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Myeloproliferative disorders

Bone marrow disorders; Chronic myelogenous leukemia; Myelofibrosis; Polycythemia vera; Thrombocytosis

Myeloproliferative disorders is the name for a group of conditions that cause blood cells, platelets, white blood cells, and red blood cells, to grow abnormally in the bone marrow. Though myeloproliferative disorders are serious, and may pose certain health risks, people with these conditions often live for many years after diagnosis. The prognosis largely depends on the type of disorder.

Myeloproliferative disorders include:

  • Polycythemia vera. Occurs when the bone marrow produces too many blood cells, especially red blood cells. More than 95% of people with polycythemia vera carry the blood mutation JAK2V617F.
  • Essential thrombocytosis. Occurs when the body produces too many platelet cells, which help blood to clot. Clots can block blood vessels leading to heart attack or stroke.
  • Primary or idiopathic myelofibrosis , also known as myelosclerosis. Occurs when the bone marrow produces too much collagen or fibrous tissue in the bone marrow. This reduces 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 people with myeloproliferative disorders have no symptoms when their doctors first make the diagnosis. One symptom shared by all myeloproliferative disorders, with the exception of essential thrombocytosis, is an enlarged spleen. An enlarged spleen can cause abdominal pain and a feeling of fullness.

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

Polycythemia vera
  • Fatigue, general malaise
  • Trouble breathing
  • Intense itching after bathing in warm water
  • Stomachaches
  • 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 problems with vision
  • High blood pressure
  • Blockage of blood vessels. This may cause heart disease, stroke, or gangrene (tissue death) of the arms and legs.
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
  • Trouble 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
  • Trouble breathing
  • Gastrointestinal bleeding
  • Infection

Causes

All myeloproliferative disorders are caused by overproduction of one or more types of cells. No one knows what triggers the overproduction of cells, but theories include:

  • Genetics. Some people with CML have an abnormally shortened chromosome known as the Philadelphia chromosome.
  • Environment. Some studies suggest that myeloproliferative disorders may result from an overexposure to radiation, electrical wiring, or chemicals.

Risk Factors

These factors may increase your risk for developing a myeloproliferative disorder:

Polycythemia vera
  • Gender. Men are 2 times more likely than women to develop the condition.
  • Age. People older than 60 are most likely to develop the condition, though it may happen at any age.
  • Environment. Exposure to intense radiation may increase the risk for the condition.
Essential thrombocytosis
  • Gender. Women are 1.5 times more likely than men to develop the condition.
  • Age. People older than 60 are most likely to develop the condition, though 20% of those with this condition are under 40.
  • Environment. Some researchers suggest that exposure to chemicals or to electrical wiring may increase a person's risk for the condition.
Primary myelofibrosis
  • Gender. Men are slightly more likely than women to develop the condition.
  • Age. People ages 60 to 70 are most likely to develop the condition.
  • Environment. Exposure to petrochemicals, such as benzene and toluene, and intense radiation may increase the risk of developing the condition.
Chronic myelogenous leukemia (CML)
  • Gender. Men are more likely than women to develop the condition.
  • Age. People ages 45 to 50 are the most likely to develop the condition.
  • Environment. Exposure to intense radiation may increase the risk of developing the condition.

Diagnosis

A sign shared by all myeloproliferative disorders, with the exception of essential thrombocytosis, is an enlarged spleen. Your doctor may detect an enlarged spleen during a routine physical examination. In addition to doing a physical exam, the doctor may also conduct the following tests:

  • Blood tests. To find abnormal types or numbers of red or white blood cells. They can also detect anemia and leukemia.
  • Bone marrow biopsy. Your doctor may take a sample of bone marrow after blood tests. It can show 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.
  • Cytogenetic analysis. Your doctor may view blood or bone marrow are viewed under a microscope to look for changes in the chromosomes.

Treatment

There is no cure for most myeloproliferative disorders. There are, however, several treatments that help improve symptoms and prevent complications associated with the conditions.

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

  • Polycythemia vera. Lower red blood cell count by removing blood, called phlebotomy. Treatment with medication, called myelosuppressive therapy, is also available.
  • Essential thrombocytosis. Treat symptoms, when present, with medications.
  • Primary myelofibrosis. Treat symptoms, when present, with medications and blood transfusion.
  • CML. Treatment options for CML have expanded greatly and may include: targeted therapy, chemotherapy, biologic therapy, high-dose chemotherapy with stem cell transplant, donor lymphocyte infusion (DLI), surgery.

