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Myeloproliferative disorders

Also listed as: Bone marrow disorders; Chronic myelogenous leukemia; Myelofibrosis; Polycythemia vera; Thrombocytosis

• Signs and Symptoms
• Causes
• Risk Factors
• Diagnosis
• Treatment
• Other Considerations
• Supporting Research

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. This impairs bone marrow's ability to produce blood cells.
• Chronic myelogenous leukemia (CML) -- cancer of the bone marrow that produces abnormal granulocytes (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. This 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 theories 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 - 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 - 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 doctor may also conduct the following procedures to diagnose a myeloproliferative disorder:

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

Treatment

Unfortunately, there are no known cures for most myeloproliferative disorders. There are, however, several 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 doctor prescribes. Some possible medications include:

Polycythemia vera

• Hydroxyurea -- 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.
• Allopurinol -- 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. This treatment may be used prior to surgery 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 combat cancer cells. Used only if bone marrow transplant is not an option.
• Chemotherapies, such as cytarabine and daunorubicin -- helps the immune system combat cancer cells. Newer agents 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

A comprehensive treatment plan for myeloproliferative disorders may include a range of complementary and alternative therapies. Preliminary studies suggest that nutritional supplements may reduce the symptoms of some myeloproliferative disorders. Ask your team of health care providers about the best ways to incorporate these therapies into your overall treatment plan. Always tell your health care provider about the herbs and supplements you are using or considering using, as some supplements may interfere with conventional cancer treatments.

Following these nutritional tips may help reduce symptoms:

• Try to eliminate potential food allergens, including dairy, wheat (gluten), corn, preservatives, and food additives. Your health care provider may want to test for food sensitivities.
• Eat antioxidant foods, including fruits (such as blueberries, cherries, and tomatoes), and vegetables (such as squash and bell peppers).
• Avoid refined foods, such as white breads, pastas, and especially sugar.
• Eat fewer red meats and more lean meats, cold-water fish, tofu (soy, if no allergy) or beans for protein.
• Use healthy oils, such as olive oil or vegetable oil.
• Reduce or eliminate trans-fatty acids, found in commercially baked goods such as cookies, crackers, cakes, French fries, onion rings, donuts, processed foods, and margarine.
• Avoid coffee and other stimulants, alcohol, and tobacco.
• Drink 6 - 8 glasses of filtered water daily.
• Exercise at least 30 minutes daily, five days a week.

You may address nutritional deficiencies with the following supplements:

• A daily multivitamin, containing the antioxidant vitamins A, C, E, the B-complex vitamins, and trace minerals such as magnesium, calcium, zinc, and selenium.
• Omega-3 fatty acids, such as fish oil, 1 - 2 capsules or 1 - 3 tablespoonfuls oil, one to three times daily, to help decrease inflammation and help with immunity. Cold-water fish, such as salmon or halibut, are good sources, but not substitutes for supplementation.
• Grapefruit seed extract ( Citrus paradisi ), 100 mg capsule or 5 - 10 drops (in favorite beverage) three times daily when needed, for antibacterial, antifungal, and antiviral activity, and for immunity.
• N-acetyl cysteine, 200 mg daily, for antioxidant effects.
• Probiotic supplement (containing Lactobacillus acidophilus ), 5 - 10 billion CFUs (colony forming units) a day, when needed for maintenance of gastrointestinal and immune health. You should refrigerate your probiotic supplements for best results.
• Coenzyme Q10, 100 - 200 mg at bedtime, for antioxidant and immune activity.
• Melatonin, 2 - 6 mg at bedtime as needed, for immune support and sleep.

Herbs

Herbs are generally a safe way to strengthen and tone the body's systems. As with any therapy, you should work with your health care provider to get your problem diagnosed before starting any treatment. You may use herbs as dried extracts (capsules, powders, teas), glycerites (glycerine extracts), or tinctures (alcohol extracts). Unless otherwise indicated, you should make teas with 1 tsp. herb per cup of hot water. Steep covered 5 - 10 minutes for leaf or flowers, and 10 - 20 minutes for roots. Drink 2 - 4 cups per day. You may use tinctures alone or in combination as noted.

• Green tea ( Camellia sinensis ) standardized extract, 250 - 500 mg daily, for inflammation, and for antioxidant, and immune effects. Use caffeine-free products. You may also prepare teas from the leaf of this herb.
• Arabinoxylan (mushroom extract), 1,000 mg three times daily, for immune support.
• Olive leaf ( Olea europaea ) standardized extract, 250 - 500 mg one to three times daily, for anticancer and immune effects.
• Turmeric ( Curcuma longa ) standardized extract, 300 mg three times a day, for pain and inflammation.
• Milk thistle ( Silybum marianum ) seed standardized extract, 80 - 160 mg two to three times daily, for detoxification and antioxidant support.

Other Considerations

Pregnancy

Pregnant women should avoid the drug hydroxyurea, which can treat myeloproliferative disorders, because it may pose a risk to a developing fetus.

Prognosis and Complications

Myeloproliferative disorders are slow acting, and don't always cause life-threatening symptoms. The complications of these conditions, 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 - 6 years. Individuals with CML have a median survival rate of 4 - 5 years after diagnosis. If CML transforms into acute leukemia, however, the median survival rate is only 3 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 - 20 years, with the longest survival occurring in the younger age groups.

Supporting Research

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• Review Date: 10/19/2006
• Reviewed By: Ernest B. Hawkins, MS, BSPharm, RPh, Health Education Resources; and Steven D. Ehrlich, N.M.D., private practice specializing in complementary and alternative medicine, Phoenix, AZ. Review provided by VeriMed Healthcare Network.

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