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概述

Myeloproliferative disorders (MPDs) are a subset of bone marrow disorders. They are a group of four diseases characterized by an overproduction of one or more types of blood or fiber cells in the bone marrow. Bone marrow is a soft fatty tissue that is located in the center of the body's larger bones. It contains a fibrous network, a population of undifferentiated pluripotent stem cells, and a mixture of red blood cells (RBC), white blood cells (WBC), and platelets in various stages of maturity.

Normally, the body maintains a dynamic but relatively stable number of blood cells in circulation. As cells age, die, or are removed from circulation, new ones are made in the marrow to replace them. When a particular kind of blood cell is needed, some of the stem cells in the bone marrow begin to change, becoming the immature “blast” forms of whatever cell type is in short supply. These blasts mature to become white blood cells, red blood cells, or platelets. Usually only fully mature cells are released into circulation.

With an MPD, excessive production of a cell's precursor leads to an increased number of that type of mature cell and to a corresponding increase or decrease in the number of other blood cells, which may be inhibited and crowded out. This results in symptoms related to blood cell overproduction, shortages, and dysfunction throughout the body.

The four MPDs include:

  • Chronic myelogenous (myeloid, myelocytic) leukemia (CML), a disease that leads to an overproduction of myelocytes, precursor to granulocytes - white blood cells that digest and kill invading microorganisms. Often, these overproduced cells do not function normally.(For more information on this disorder, see Leukemia.)
  • Polycythemia vera, a disease in which too many red blood cell precursors and erythrocytes (red blood cells) are made in the bone marrow. When RBCs build up in the blood stream, they cause the spleen to swell and the patient to itch all over. They also make the blood thicker, which can increase the risk of inappropriate clotting. Polycythemia vera is also called primary polycythemia. A variety of other factors can cause increased red blood cell production; for instance, long-term exposure to low concentrations of oxygen. These increases in RBCs are referred to as secondary polycythemia.
  • Agnogenic myeloid metaplasia (also known as chronic idiopathic myelofibrosis and primary myelofibrosis), a disease characterized by overproduction of fiber-producing cells, leading to excess fibrous tissue in the marrow. The dense network of fiber inhibits the normal formation and maturation of RBCs and myelocytes. The red blood cells that do enter the bloodstream are often malformed, looking like teardrops instead of circles. There may be too few normal mature red blood cells to carry oxygen, causing anemia. Fiber cells may also spread to the spleen, causing it to swell.
  • Essential Thrombocythemia, characterized by an increased number of megakaryocytes, precursor to platelets (also called thrombocytes). Platelets change shape and become "sticky" during the clotting process. This characteristic allows them to plug holes in leaking blood vessels, but excess platelets and platelet clumping can make it hard for the blood to flow normally and can increase a person's risk of developing inappropriate blood clots or of having a stroke. Essential thrombocythemia must be distinguished from secondary thrombocytosis – increased numbers of platelets caused by non-marrow disorders such as iron deficiency, rheumatoid arthritis, bleeding, or removal of the spleen.

MPDs are not curable, but their slow progression can usually be controlled and their symptoms alleviated. For each, there is a slight chance that the disease will develop into an acute leukemia. If this occurs, the course of the disease will be accelerated, the symptoms will intensify, and more aggressive treatment will be required.

 

Accordion Title
骨髓增生性疾病
  • Signs and Symptoms

    The severity of an MPD varies from patient to patient. The condition may be acute and life-threatening or it may be very subtle, existing for years before being diagnosed, frequently during a routine physical. While each condition has its own set of symptoms, they also have many in common, including:

    • Weakness and fatigue
    • Weight loss
    • Enlargement of the spleen (splenomegaly) - cells accumulate in the spleen because it makes blood cells and because it filters old or abnormal cells out of the bloodstream. This causes the spleen to swell, which can cause abdominal discomfort.
    • Bleeding and bruising, due to insufficient and/or abnormal platelets
    • Night sweats
    • Bone and joint pain
    • Pallor due to anemia (when red blood cells are decreased not increased)
    • Frequent infections

    In someone with polycythemia vera, the excess number of RBCs produced increases the volume and thickness (viscosity) of the blood. This can cause symptoms such as headaches, dizziness, visual distortion, itching, and paresthesia. Sometimes the excessive RBCs may lead to complications, such as: stomach ulcers, kidney stones, venous thrombosis, stroke, and rarely to congestive heart failure.

    Myelofibrosis occurs most frequently in those over 60 years of age. It often causes no symptoms early in the course of the disease - about 1/3 of those who are diagnosed are asymptomatic. People who do have symptoms may experience fatigue, shortness of breath, and splenomegaly. Fibrous tissue eventually fills the bone marrow, reducing the production of all blood cells. Anemia may become severe with this MPD.

