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Myelofibrosis

By

Jane Liesveld

, MD, James P. Wilmot Cancer Institute, University of Rochester Medical Center

Last full review/revision Sep 2020| Content last modified Sep 2020
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Topic Resources

Myelofibrosis is a disorder in which fibrous tissue in the bone marrow replaces the blood-producing cells, resulting in abnormally shaped red blood cells, anemia, and an enlarged spleen.

  • Myelofibrosis may occur on its own because of certain gene mutations, or it may occur as a result of other blood disorders.

  • People may feel tired and weak, have infections, and bleed easily.

  • Blood tests and a bone marrow biopsy are done for diagnosis.

  • Drugs and other treatments lessen the severity of anemia, increase red blood cell production, and fight infections.

  • Sometimes stem cell transplantation is used.

In normal bone marrow, cells called fibroblasts produce the fibrous (connective) tissue that supports the blood-producing cells. In myelofibrosis, the fibroblasts make too much fibrous tissue, which crowds out the blood-producing cells. When this occurs, some blood-producing cells migrate from the bone marrow to the spleen and liver. Overall, red blood cell production decreases, 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 (thrombocytopenia).

Myelofibrosis is uncommon. It may

  • Develop on its own (called primary myelofibrosis)

  • Accompany another disorder (called secondary myelofibrosis)

Primary myelofibrosis is myelofibrosis that develops on its own, due to certain genetic mutations. It occurs most often between age 50 and 70 years, mostly in men. About half of people who have primary myelofibrosis have a mutation in the Janus kinase 2 (JAK2) gene. This gene controls certain enzymes that are involved in cell growth and the immune response. Other people have a mutation in the gene called calreticulin (CALR), which is involved in making proteins that are needed for proper cell function, or in the thrombopoietin receptor gene (MPL), which is involved in cell growth.

Secondary myelofibrosis occurs as a result of other disorders, particularly other blood disorders such as chronic myeloid leukemia, polycythemia vera, thrombocythemia, multiple myeloma, and lymphoma. It may also occur in people with tuberculosis, pulmonary hypertension, systemic lupus erythematosus (lupus), systemic sclerosis, and HIV infection, and in people in whom a cancer has spread to the bones.

Symptoms

Often, myelofibrosis causes no symptoms for years. However, in some people, myelofibrosis rapidly leads to anemia, low levels of platelets in the blood (thrombocytopenia), or leukemia. Eventually, anemia becomes severe enough to cause weakness, tiredness, weight loss, and a general feeling of illness (malaise). Fever, night sweats, and weight loss may occur. If the number of white blood cells is reduced, the body is at risk for infections, so people may have frequent infections. With the reduced number of platelets, the body is at risk for bleeding. People with secondary myelofibrosis also have symptoms of whatever disorder caused the myelofibrosis.

The liver and spleen enlarge as they try to take over some of the job of making blood cells, but blood cell production is ineffective in these organs and instead just 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) and bleeding from varicose veins in the esophagus (esophageal varices).

Malignant myelofibrosis (sometimes called acute myelofibrosis) is a rare type of myelofibrosis in which levels of red blood cells, white blood cells, and platelets are all decreased. The number of certain immature white blood cells (blast cells) in the bone marrow is increased. Malignant myelofibrosis is considered to be a type of acute leukemia.

Diagnosis

  • Blood tests

  • Bone marrow biopsy

  • Genetic testing

Anemia and the misshapen, immature red blood cells seen in blood samples viewed under a microscope, suggest myelofibrosis. However, a bone marrow biopsy is needed to confirm the diagnosis. Tests for the JAK2, CALR, or MPL mutations are done. Sometimes other tests are needed to distinguish whether other blood disorders are also present such as chronic myeloid leukemia (CML) or mastocytosis.

Prognosis

About half of people who have primary myelofibrosis survive for more than 5 years, but the length of survival varies a great deal from one person to another. Doctors use a system that assigns values to various characteristics of the disorder to help determine prognosis and guide treatment decisions.

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.

Prognosis in secondary myelofibrosis depends in large part on the underlying disorder. Myelofibrosis that occurs after polycythemia vera or essential thrombocythemia typically has a poor prognosis. Prognostic scoring systems have been developed which can help determine prognosis in primary myelofibrosis and in myelofibrosis preceded by polycythemia or essential thrombocythemia.

Treatment

  • Sometimes stem cell transplantation

  • Sometimes ruxolitinib or fedratinib

Stem cell transplantation (bone marrow transplantation) is sometimes used in people who have high-risk primary myelofibrosis (based on their age, symptoms, blood counts, and genetic mutation). Transplantation is the only treatment available that may cure myelofibrosis, but it also has significant risks. Transplantation is often recommended for younger people who have no other serious medical problems and have a suitable donor.

Ruxolitinib, a drug that was developed to inhibit the JAK2 mutation is often the first treatment used. It is also effective in people who have the CALR or MPL mutations because they also activate JAK2 enzyme. It is effective in reducing spleen size and controlling symptoms and may increase overall survival and slow the rate of fibrosis, but it does not reverse existing fibrosis in most cases and can lead to anemia and low platelet counts. Doctors sometimes also give thalidomide together with prednisone, which can help maintain the platelet count and also reduce the size of the spleen. Fedratinib also inhibits the JAK2 mutation and can be used as an alternative to ruxolitinib.

Reducing the size of the spleen tends to relieve symptoms. In addition to ruxolitinib, hydroxyurea, a chemotherapy drug, may decrease the size of the liver or spleen but may worsen anemia and low platelet count. Radiation therapy can decrease the size of the spleen but has only a temporary effect and can cause very low white blood cell counts and infection.

Rarely, the spleen becomes extremely large and painful and may have to be removed, but spleen removal is recommended only after all other measures have been tried. It is not done often in people with primary myelofibrosis due to potential complications such as blood clotting, infection, and shift of blood cell production to other vital organs such as the liver.

The combination of an androgen (a drug with the effects of male sex hormones) such as danazol and prednisone temporarily lessens the severity of the anemia in about one third of people with myelofibrosis, but this treatment is not often used. Erythropoietin, a hormone that stimulates red blood cell production, may improve anemia but also causes enlargement of the spleen. Sometimes erythropoietin is used together with ruxolitinib or fedratinib to prevent enlargement of the spleen. Some people with severe anemia require red blood cell transfusions.

Other drugs are being developed to treat myelofibrosis, so people may want to search for a clinical trial.

More Information

The following is an English-language resource that may be useful. Please note that THE MANUAL is not responsible for the content of this resource.

  • MPN Research Foundation: supports research as well as advocacy and education for people with myeloproliferative neoplasms

Drugs Mentioned In This Article

Generic Name Select Brand Names
HYDREA
THALOMID
JAKAFI
RAYOS
No US brand name
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