Monday, November 17, 2008

Acute Myelogenous Leukemia (AML)

About 11,920 new cases of acute myelogenous leukemia are diagnosed each year in the United States. Acute myelogenous leukemia (AML) may be called by several names, including: acute myelocytic leukemia, acute myeloblastic leukemia, acute granulocytic leukemia or acute nonlymphocytic leukemia.

AML results from acquired (not inherited) genetic damage to the DNA of developing cells in the bone marrow. The effects are: 1) the uncontrolled, exaggerated growth and accumulation of cells called "leukemic blasts" which fail to function as normal blood cells and 2) the blockade of the production of normal marrow cells, leading to a deficiency of red cells (anemia), and platelets (thrombocytopenia) and normal white cells (especially neutrophils, i.e., neutropenia) in the blood. In most cases the cause of AML is not evident. Several factors have been associated with an increased risk of disease. These include:

• Exposure to high doses of irradiation, as carefully studied in the Japanese survivors of atomic bomb detonations
• Exposure to the chemical benzene, usually in the work place
• Exposure to chemotherapy used to treat cancers such as breast cancer, cancer of the ovary or the lymphomas. Alkylating agents and topoisosomerase inhibitors are most frequently associated with higher risk
• Therapeutic radiation, depending on the dose and setting

AML is not contagious and is not inherited. Uncommon genetic disorders such as Fanconi anemia, Schwachman-Diamond syndrome, Down syndrome and others are associated with an increased risk of AML. Older people are more likely to develop the disease. Very rarely, AML may occur in unexpectedly high frequencies in certain families. It is thought that these families transmit a susceptibility gene(s) to offspring through the germ-line. AML incidence increases dramatically among people who are over the age of 40. It is most prevalent in the sixth, seventh, eighth and ninth decades of life.

Leukemia is a malignant disease (cancer) of the bone marrow and blood. AML can occur in a variety of ways; different types of cells may be seen by the physician in blood or marrow. Since most patients have one of seven different patterns of blood cell involvement, these patterns have formed a sub classification which is shown in the table. If there are cells that are developing features of monocytes (monocytic type) or red cells (erythroleukemic), these designations are used and so forth. Even though the leukemia cells look somewhat like blood cells, the process of their formation is incomplete. Normal, healthy blood cells are insufficient in quantity.

The sub classification of the disease is important. Different types of therapy may be used and the likely course of the disease and prognosis may be different. Additional features may be important in guiding the choice of therapy, including: abnormalities of chromosomes, the cell immunophenotype, the age and the general health of the patient, and others. Most patients feel a loss of well-being. They tire more easily and may feel short of breath when physically active. They may have a pale complexion from anemia. Several signs of bleeding caused by a very low platelet count may be noticed. They include black-and-blue marks or bruises occurring for no reason or because of a minor injury, the appearance of pin-head sized spots under the skin, called petechiae, or prolonged bleeding from minor cuts. Mild fever, swollen gums, frequent minor infections like pustules or perianal sores, slow healing of cuts or discomfort in bones or joints may occur.

• Medical history and physical examination
• Complete blood counts
• Bone marrow examination
• Cytogenetic studies
• Immunophenotyping

To diagnose the disease the blood and marrow cells must be examined. In addition to low red cell and platelet counts, examination of the stained (dyed) blood cells with a light microscope will usually show the presence of leukemic blast cells. This is confirmed by examination of the marrow, which invariably shows leukemic blast cells. The blood and/or marrow cells are also used for studies of the number and shape of chromosomes (cytogenetic examination), immunophenotyping and other special studies, if required.

Blood and bone marrow aspirate are used for specific laboratory tests to diagnose and classify the disease. The following tests are used in the diagnosis of the disease. Examination of leukemic cells by cytogenetic techniques permits identification of chromosomes or gene abnormalities in the cells. The immunophenotype and chromosome abnormalities in the leukemic cells are very important guides in determining the approach to treatment and the intensity of the drug combinations to be used. This is a laboratory test that enables the physician to determine the type of disease that is present in the patient. It uses the antigens (proteins) on the cell surface and the antibodies produced by the body that match the antigen.

The method uses the reaction of antibodies with cell antigens to determine a specific type of cell in a sample of blood cells, marrow cells, or lymph node cells. The antibodies react with specific antigens on the cell. A tag is attached to an antibody so that it can be detected. The tag can be identified by the laboratory equipment used for the test. As cells carrying their array of antigens are tagged with specific antibodies they can be identified; for example, myelogenous leukemic cells can be distinguished from lymphocytic leukemic cells. Normal lymphocytes may be distinguished from leukemic lymphocytes. This method also helps to subclassify cell types, which may, in turn, help to decide on the best treatment to apply in that type of leukemia or lymphoma. The antigen on a cell is referred to as cluster of differentiation or "CD" with an associated number. For example, CD7 and 19 may be present on leukemic lymphoblasts and CD13 and 33 on leukemic myeloblasts.

Cytogenetic examination of tissue is the process of analyzing the number and shape of the chromosomes of cells. The individual, who prepares, examines and interprets the number and shape of chromosomes in cells is called a cytogeneticist. In addition to identifying chromosome alterations, the specific genes affected can be identified in some cases. These findings are very helpful in diagnosing specific types of leukemia, in determining treatment approaches and in following the response to treatment.

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