Myeloproliferative Disorders

Also Listed As: Bone Marrow Disorders; Chronic Myelogenous Leukemia; Myelofibrosis; Polycythemia Vera; Thrombocytosis

Myeloproliferative disorders are a group of conditions that cause an overproduction of blood cells – platelets, white blood cells, and red blood cells – in the bone marrow. Though myeloproliferative disorders are serious, and may pose particular health risks, individuals with these conditions often live for many years after diagnosis. Myeloproliferative disorders include:

• Polycythemia vera – overproduction of blood cells (particularly red blood cells) by the bone marrow
• Essential thrombocytosis–overproduction of the platelet cells, the cells that promote blood clotting
• Primary or idiopathic myelofibrosis (also known as myelosclerosis)–overproduction of collagen or fibrous tissue in the bone marrow; impairs bone marrow's ability to produce blood cells
• Chronic myelogenous leukemia (CML)–cancer of the bone marrow that produces abnormal granuloctyes (a type of white blood cell) in the bone marrow

Signs and Symptoms

Many individuals with myeloproliferative disorders have no symptoms at all when their physicians first make the diagnosis. A sign that is common to all myeloproliferative disorders (with the exception of essential thrombocytosis) is an enlarged spleen, which can lead to abdominal pain and a feeling of fullness.

Some signs and symptoms specific to the different types of myeloproliferative disorders include:

Polycythemia vera

• Fatigue, general malaise
• Difficulty breathing
• Intense itching after bathing in warm water
• Stomach aches
• Purple spots or patches on the skin
• Nosebleeds, gum or stomach bleeding, or blood in the urine
• Throbbing and burning pain in the skin, often with darkened, blotchy areas
• Headache and visual disturbances
• High blood pressure
• Blockage of blood vessels; may cause heart disease, stroke, or gangrene (tissue death) of the extremities

Essential thrombocytosis

• Heart attack or stoke
• Headache
• Burning or throbbing pain, redness, and swelling of the hands and feet
• Bruising
• Gastrointestinal bleeding or blood in the urine

Primary myelofibrosis

• Fatigue, general malaise
• Difficulty breathing
• Anemia
• Weight loss
• Fever and night sweats
• Abnormal bleeding

Chronic myelogenous leukemia (CML)

• Fatigue, general malaise
• Weight loss or loss of appetite
• Fever and night sweats
• Bone or joint pain
• Heart attack or stroke
• Difficulty breathing
• Gastrointestinal bleeding
• Infection

Causes

All myeloproliferative disorders arise from an overproduction of one or more types of cells. The reason for this abnormal increase in cells is largely unknown, but there are some theories as to why they occur. These include:

• Genetics – some individuals with CML have an abnormally shortened chromosome known as the Philadelphia chromosome
• Environment – some studies indicate that myeloproliferative disorders may result from an overexposure to radiation, electrical wiring, or chemicals

Risk Factors

The following risk factors may increase an individual's risk for developing a myeloproliferative disorder:

Polycythemia vera

• Gender – men are two times more likely than women to develop the condition
• Age – individuals older than 60 are most likely to develop the condition, though it may occur at any age
• Environment – exposure to intense radiation may increase an individual's risk for the condition

Essential thrombocytosis

• Gender – women are 1.5 times more likely than men to develop the condition
• Age – individuals older than 60 are most likely to develop the condition, though 20% of those with this condition are under 40.
• Environment – exposure to chemicals in hair dyes or to electrical wiring may increase an individual's risk for the condition

Primary myelofibrosis

• Gender – men are slightly more likely than women to develop the condition
• Age – individuals between the ages of 60 and 70 are most likely to develop the condition
• Environment – exposure to petrochemicals (such as benzene and toluene) and intense radiation may increase an individual's risk of developing the condition

Chronic myelogenous leukemia (CML)

• Gender – men are more likely than women to develop the condition
• Age – individuals between the ages 45 and 50 are the most likely to develop the condition
• Environment – exposure to intense radiation may increase an individual's risk of developing the condition

Diagnosis

A sign that is common to all myeloproliferative disorders (with the exception of essential thrombocytosis) is an enlarged spleen, which can be detected during a routine physical examination. In addition to performing a physical exam, the physician may also conduct the following procedures to diagnose a myeloproliferative disorder:

• Blood tests – detect abnormal types or numbers of red or white blood cells; can also detect anemia and leukemia
• Bone marrow biopsy – sample of bone marrow may be taken after blood tests; indicates the presence of abnormal types or numbers of red or white blood cells; may detect certain types of anemia and cancer in the marrow

Treatment Approach

Unfortunately, there are no known cures for most myeloproliferative disorders. There are, however, a number of treatments that help improve symptoms and prevent complications associated with the conditions.