Medications

A person's diagnosis and symptoms will determine the type of medication prescribed. Some possible medications include:

Polycythemia vera

  • Hydroxyurea (Droxia, Hydrea) or anagrelide (Agrylin). Reduces number of blood cells.
  • Low-dose 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

  • Low-dose aspirin. May treat headache and burning pain in the skin.
  • Hydroxyurea (Droxia, Hydrea) or anagrelide (Agrylin) reduces number of blood cells.
  • Aminocaproic acid. Reduces bleeding. This treatment may be used before 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.
  • Thalidomide and lenalidomide. To reduce symptoms and treat anemia.

Chronic myelogenous leukemia (CML)

  • Targeted drugs. Affect a specific protein that lets cancer cells multiply. These drugs include Dasatinib (Sprycel), Imatinib (Gleevec), and Nilotinib (Tasigna).
  • Interferon. Helps the immune system combat cancer cells. Used only if bone marrow transplant is not an option.
  • Chemotherapy. Drugs such as cyclophosamide and cytarabine are often combined with other treatments to kill cancer cells.

Recently, preliminary studies have suggested that two agents, imitinib and dasatinib, are effective treatments for CML.

Surgery and Other Procedures

With primary myelofibrosis, CML, and late stage polycythemia vera, blood cells are produced in sites other than the bone marrow, such as the liver and spleen. That causes these organs to get bigger. When enlargement of the spleen becomes painful, the person may have surgery to remove it.

In very serious cases of primary myelofibrosis, the person may undergo a stem cell transplant. In this procedure, abnormal stem cells (cells that manufacture blood cells) in the bone marrow are replaced with healthy stem cells. A stem cell transplant has life-threatening risks, however. In one study, 5-year survival was 62% in people younger than 45 years and 14% in those that were older.

For people with CML, a bone marrow transplant may be an option. After either a stem cell or bone marrow transplant, the healthy bone marrow cells begin to grow and produce healthy blood cells.

Phlebotomy, removing some blood from the body, may lower the risk of stroke in people with polycythemia vera. It is the primary therapy in polycythemia vera, and it's the only treatment that has improved survival. People with anemia may need blood transfusions. In one study, researchers suggest that low dose aspirin (81 to 325 mg/day) may lower the risk of blood clots in people with polycythemia vera.

Nutrition and Dietary Supplements

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

Myeloproliferative disorders need conventional medical treatment. There are not any supplements that can specifically help with these conditions. However, following a healthy diet and getting regular exercise may help to keep your body strong while coping with a myeloproliferative disorder. Try these tips:

  • 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 caffeine, alcohol, and tobacco.
  • Drink 6 to 8 glasses of filtered water daily.
  • Exercise at least 30 minutes daily, 5 days a week.

Ask your doctor if you would benefit from 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 to 2 capsules or 1 to 3 tablespoonfuls oil, 1 to 3 times daily, to help decrease inflammation and help with immunity. Cold-water fish, such as salmon or halibut, are good sources, but you may need to take supplements to get enough omega-3 fatty acids. If you are taking aspirin or other blood thinners, such as warfarin (Coumadin) or clopidogrel (Plavix), talk to your doctor. Omega-3 fatty acids may increase bleeding.
  • Probiotic supplement (containing Lactobacillus acidophilus ) , 5 to 10 billion CFUs (colony forming units) a day, when needed for maintenance of gastrointestinal and immune health. Refrigerate your probiotic supplements for best results. People with weakened immune systems or those who take drugs to suppress the immune system should ask their doctor before taking probiotics.

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 diagnose your problem before starting treatment. You may use herbs as dried extracts (capsules, powders, or teas), glycerites (glycerine extracts), or tinctures (alcohol extracts). Unless otherwise indicated, make teas with 1 tsp. herb per cup of hot water. Steep covered 5 to 10 minutes for leaf or flowers, and 10 to 20 minutes for roots. Drink 2 to 4 cups per day. You may use tinctures alone or in combination as noted.

If you are undergoing treatment for cancer, you should always ask your doctor before taking any herbs or supplements. No herbs have been studied specifically for myeloproliferative disorders, but the following herbs may help your general health:

  • Indirubin ( Indigofera tinctoria ). In case reports, indirubin showed positive results in treating CML long-term. However, no scientific studies have been done on using indirubin for CML. Indirubin is from the indigo plant and is included in a traditional Chinese herb formula that has been used historically to treat CML. Not much is known about the safety of indirubin. Ask your doctor before taking it and only use under the guidance of a knowledgeable prescriber.
  • Olive leaf ( Olea europaea ). For anticancer and immune effects. People with diabetes and high blood pressure should ask their doctor before taking olive leaf.
  • Turmeric ( Curcuma longa ). For pain and inflammation. DO NOT use turmeric if you have gallbladder problems. Turmeric may increase the risk of bleeding, especially if you take blood thinners, such as warfarin (Coumadin), clopidogrel (Plavix), or aspirin.

