fibroblasts produce too much fibrous tissue, which crowds out the blood-producing cells. Consequently, red blood cell production decreases, fewer red blood cells are released into the bloodstream, and anemia develops, becoming progressively more severe. In addition, many of these red blood cells are immature or misshapen. Variable numbers of immature white blood cells and platelets also may be present in the blood. As myelofibrosis progresses, the number of white blood cells may increase or decrease, and the number of platelets typically decreases.
Myelofibrosis is rare, affecting fewer than 2 of 100,000 people in the United States. It occurs with a peak incidence at age 76.
Myelofibrosis may develop on its own (in which case it is also called idiopathic myelofibrosis or agnogenic myeloid metaplasia) or may accompany other blood disorders, such as chronic myelocytic leukemia, polycythemia vera, thrombocythemia, multiple myeloma, lymphoma, and myelodysplasia. It may also occur in people with tuberculosis, pulmonary hypertension, systemic lupus erythematosus (lupus), and systemic sclerosis (scleroderma) and in people in whom a cancer has spread to the bones.
Symptoms, Complications, and Diagnosis
Often, myelofibrosis produces no symptoms for years. However, in some people it rapidly leads to anemia, low levels of platelets in the blood, or leukemia. Eventually, anemia becomes severe enough to cause weakness, tiredness, weight loss, and a general feeling of illness (malaise). Fever and night sweats may occur. With the reduced number of white blood cells, the body is at risk for infections, so people often have frequent infections. With the reduced number of platelets, the body is at risk for bleeding.
The liver and spleen often enlarge as they try to take over some of the job of making blood cells. The spleen also destroys abnormal red cells and platelets made in the bone marrow. The destruction of so many red blood cells and platelets contributes to the spleen enlargement. Enlargement of the liver and spleen may cause pain in the abdomen and may lead to abnormally high blood pressure in certain veins (portal hypertension—see see Portal Hypertension) and bleeding from varicose veins in the esophagus (esophageal varices—see see Portal Hypertension).
Anemia and the misshapen, immature red blood cells, seen in blood samples viewed under a microscope, suggest myelofibrosis. However, a bone marrow biopsy (see see Bone Marrow Examination) is needed to confirm the diagnosis.
Prognosis and Treatment
Because myelofibrosis generally progresses slowly, people who have it may live for 10 years or longer, but outcomes are determined by how well the bone marrow functions. Occasionally, the disorder worsens rapidly. Treatment aims to delay the progression of the disorder and to relieve complications. However, only stem cell transplantation can cure the disorder.
The combination of androgen (a male sex hormone) and prednisone temporarily lessens the severity of the anemia in about one third of people with myelofibrosis. In a few people, red blood cell production can be stimulated with erythropoietin or darbepoietin, drugs that stimulate the bone marrow to produce red blood cells. In other people, blood transfusions are needed to treat the anemia. Bacterial infections are treated with antibiotics.
Hydroxyurea, a chemotherapy drug, or interferon-alpha, a drug that affects the immune system, may decrease the size of the liver or spleen, but either drug may worsen the anemia. Rarely, the spleen becomes extremely large and painful and may have to be removed. Removal of the spleen may increase the number of red blood cells and reduce the need for transfusions.
Stem cell (bone marrow) transplantation is sometimes offered to people who are in otherwise good health and who have an appropriate matched donor (see see Stem Cell Transplantation). A transplant is the only treatment available that may cure myelofibrosis, but it also has significant risks.
Last full review/revision July 2008 by Josef T. Prchal, MD