Myelofibrosis

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 seen 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 less than 2 of 100,000 people in the United States. It occurs most commonly among people between the ages of 50 and 70.

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; tuberculosis; or bone infections. People who have been exposed to certain toxic substances, such as benzene and radiation, are at increased risk of developing myelofibrosis.

Symptoms, Complications, and Diagnosis

Often, myelofibrosis produces no symptoms for years. Eventually, anemia becomes severe enough to cause weakness, fatigue, 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. 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. Enlargement of these organs may cause pain in the abdomen and may lead to abnormally high blood pressure in certain veins (portal hypertension (see Section 10, Chapter 135)) and bleeding from varicose veins in the esophagus (esophageal varices) (see Section 9, Chapter 132 and Section 10, Chapter 135).

Anemia and the misshapen, immature red blood cells, seen in blood samples viewed under a microscope, suggest myelofibrosis. However, a bone marrow biopsy (see Section 14, Chapter 170) is needed to confirm the diagnosis.

Prognosis and Treatment

Because myelofibrosis generally progresses slowly, people who have it usually live for 10 years or longer, but outcomes are determined by how well the bone marrow functions. Occasionally, however, the disorder worsens rapidly. This rapidly progressive form, called malignant myelofibrosis or acute myelofibrosis, is a type of cancer involving uncontrolled growth of cells that would normally develop into platelets.

No available treatment can effectively reverse or permanently slow the progression of myelofibrosis. Treatment aims to delay and relieve complications.

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 others, blood transfusions are needed to treat the anemia. 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.

Bone marrow or stem cell transplantation is sometimes offered to people who are in otherwise good health and who have an appropriate matched donor (see Section 16, Chapter 187). A transplant is the only treatment available that may cure myelofibrosis, but it also has significant risks associated with it.