The approach to treatment for each type of myeloproliferative disorder is slightly different:

• Polycythemia vera – lower red blood cell count by removing blood (phlebotomy)
• Essential thrombocytosis – treat symptoms, when present, with medications
• Primary myelofibrosis – treat symptoms, when present, with medications
• CML – bone marrow transplant offers the only hope for a cure; some medications (such as interferon) are used experimentally and preliminary studies suggest that vitamin A (combined with medications) may improve survival rates

Medications

An individual's diagnosis and symptoms will determine the type of medication that a physician prescribes. Some possible medications include:

Polycythemia vera

• Hydroxurea – reduces number of platelets
• Salicylates (such as aspirin) – reduces skin redness and burning, and lowers increased temperature that may occur with the condition
• Antihistamines – decreases itching
• Allupurinol – reduces symptoms of gout, a potential complication of polycythemia vera

Essential Thrombocytosis

• Aspirin – low doses may treat headache and burning pain in the skin
• Hydroxyurea – reduces the number of blood platelets
• Aminocaproic acid – reduces bleeding; may be used prior to a surgical procedure to prevent bleeding as well

Primary myelofibrosis

• Hydroxyurea – may control complications, such as enlargement of the liver and spleen, reduce the number of white cells and platelets in the blood, and improve anemia

Chronic myelogenous leukemia (CML)

• Hydroxyurea – reduces number of white blood cells
• Allopurinol – can prevent gout, a potential complication of CML
• Interferon – helps the immune system to combat cancer cells; used only if bone marrow transplant is not an option
• Chemotherapies, such as cytarabine and daunorubicin – helps the immune system to combat cancer cells; there are newer agents that are under investigation as well

Surgery and Other Procedures

In the case of primary myelofibrosis, CML, and late stage polycythemia vera, blood formation occurs in sites other than the bone marrow, such as the liver and spleen, causing enlargement of these organs. When enlargement of the spleen becomes painful, a surgeon may perform a splenectomy to remove this organ.

In very serious cases of primary myelofibrosis, surgeons may replace the abnormal stem cells (cells that manufacture blood cells) in the bone marrow with healthy stem cells. This type of procedure, called a stem cell transplant, carries a high degree of risk. Another procedure, called a bone marrow transplant, is ideal for most individuals with CML. After either type of transplant, the healthy bone marrow cells circulate and begin to grow and produce healthy blood cells.

Phlebotomy may prevent the accumulation of blood and decrease the risk of stroke in individuals with polycythemia vera.

Nutrition and Dietary Supplements

Preliminary studies suggest that nutritional supplements may reduce the symptoms of some myeloproliferative disorders. These nutritional supplements include:

Vitamin A
According to the results of a seven-year study of individuals with CML, chemotherapy combined with vitamin A may be significantly more effective than chemotherapy alone in improving an individual's chance of survival. Laboratory studies also indicate that vitamin A may inhibit tumor growth in cancer cells.

Vitamin K
Laboratory studies suggest that synthetic vitamin K inhibits the growth of CML cells and enhances the effect of the chemotherapy drug, doxorubicin. Some researchers speculate that taking vitamin K while undergoing chemotherapy with doxorubicin may increase an individual's chance of survival with minimal toxic side effects. More research is needed, however, to confirm this theory.

Herbs

Although herbs have not been scientifically investigated specifically for the treatment of myeloproliferative disorders, a trained specialist may recommend the following to improve symptoms associated with the conditions:

Frankincense (Boswellia carteri)
Laboratory studies indicate that this traditional Chinese herb, normally used for improving blood circulation and relieving pain, may inhibit the growth of cancer cells. These effects, however, have been observed only in the laboratory, and may not translate to human patients.

Other Considerations

Pregnancy
The drug hydroxyurea, when used to treat myeloproliferative disorders, may pose a risk to a developing fetus and should be avoided by pregnant women.

Prognosis and Complications

Myeloproliferative disorders are slow acting, and don't always cause life-threatening symptoms. The complications of these illnesses, however may be serious. Some complications include:

• Enlargement of the spleen and liver
• Gout
• Anemia
• Bleeding
• Kidney or liver failure
• Heart attacks or stroke
• Infection
• CML can transform into acute leukemia, a more toxic condition

The survival rate for myeloproliferative disorders varies, depending on both the type of disorder and the kind of symptoms experienced by each individual. Very serious cases, such as primary myelofibrosis, may be fatal within 3 to 6 years. Individuals with CML have a median survival rate of 4 to 5 years after diagnosis. If CML transforms into acute leukemia, however, the median survival rate is only three months. Those with other types of myeloproliferative disorders can live much longer, especially if they are diagnosed early. Individuals with primary thrombocythemia have a near normal life expectancy with only a low risk of developing cancer. Polycythemia vera has a survival rate of between 10 and 20 years, with the longest survival occurring in the younger age groups.

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