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.
(See also Overview of Myeloproliferative Neoplasms Overview of Myeloproliferative Neoplasms In myeloproliferative neoplasms (myelo = bone marrow; proliferative = rapid multiplication; and neoplasm = new abnormal growth, such as a precancer or cancer), the blood-producing cells in the... read more .)
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 Formation of Blood Cells Red blood cells, most white blood cells, and platelets are produced in the bone marrow, the soft fatty tissue inside bone cavities. Two types of white blood cells, T and B cells ( lymphocytes)... read more decreases, and anemia Overview of Anemia Anemia is a condition in which the number of red blood cells is low. Red blood cells contain hemoglobin, a protein that enables them to carry oxygen from the lungs and deliver it to all parts... read more develops, becoming progressively more severe.
In addition, many of these red blood cells are immature or misshapen. Variable numbers of immature white blood cells White Blood Cells The main components of blood include Plasma Red blood cells White blood cells Platelets read more and platelets Platelets The main components of blood include Plasma Red blood cells White blood cells Platelets read more 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 Overview of Thrombocytopenia Thrombocytopenia is a low number of platelets (thrombocytes) in the blood, which increases the risk of bleeding. Thrombocytopenia occurs when the bone marrow makes too few platelets or when... read more ).
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 Chronic Myeloid Leukemia (CML) Chronic myeloid leukemia is a slowly progressing disease in which cells that normally would develop into the types of white blood cells called neutrophils, basophils, eosinophils, and monocytes... read more , polycythemia vera Polycythemia Vera Polycythemia vera is a myeloproliferative neoplasm of the blood-producing cells of the bone marrow that results in overproduction of all types of blood cells. Polycythemia vera is due to mutations... read more , thrombocythemia Essential Thrombocythemia Essential thrombocythemia is a myeloproliferative neoplasm in which excess platelets are produced, leading to abnormal blood clotting or bleeding. The hands and feet may burn, turn red, and... read more , multiple myeloma Multiple Myeloma Multiple myeloma is a cancer of plasma cells in which abnormal plasma cells multiply uncontrollably in the bone marrow and occasionally in other parts of the body. People often have bone pain... read more , and lymphoma Overview of Lymphoma Lymphomas are cancers of lymphocytes, which reside in the lymphatic system and in blood-forming organs. Lymphomas are cancers of a specific type of white blood cells known as lymphocytes. These... read more . It may also occur in people with tuberculosis Tuberculosis (TB) Tuberculosis is a chronic contagious infection caused by the airborne bacteria Mycobacterium tuberculosis. It usually affects the lungs, but almost any organ can be involved. Tuberculosis... read more , pulmonary hypertension Pulmonary Hypertension Pulmonary hypertension is a condition in which blood pressure in the arteries of the lungs (the pulmonary arteries) is abnormally high. Many disorders can cause pulmonary hypertension. People... read more , systemic lupus erythematosus Systemic Lupus Erythematosus (SLE) Systemic lupus erythematosus is a chronic autoimmune inflammatory connective tissue disorder that can involve joints, kidneys, skin, mucous membranes, and blood vessel walls. Problems in the... read more (lupus), systemic sclerosis Systemic Sclerosis Systemic sclerosis is a rare, chronic autoimmune connective tissue disorder characterized by degenerative changes and scarring in the skin, joints, and internal organs and by blood vessel abnormalities... read more , and HIV infection Human Immunodeficiency Virus (HIV) Infection , and in people in whom a cancer has spread to the bones.
Symptoms of Myelofibrosis
Often, myelofibrosis causes no symptoms for years. However, in some people, myelofibrosis rapidly leads to anemia Overview of Anemia Anemia is a condition in which the number of red blood cells is low. Red blood cells contain hemoglobin, a protein that enables them to carry oxygen from the lungs and deliver it to all parts... read more , low levels of platelets in the blood (thrombocytopenia Overview of Thrombocytopenia Thrombocytopenia is a low number of platelets (thrombocytes) in the blood, which increases the risk of bleeding. Thrombocytopenia occurs when the bone marrow makes too few platelets or when... read more ), or leukemia Overview of Leukemia Leukemias are cancers of white blood cells or of cells that develop into white blood cells. White blood cells develop from stem cells in the bone marrow. Sometimes the development goes awry... read more . 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 Portal Hypertension Portal hypertension is abnormally high blood pressure in the portal vein (the large vein that brings blood from the intestine to the liver) and its branches. Cirrhosis (scarring that distorts... read more ) and bleeding from varicose veins in the esophagus (esophageal varices Esophageal Varices Esophageal varices are enlarged veins in the esophagus, which can cause major bleeding. Esophageal varices are caused by high blood pressure in blood vessels in and around the liver (portal... read more ).
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 Overview of Leukemia Leukemias are cancers of white blood cells or of cells that develop into white blood cells. White blood cells develop from stem cells in the bone marrow. Sometimes the development goes awry... read more .
Diagnosis of Myelofibrosis
Bone marrow biopsy
Anemia and the misshapen, immature red blood cells seen in blood samples viewed under a microscope, suggest myelofibrosis. However, a bone marrow biopsy Bone Marrow Examination Red blood cells, most white blood cells, and platelets are produced in the bone marrow, the soft fatty tissue inside bone cavities. Sometimes a sample of bone marrow must be examined to determine... read more is needed to confirm the diagnosis. Tests for the JAK2, CALR, and MPL gene mutations are done. Sometimes other tests are needed to distinguish whether other blood disorders such as chronic myeloid leukemia Chronic Myeloid Leukemia (CML) Chronic myeloid leukemia is a slowly progressing disease in which cells that normally would develop into the types of white blood cells called neutrophils, basophils, eosinophils, and monocytes... read more (CML) are also present.
Prognosis of Myelofibrosis
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 Polycythemia Vera Polycythemia vera is a myeloproliferative neoplasm of the blood-producing cells of the bone marrow that results in overproduction of all types of blood cells. Polycythemia vera is due to mutations... read more or essential thrombocythemia Essential Thrombocythemia Essential thrombocythemia is a myeloproliferative neoplasm in which excess platelets are produced, leading to abnormal blood clotting or bleeding. The hands and feet may burn, turn red, and... read more 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 of Myelofibrosis
Sometimes stem cell transplantation
Sometimes ruxolitinib, fedratinib, or pacritinib
Stem cell transplantation Stem Cell Transplantation Stem cell transplantation is the removal of stem cells (undifferentiated cells) from a healthy person and their injection into someone who has a serious blood disorder. (See also Overview of... read more (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. Fedratinib and pacritinib also inhibit the JAK2 mutation and can be used as alternatives 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.
Doctors sometimes also give thalidomide or lenalidomide together with prednisone, which can help maintain the platelet count and also reduce the size of the spleen.
Other drugs are being developed to treat myelofibrosis, so people may want to search for a clinical trial.
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: Primary Myelofibrosis: supports research as well as advocacy and education, including on symptoms, diagnosis, and treatment for people with primary myelofibrosis
Drugs Mentioned In This Article
|Generic Name||Select Brand Names|
|DROXIA, HYDREA, Mylocel, Siklos|
|Deltasone, Predone, RAYOS, Sterapred, Sterapred DS|