Description, Causes and Risk Factors:
Alternative Name: Myelosclerosis, osteomyelofibrotic syndrome.
Myelofibrosis is an incurable bone marrow disorder that disrupts the body's normal production of blood cells. It is classed as a blood cancer, a form of chronic leukemia. The result is extensive scarring in the bone marrow, leading to severe anaemia, weakness, fatigue, and often, an enlarged spleen and liver. Myelofibrosis is also called agnogenic myeloid metaplasia or idiopathic myelofibrosis and it can occur at any age, although it tends to occur after 50 years of age.
Annual incidences are approximately 0.4 cases per 100,000. The median age at diagnosis is 60 years, and more than 90% of patients are diagnosed after age 40 years. However myelofibrosis has been reported in all age groups.
Myelofibrosis occurs when a genetic mutation occurs in blood stem cells. Blood 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 is not clear what causes the genetic mutation in blood stem cells. As the mutated blood stem cells replicate and divide, they pass along the mutation 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 with varying levels of platelets. In people with myelofibrosis, the normally spongy bone marrow becomes scarred.
The gene mutation that occurs in most people affected by myelofibrosis is sometimes referred to as JAK2. Other gene mutations also may be associated with myelofibrosis.
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 high levels of radiation, such as survivors of atomic bomb attacks, have had an increased risk of myelofibrosis. Some people who received a radioactive contrast material called Thorotrast, used from the 1920s to the 1950s, have since developed myelofibrosis.
Age: Myelofibrosis can affect anyone, but it is most often diagnosed in people between the ages of 50 and 70.
Myelofibrosis usually develops slowly. In its very early stages, many people do not experience signs or symptoms. But as disruption of normal blood cell production increases, signs and symptoms may include:
Pain or fullness below your ribs on the left side, due to enlarged spleen.
Excessive sweating during sleep (night sweats).
Feeling tired, weak or short of breath, usually because of anemia.
Petechiae and ecchymosis.
Neutropenia may cause opportunistic infection, e.g. oral thrush.
Signs of portal hypertension.
Splenomegaly (may be massive).
To confirm a diagnosis of myelofibrosis, you may have imaging studies of your bones, spleen and liver, and examination of a sample of your bone marrow.
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 ultrasound, may be used to determine the size of your spleen and others, such as magnetic resonance imaging (MRI), can identify changes in your bones that indicate 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 hardened bone 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. Studying genetic components of the bone marrow cells can reveal mutations in the cells that may help to rule out other kinds of bone marrow disorders.
Gene tests: A sample of your blood or bone marrow may be analyzed in a laboratory to look for gene mutations in your blood cells that are associated with myelofibrosis.
Physical exam: Your doctor will perform a thorough physical exam. This includes a check of such vital signs as pulse and blood pressure, as well as checks of your lymph nodes, spleen and abdomen.
Other tests may include:
Urate, LFTs, Renal profile, LDH.
JAK2 mutation screen.
FISH or RT-PCR for BCR/ABL.
Bone marrow trephine biopsy.
Other relevant tests to exclude reactive myelofibrosis eg in patients with TB.
FBC + film & Haematinics.
Immediate treatment may not be necessary, if you are not experiencing symptoms and do not show signs of anemia, an enlarged spleen or other complications, treatment usually is not necessary. Instead, 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 so that you do not need blood transfusions.
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. Androgen therapy does have risks, including liver damage, masculinizing effects in women and growth of prostate cancer cells in men.
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. Thalidomide and related drugs carry a risk of serious birth defects and require special precautions. This type of treatment is being studied in clinical trials.
If an enlarged spleen is causing complications, your doctor may recommend treatment. Your options may include:
Interferon alfa is a viable alternative to hydroxyurea therapy, especially in patients under 45 years of age. Response rates of 50% have been observed, with improvement in splenomegaly and blood cell counts.
Androgens and corticosteroids: used to treat patients with severe anaemia and may improve symptoms and decrease transfusion requirements.
Thalidomide: Small studies have reported some improvement in anaemia, thrombocytopenia, and splenomegaly. Improvements were associated with significant adverse effects, resulting in high drop-out rates. Low-dose thalidomide and prednisolone in more recent studies has been better tolerated.
The combination of low-dose thalidomide and prednisone is better tolerated and more effective than thalidomide alone.
Even with aggressive chemotherapy, remissions are rare and there is no effect on the overall course of the disease.
High-dose chemotherapy: This modality combined with autologous transplantation has been shown to slow disease progression. A small study found evidence of improvement in fibrosis.
Several new drugs are being studied, including farnesyltransferase inhibitors, tyrosine kinase inhibitors and vascular endothelial growth factor inhibitors.8
Hydroxyurea has traditionally been the preferred and most commonly used agent. Moderately effective at improving splenomegaly, leukocytosis and thrombocytosis.
Surgical removal of the spleen (splenectomy): If the size of your spleen becomes painful 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. Risks include infection, excessive bleeding and blood clot formation leading to stroke or pulmonary embolism. After the procedure, some people experience liver enlargement and an abnormal increase in platelet count.
Chemotherapy: Chemotherapy drugs may reduce the size of an enlarged spleen and relieve related symptoms, such as pain.
Radiation therapy: Radiation uses high-powered beams, such as X-rays, to kill cells. Radiation therapy can help reduce the size of the spleen, when surgical removal is not an option.
Stem cells transplant: Allogeneic stem cell transplantation — stem cell transplantation from a suitable donor — is the only treatment that has the potential to cure myelofibrosis. But it also has a high risk of life-threatening side effects. Most people with myelofibrosis, because of age, stability of the disease or other health problems, do not qualify for this treatment.
Prior to a stem cell transplant, also called a bone marrow transplant, you receive very high doses of chemotherapy or radiation therapy to destroy your diseased bone marrow. Then you receive infusions of stem cells from a compatible donor. After the procedure, there is 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.
Doctors are studying a reduced-intensity transplant, also called a non-myeloablative transplant or mini-transplant. Reduced-intensity transplants use lower doses of pre-transplant chemotherapy and radiation. Although reduced-intensity transplantation has side effects, doctors hope that it will one day be a safer option for older adults.
NOTE: The above information is educational purpose. The information provided herein should not be used during any medical emergency or for the diagnosis or treatment of any medical condition.
DISCLAIMER: This information should not substitute for seeking responsible, professional medical care.
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