Myeloproliferative disorders

ALSO KNOWN AS: Blood cancers, chronic granulocytic leukemia, chronic myeloid leukemia, agnogenic myeloid metaplasia, primary myelofibrosis, myelosclerosis with myeloid metaplasia, idiopathic myelofibrosis, essential thrombocytosis

RELATED CONDITIONS: Leukemia

DEFINITION: Myeloproliferative disorders are a group of slow-growing blood cancers in which the bone marrow produces too many red blood cells, white blood cells, or platelets. All myeloproliferative disorders arise from an overproduction of one or more types of blood cells.

Risk factors: The reason for the abnormal increase in blood cells is not well understood. Genetics and environmental factors such as overexposure to radiation may be risk factors for some of these malignancies. One of the most common mutations is in the JAK2 gene. This mutation appears with the same frequency in isolated cases and familiar clusters, suggesting its development is secondary to an inherited genetic predisposition.

Etiology and the disease process: No obvious etiology exists for myeloproliferative disorders, but the presence of a genetic mutation in the JAK2 gene increases an individual's risk. These malignancies begin in the bone marrow when a greater-than-normal number of stem cells develop into one or more types of blood cells. Normally, the bone marrow makes stem cells that develop into mature blood cells. There are three types of mature blood cells—red blood cells, which carry oxygen and other materials to all body tissues; white blood cells, which fight infection and disease; and platelets, which help prevent bleeding by causing blood to clot. The type of myeloproliferative disorder determines which kinds of mature blood cells are overproduced. Usually, one type of blood cell is affected more than the others. The disorders get worse as the number of blood cells increases. There are six types of chronic myeloproliferative disorders:

• Chronic myelogenous leukemia is a slowly progressing disease caused by the overproduction of white blood cells but not lymphocytes in the bone marrow. It is also known as chronic granulocytic leukemia and chronic myeloid leukemia.
• Polycythemia vera is a disease in which too many red blood cells are produced in the bone marrow and blood, causing the blood to thicken. The number of white blood cells and platelets may also increase. The spleen is often enlarged. Patients with polycythemia vera may have bleeding problems and are at high risk for blood clotting.
• Primary myelofibrosis (sometimes called chronic idiopathic myelofibrosis) is a progressive, chronic disease in which the bone marrow is replaced by fibrous tissue, and blood is produced in the liver and the spleen instead. The hallmark of this disease is an enlarged spleen. Primary myelofibrosis causes progressive anemia and is also called agnogenic myeloid metaplasia, chronic idiopathic myelofibrosis, myelosclerosis with myeloid metaplasia, and idiopathic myelofibrosis.
• Essential thrombocythemia is an increased number of thrombocytes (platelets) in the blood. The cause of this malignancy is not known. It is also called essential thrombocytosis.
• Chronic neutrophilic leukemia is a disease in which neutrophils, a type of white blood cell, are found in excess in the blood. The excess neutrophils in chronic neutrophilic leukemia may cause the spleen and liver to become enlarged. This disorder may not progress for years, or it may develop quickly into acute leukemia.
• Chronic eosinophilic leukemia is a disease in which eosinophils, a type of white blood cell, are found in the tissues, bone marrow, and blood. Similar to chronic neutrophilic leukemia, chronic eosinophilic leukemia may stay the same for years or develop quickly into acute leukemia.

Incidence: Myeloproliferative disorders typically occur later in life. The incidence of these diseases is low, ranging from approximately 0.8 to 5.1 new cases per 100,000 people each year, and they occur most commonly in men and women of Eastern European Jewish ancestry. Men are more likely than women to develop polycythemia vera, primary myelofibrosis, and CML, while women are 1.5 times more likely than men to develop essential thrombocytosis. Most individuals are diagnosed between ages sixty-five and seventy-five.

Symptoms: Many individuals with myeloproliferative disorders have no symptoms when their physicians first make the diagnosis. However, as the hematocrit or platelet count increases, most patients develop symptoms including headache, blurred vision, plethora (excess body fluid), elevated white blood cell count, and hematocrit. A sign common to all myeloproliferative disorders, aside from essential thrombocytosis, is an enlarged spleen, which may cause abdominal pain. Other signs of myeloproliferative disorders often include fatigue, difficulty breathing, intense itching after bathing in warm water, stomach aches, purple spots or patches on the skin, nosebleeds, gum or stomach bleeding, blood in the urine, throbbing and burning pain in the skin, high blood pressure, and blockage of blood vessels. Blockage of blood vessels may cause heart disease, stroke, or tissue death of the extremities.

As the disorders progess, patients may also develop cerebrovascular events, such as thrombosis. Thrombosis in small blood vessels may lead to serious events, such as cyanosis, erythromelalgia (painful vessel dilation in the extremities), ulceration, or gangrene (tissue death) in the fingers or toes. Thrombosis in larger vessels may lead to myocardial infarction, deep-vein thrombosis, transient ischemic attacks, and stroke.

Screening and diagnosis: Primary care physicians sometimes discover myeloproliferative disorders during routine blood tests. There is no standard staging system for chronic myeloproliferative disorders. Complete blood count is necessary for proper diagnosis, which includes the number of red blood cells and platelets, the number and type of white blood cells, the amount of hemoglobin (the protein that carries oxygen) in the red blood cells, and what portion of the blood sample is red blood cells. Bone marrow aspiration and biopsy are used to look for signs of blood cancer. In addition, cytogenetic analysis is often done to look for certain chromosome changes.

Treatment and therapy: There are no known cures for most myeloproliferative disorders. However, available treatments help alleviate symptoms and prevent complications associated with the disorders. The method used to alleviate symptoms depends on the type of myeloproliferative disorder. For polycythemia vera, phlebotomy (removal of blood from the body) lowers red blood cell count. In essential thrombocytosis and primary myelofibrosis, medications help improve symptoms. Medications such as interferon may also improve the survival rates of certain myeloproliferative disorders.

When spleen enlargement becomes painful, a surgeon may perform a splenectomy to alleviate the pain. Replacing the abnormal stem cells in the bone marrow with healthy stem cells may also help control the disorder. Bone marrow transplant is ideal for most patients with CML.

Prognosis, prevention, and outcomes: Though myeloproliferative disorders are serious, they are most often slow to develop; therefore, patients with these conditions often live for many years after diagnosis. Some complications of myeloproliferative disorders include enlargement of the spleen and liver, gout, anemia, bleeding, kidney or liver failure, heart attacks or stroke, and infection. In particular, CML can transform into acute leukemia.

The survival rates of those with myeloproliferative disorders depend on the type of disorder and symptoms. For example, the median survival rate for those with polycythemia vera is more than ten years with treatment. The major causes of death in untreated polycythemia vera patients are thrombosis and hemorrhage. Primary myelofibrosis and CML may be fatal within three to six years after diagnosis. However, if CML transforms into acute leukemia, the median survival rate may be only three months. Patients with other types of myeloproliferative disorders can live longer, especially when diagnosed early. Specifically, patients with primary thrombocythemia may have a normal life expectancy, and patients with polycythemia vera have a survival rate of between ten and twenty years.

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