    Most people with essential thrombocythemia are asymptomatic, but some develop thrombosis or hemorrhage because of increased numbers of dysfunctional platelets. This may cause tingling in the hands and feet, headaches, weakness, dizziness, nosebleeds, and easy bruising.

  • Tests

    Laboratory Tests

    Complete blood count (CBC) and differential
    CBCs and differentials are the most frequently ordered tests used to help diagnose and monitor MPDs. Often ordered as part of a yearly physical exam, they are routine tests that count the number and relative proportion of each of the different types of cells in your blood stream. They give your doctor information about the size, shape, and relative maturity of the blood cells present in your blood at that moment.

    CBCs and differentials can be used to detect WBC, RBC, and platelet increases, decreases, and abnormalities. They can help determine their severity, diagnose their cause, monitor the course of a disease, and monitor the response to treatment.

    With polycythemia vera, increased RBCs, platelets, and sometimes WBCs, may be seen. With myelofibrosis, immature granulocytes and misshapen immature teardrop-shaped red blood cells are often seen, and WBC and RBC numbers are often decreased. With thrombocythemia, greatly increased numbers of platelets are seen along with abnormally large platelets, platelet clumps, and fragments of megakaryocytes.

    Irregularities in cell counts may be due to MPDs, but they may also be due to a variety of other temporary or chronic conditions. Other testing is usually done to confirm or rule out the diagnosis of an MPD.

    Bone marrow aspiration/biopsy
    If a doctor suspects a bone marrow disorder, he may order a bone marrow aspiration or biopsy to collect a small sample of marrow. When a specialist (a pathologist, oncologist, or hematologist) examines the bone and fluid from the bone marrow sample under the microscope, he can see the number, size, and shape of precursor cells (blasts), red and white blood cells, and megakaryocytes (platelet precursors). He can determine the proportions of mature and immature cells, see any overgrowth of fibrous tissue, and detect any cancer cells from cancers that may have spread to the marrow. Most bone marrow disorders can be diagnosed during this examination.

    For more detail on this test, see Bone Marrow Aspiration and Biopsy.

    Other testing that is sometimes done includes:

    ABGs (Arterial blood gases) - This test measures the amount of gases in your arterial blood and may be done when polycythemia vera is suspected. Low levels of oxygen are associated with secondary polycythemia.

    Erythropoietin is a hormone that stimulates the bone marrow to produce RBCs. With primary polycythemia, erythropoietin levels will be very low or absent, but with secondary polycythemia they will be normal or high.

    Genetic testing is sometimes used in suspected chronic myelogenous leukemia to check for the presence or absence of a Philadelphia (Ph') chromosome or a bcr-abl translocation and in suspected polycythemia vera, myelofibrosis, and essential thrombocythemia for the presence or absence of JAK2 mutations, a gene associated with marrow cell production.

    Non-Laboratory Tests
    X-rays and other imaging scans are sometimes used to look for signs of disease such as masses of cells in the chest, spleen, or liver.

  • Treatment

    MPDs are usually not preventable or curable. The goals of MPD treatment are to slow the progression of the disease and to alleviate the symptoms and complications brought on by excessive, insufficient, and dysfunctional blood cell production. With polycythemia vera, frequent phlebotomies, the removal of pints of blood, are used to decrease the number and volume of RBCs in the blood. Once RBCs have been lowered as close to normal limits as possible, the person is monitored, and occasional phlebotomies are used to keep the levels under control. Splenomegaly, the enlargement of the spleen, and itching may persist and the person may develop symptoms of iron deficiency.

    In addition to phlebotomies, hydroxyurea, a chemotherapy drug, may be given to decrease the number of cells produced. Hydroxyurea or radiation may also be used when someone has myelofibrosis to help temporarily reduce splenomegaly pain, but this may also decrease the number of WBCs, leaving the person more vulnerable to infection. If a suitable donor is available, a bone marrow transplant may offer a potential cure for myelofibrosis in some younger patients.

    Frequent blood transfusions may be necessary to address anemia, and surgical removal of the spleen may be required if it becomes too swollen (this may happen with any of the MPDs). asymptomatic patients with thrombocythemia are monitored, but they may or may not be treated - there is not general agreement on its necessity. Small doses of aspirin, which make platelets less sticky and slow clotting, may suffice, or hydroxyurea or anagrelide (an anticlotting drug) may be used to reduce the number of platelets. If platelet numbers are not responding to drug treatment rapidly enough, plateletpheresis may also be done. During this procedure, blood is withdrawn, the platelets are removed, and then the platelet-depleted blood is returned. If thrombocythemia is due to a non-marrow cause, addressing the underlying condition may return platelet levels to normal.