Myelofibrosis

Myelofibrosis is an uncommon type of bone marrow cancer that disrupts your body’s normal production of blood cells.

Myelofibrosis causes extensive scarring in your bone marrow, leading to severe anemia that can cause weakness and fatigue. Bone marrow scarring can also cause you to have a low number of blood-clotting cells called platelets, which increases the risk of bleeding. Myelofibrosis often causes an enlarged spleen.

Myelofibrosis is considered to be a chronic leukemia — a cancer that affects the blood-forming tissues in the body. Myelofibrosis belongs to a group of diseases called myeloproliferative disorders.

Myelofibrosis can happen on its own (primary myelofibrosis) or it can develop from another bone marrow disorder (secondary myelofibrosis).

Symptoms of Myelofibrosis

Myelofibrosis usually develops slowly. In its very early stages, many people don’t experience signs or symptoms.

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 an enlarged spleen
Easy bruising
Easy bleeding
Excessive sweating during sleep (night sweats)
Fever
Bone pain

Causes of Myelofibrosis

Myelofibrosis occurs when bone marrow stem cells develop changes (mutations) in their DNA. The stem cells have the ability to replicate and divide into the multiple specialized cells that make up your blood — red blood cells, white blood cells and platelets.

It’s not clear what causes the genetic mutations in bone marrow stem cells.

As the mutated blood stem cells replicate and divide, they pass along the mutations to the new cells. As more and more of these mutated cells are created, they begin to have serious effects on blood production.

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 and varying levels of platelets. In people with myelofibrosis, the normally spongy bone marrow becomes scarred.

Several specific gene mutations have been identified in people with myelofibrosis. The most common is the Janus kinase 2 (JAK2) gene mutation. Other less common mutations include CALR and MPL. Some people with myelofibrosis don’t have any identifiable gene mutations. Knowing whether these gene mutations are associated with your myelofibrosis helps determine your prognosis and your treatment.

Risk factors

Although the cause of myelofibrosis often isn’t known, certain factors are known to increase your risk:

Age. Myelofibrosis can affect anyone, but it’s most often diagnosed in people older than 50.
Another blood cell disorder. A small portion of people with myelofibrosis develop the condition as a complication of essential thrombocythemia or polycythemia vera.
Exposure to certain chemicals. Myelofibrosis has been linked to exposure to industrial chemicals such as toluene and benzene.
Exposure to radiation. People exposed to very high levels of radiation have an increased risk of myelofibrosis.

Diagnosis of Myelofibrosis

Tests and procedures used to diagnose myelofibrosis include:

Physical exam. Your doctor will perform a physical exam. This includes a check of vital signs, such as pulse and blood pressure, as well as checks of your lymph nodes, spleen and abdomen.
Blood tests. In myelofibrosis, a complete blood count typically shows abnormally low levels of red blood cells, a sign of anemia common in people with myelofibrosis. White blood cell and platelet counts are usually abnormal, too. Often, white blood cell levels are higher than normal, although in some people they may be normal or even lower than normal. Platelet counts may be higher or lower than normal.
Imaging tests. Imaging tests, such as X-rays and MRI, may be used to gather more information about your myelofibrosis.
Bone marrow examination. Bone marrow biopsy and aspiration can confirm a diagnosis of myelofibrosis.
In a bone marrow biopsy, a needle is used to draw a sample of bone tissue and the enclosed marrow from your hipbone. During the same procedure, another type of needle may be used to withdraw a sample of the liquid portion of your bone marrow. The samples are studied in a laboratory to determine the numbers and types of cells found.
Testing cancer cells for gene mutations. In a laboratory, doctors will analyze your blood or bone marrow cells for gene mutations, such as JAK2, CALR and MPL. Your doctor uses the information from these tests to determine your prognosis and your treatment options.

Treatment of Myelofibrosis

The goal of treatment for most people with myelofibrosis is to provide relief from signs and symptoms of the disease. For some, a bone marrow transplant may provide a chance for a cure, but this treatment is very hard on the body and it might not be an option for many people.

Low-risk myelofibrosis may not require immediate treatment, while people with high-risk myelofibrosis may consider an aggressive treatment, such as bone marrow transplant. For intermediate-risk myelofibrosis, treatment is usually directed at managing symptoms.

Immediate treatment may not be necessary

Myelofibrosis treatment may not be necessary if you aren’t experiencing symptoms. You might not need treatment right away if you don’t have an enlarged spleen and you don’t have anemia or your anemia is very mild. Rather than treatment, your doctor is likely to monitor your health closely through regular checkups and exams, watching for any signs of disease progression. Some people remain symptom-free for years.

Treatments for anemia

If myelofibrosis is causing severe anemia, you may consider treatment, such as:

Blood transfusions. If you have severe anemia, periodic blood transfusions can increase your red blood cell count and ease anemia symptoms, such as fatigue and weakness. Sometimes, medications can help improve anemia.
Androgen therapy. Taking a synthetic version of the male hormone androgen may promote red blood cell production and may improve severe anemia in some people.
Thalidomide and related medications. Thalidomide (Thalomid) and the related drug lenalidomide (Revlimid) may help improve blood cell counts and may also relieve an enlarged spleen. These drugs may be combined with steroid medications.

Treatments for an enlarged spleen

If an enlarged spleen is causing complications, your doctor may recommend treatment. Your options may include:

Targeted drug therapy. Targeted drug treatments focus on specific abnormalities present within cancer cells. Targeted treatments for myelofibrosis focus on cells with the JAK2 gene mutation. These treatments are used to reduce symptoms of an enlarged spleen.
Chemotherapy. Chemotherapy uses powerful drugs to kill cancer cells. Chemotherapy drugs may reduce the size of an enlarged spleen and relieve related symptoms, such as pain.
Surgical removal of the spleen (splenectomy). If your spleen becomes so large that it causes you pain and begins to cause harmful complications — and if you don’t respond to other forms of therapy — you may benefit from having your spleen surgically removed.
Radiation therapy. Radiation uses high-powered beams, such as X-rays and protons, to kill cancer cells. Radiation therapy can help reduce the size of the spleen when surgical removal isn’t an option.

Bone marrow transplant

A bone marrow transplant, also called a stem cell transplant, is a procedure to replace your diseased bone marrow using healthy blood stem cells. For myelofibrosis, the procedure uses stem cells from a donor (allogeneic stem cell transplant).

This treatment has the potential to cure myelofibrosis, but it also carries a high risk of life-threatening side effects, including a risk that the new stem cells will react against your body’s healthy tissues (graft-versus-host disease).

Prior to a bone marrow transplant, you receive chemotherapy or radiation therapy to destroy your diseased bone marrow. Then you receive infusions of stem cells from a compatible donor.