Other Considerations

Pregnancy

Pregnant women should avoid the drug hydroxyurea because it may pose a risk to the baby.

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 dangerous condition.

The survival rate for myeloproliferative disorders varies, depending on both the type of disorder and the kind of symptoms each person experiences.

Supporting Research

Abraham S, Salama M, Hancock J, Jacobsen J, Fluchel M. Congenital and childhood myeloproliferative disorders with eosinophilia responsive to imatinib. Pediatr Blood Cancer . 2012;59(5):928-9.

Bauer JD, Capra S. Nutrition intervention improves outcomes in patients with cancer cachexia receiving chemotherapy -- a pilot study. Support Care Cancer . 2005;13(4):270-4.

Bell DR, Gochenaur K. Direct vasoactive and vasoprotective properties of anthocyanin-rich extracts. J Appl Physiol . 2006;100(4):1164-70.

Bruchova H, Merkerova M, Prchal JT. Aberrant expression of microRNA in polycythemia vera. Haematologica . 2008;93(7):1009-16.

Cabrera C, Artacho R, Gimenez R. Beneficial effects of green tea--a review. J Am Coll Nutr . 2006;25(2):79-99.

Chen F, Li L, Ma D, et al. Imatinib achieved complete cytogenetic response in a CML patient received 32-year indirubin and its derivative treatment. Leuk Res . 2010 Feb;34(2):e75-7.

de Lacerda JF, Oliveira SN, Ferro JM. Chronic myeloproliferative diseases. Handb Clin Neurol . 2014;120:1073-81.

De Stefano V, et al. Recurrent thrombosis in patients with polycythemia vera and essential thrombocythemia: incidence, risk factors, and effect of treatments. Haematologica . 2008;93(3):372-80.

Doron S, Gorbach SL. Probiotics: their role in the treatment and prevention of disease. Expert Rev Anti Infect Ther . 2006;4(2):261-75.

Finazzi G, Barbui T. Evidence and expertise in the management of polycythemia vera and essential thrombocythemia. Leukemia . 2008;22(8):1494-502.

Fontani G, Corradeschi F, Felici A, et al. Cognitive and physiological effects of Omega-3 polyunsaturated fatty acid supplementation in healthy subjects. Eur J Clin Invest . 2005;35(11):691-9.

Giovanni B, Michelle E, Letizia C, et al. Thalidomide in myelofibrosis with myeloid metaplasia: a pooled-analysis of individual patient data from five studies. Leuk Lymphoma . 2002;43(12):2301-7.

Goldman L, Ausiello DA, et al, eds. Cecil Textbook of Medicine . 23st ed. Vol 1. Philadelphia, PA: W.B. Saunders Company; 2007.

Kimura K, Ozeki M, Juneja LR, Ohira H. l-Theanine reduces psychological and physiological stress responses. Biol Psychol . 2006 Aug 21.

Marchetti M, Barosi G, Balestri F, et al. Low-dose thalidomide ameliorates cytopenias and splenomegaly in myelofibrosis with myeloid metaplasia: a phase II trial. J Clin Oncol . 2004;22(3):424-31.

Rotsein OD. Oxidants and antioxidant therapy. Crit Care Clin . 2001;17(1):239-47.

Tefferi A. Abeloff: Abeloff's Clinical Oncology . 4th ed. Philadelphia, PA: Elsevier Churchill Livingstone; 2008:106.

Tefferi A. Myelofibrosis with myeloid metaplasia. Med Prog . 2000;342(17):1255-65.

Tefferi A, Cortes J, Verstovsek S, et al. Lenalidomide therapy in myelofibrosis with myeloid metaplasia. Blood . 2006;108(4):1158-64.

Wang HK. The therapeutic potential of flavonoids. Expert Opin Investig Drugs . 2000;9(9):2103-19.

Xiao Z, Hao Y, Liu B, Qian L. Indirubin and meisoindigo in the treatment of chronic myelogenous leukemia in China. Leuk.Lymphoma . 2002;43:1763-8.

Yoon JH, Baek SJ. Molecular targets of dietary polyphenols with anti-inflammatory properties. Yonsei Med J . 2005;46(5):585-96.

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          Review Date: 2/2/2016  

          Reviewed By: Steven D. Ehrlich, NMD, Solutions Acupuncture, a private practice specializing in complementary and alternative medicine, Phoenix, AZ. Review provided by VeriMed Healthcare Network.

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