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List of All Topics
Myelofibrosis
Introduction
Myelofibrosis is a serious bone marrow disorder that disrupts your body's normal production of blood cells. Why these changes occur is unknown, but the result is extensive scarring in your bone marrow. This in turn leads to severe anemia — causing weakness and fatigue — and enlargement of your spleen and liver, hallmark characteristics of the disease. You may also hear myelofibrosis referred to as agnogenic myeloid metaplasia or idiopathic myelofibrosis.
An uncommon disease, myelofibrosis can occur at any age, although it most frequently develops after age 50. There's no known way to prevent myelofibrosis, and risk factors for it are unclear.
In most cases, myelofibrosis gets progressively worse. Treatment generally focuses on relieving signs and symptoms and may include medications, blood transfusions, chemotherapy, radiation therapy and surgery.
Signs and symptoms
Myelofibrosis usually develops slowly. In its very early stages, many people don't experience any signs or symptoms. But as disruption of normal blood cell production increases, signs and symptoms may include:
- Feeling tired, weak or short of breath, usually because of anemia.
- Pain or fullness below your ribs on the left side, due to enlarged spleen.
- Enlarged liver.
- Pale skin.
- Easy bruising.
- Easy bleeding.
- Excessive sweating during sleep (night sweats).
- Fever.
- Frequent infections.
- Bone pain.
The process of producing blood cells in your body is called hematopoiesis. This process starts in your bone marrow with a certain type of cell called a hematopoietic stem cell. A stem cell is a primitive, undifferentiated cell that has the ability to replicate itself and then divide into multiple specialized cells.
A hematopoietic stem cell has the ability to produce your three basic blood cells — red blood cells, white blood cells and platelets. These cells eventually wind up in the blood that circulates through your body, and each type of blood cell has an important role:
- The biggest job of red blood cells is to carry oxygen to your body's tissues and organs.
- White blood cells form an important part of your immune system and help fight infection.
- Platelets repair injured blood vessels and stop bleeding by clumping together and forming blood clots (thrombi).
How myelofibrosis occurs
Myelofibrosis develops when the genetic material in a single hematopoietic stem cell changes, or mutates. What causes this mutation is unknown, but it usually occurs during a person's lifetime rather than during the fetal development stage. In other words, it's an acquired mutation rather than one present at birth (congenital).
When the affected cell replicates itself and divides, it passes along the mutation to the new cells. As more and more of these mutated cells are created, they begin to have serious effects on the blood production process. The end result is usually a lack of red blood cells — which causes the anemia characteristic of myelofibrosis— and an overabundance of white blood cells with varying levels of platelets.
Because of the overproduction of white blood cells, doctors refer to myelofibrosis as a myeloproliferative disease, a type of disease characterized by uncontrolled production of one or more types of blood cells. Scarring (fibrosis) within the bone marrow is thought to be a secondary reaction to the activity of the mutated cells.
Your spleen and sometimes your liver may become enlarged by trapping excess white blood cells circulating through your body.
Treatment
Treatment usually focuses on managing the signs and symptoms of myelofibrosis and improving quality of life. As long as you aren't experiencing any symptoms and you don't show signs of anemia, painful spleen enlargement or other complications, treatment may not be necessary. Your doctor may simply monitor your health closely through regular checkups and exams, watching for any signs of disease progression. Some people remain symptom-free for years.
Treatment options typically include:
- Blood transfusions. If you have severe anemia, periodic blood transfusions can increase your red blood cell count and ease anemia symptoms, such as tiredness and weakness. Regular transfusions can be cumbersome, however, and other medications may help improve anemia so that you don't need blood transfusions.
- Androgen therapy. Taking a synthetic version of the male hormone androgen combined with a corticosteroid medication, such as prednisone, can promote red blood cell production and may improve severe anemia in some people. It may also reduce the need for blood transfusions. People who respond to this treatment after a month of therapy may continue on with the androgen and slowly taper off the prednisone. Androgen therapy does have certain risks, including damage to your liver and masculinizing effects in women. Men are screened for prostate cancer before starting on androgen therapy and regularly while on therapy, as androgen hormones may fuel growth of prostate cancer cells.
- Chemotherapy. Hydroxyurea (Hydrea) is the most commonly used chemotherapy drug in treating myelofibrosis. Hydroxyurea can reduce the size of an enlarged spleen, decrease high platelet counts, improve night sweats and weight loss, and possibly reduce bone marrow fibrosis.
- Radiation therapy. Radiation may relieve associated signs and symptoms, such as spinal cord compression and bone pain. It can also help reduce the size of the spleen, when surgical removal isn't an option.
- Thalidomide with steroids. Using thalidomide along with prednisone can help reduce spleen size, improve anemia and white blood cell and platelet counts, and improve other systemic symptoms, such as weakness, fatigue, night sweats and shortness of breath. This therapy can also reduce the need for blood transfusions, but it's still fairly experimental.
- Surgical removal of the spleen (splenectomy). If the size of your spleen becomes painful, begins to cause harmful complications and doesn't respond to other forms of therapy, you may benefit from having your spleen surgically removed. There are significant risks associated with this procedure, however, and you'll want to discuss this option carefully with your doctor. Risks include infection, excessive bleeding, blood clot formation leading to stroke or pulmonary embolism, and a higher rate of conversion to acute leukemia. After the procedure, some people experience liver enlargement and an abnormal increase in platelet count.
- Stem cell transplantation. In a small number of people, allogeneic stem cell transplantation — stem cell transplantation from a suitable donor — may induce long-lasting complete remissions. It may also help reverse bone marrow fibrosis. This is the only treatment that has the potential to cure myelofibrosis.
But it also has a high risk of life-threatening side effects, as it requires high doses of chemotherapy and radiation before transplantation to destroy the diseased cells and make way for the new donor cells. After the procedure, there's a risk that the new stem cells will react against your body's healthy tissues, causing potentially fatal damage (graft-versus-host disease). Other risks include organ or blood vessel damage, cataracts, and the development of a different cancer later on. Most people with myelofibrosis, because of age, stability of the disease or other health problems, don't qualify for this treatment.
Another potentially curative transplant treatment being investigated is a reduced-intensity transplant, also called a nonmyeloablative transplant or mini-transplant. People can participate in this treatment through clinical trials. The treatment involves administering lower doses of pre-transplant chemotherapy and radiation than does the standard pre-transplant regimen, followed by an infusion of healthy blood stem cells from a matched (related or unrelated) donor. This approach relies on the donor's immune cells, rather than on chemotherapy or radiation, to destroy diseased cells. While reduced-intensity transplantation still has side effects, doctors hope that it will be safer but still as effective as the more aggressive, standard transplantation.
Information obtained from National Institute of Health