Tuesday, November 18, 2008

Acute Lymphocytic Leukemia (ALL)

About 3,970 new cases of acute lymphocytic leukemia (ALL) are diagnosed each year in the United States. It is the most common type of leukemia under the age of 19. Children are most likely to develop the disease, but it can occur at any age. Acute lymphocytic leukemia may be called by several names, including acute lymphoid leukemia and acute lymphoblastic leukemia.

ALL results from an acquired (not inherited) genetic injury to the DNA of a single cell in the bone marrow. The disease is often referred to as acute lymphoblastic leukemia because the leukemic cell that replaces the normal marrow is the (leukemic) lymphoblast. The effects are: 1) the uncontrolled and exaggerated growth and accumulation of cells called "lymphoblasts" or "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), platelets (thrombocytopenia), and normal white cells (especially neutrophils, i.e., neutropenia) in the blood. In most cases, the cause of acute lymphocytic leukemia is not evident. Few factors have been associated with an increased risk of developing the disease. Exposure to high doses of irradiation, as carefully studied in the Japanese survivors of atomic bomb detonations, is one such factor. Unlike other forms of leukemia, acute lymphocytic leukemia occurs at different rates in different locations. There are higher leukemia rates in more developed countries and in higher socioeconomic groups.

The current causes of acute lymphoblastic leukemia in children or adults are not known. Scientists continue to explore possible relationships with life-style or environmental factors but no firm conclusions have yet been reached. Given the amount of study, this suggests that multifaceted complex factors may be involved. It is extremely disconcerting to patients and their families to wonder what they may have done differently to avoid the disease. Unfortunately, at the present time there is no known way to prevent the disease. Acute lymphocytic leukemia occurs most often in the first decade of life but increases in frequency again in older individuals. Acute lymphocytic leukemia can develop from primitive lymphocytes that are in various stages of development.

The principal subtypes are uncovered by special tests on the leukemic lymphoblasts called "immunophenotyping." Phenotype is the physical characteristics of the cells and these are measured using immune tools. The subclassification of cell types is important since it helps to determine the best treatment to apply in each type of leukemia. The principle subtypes are T lymphocyte and B lymphocyte types, so named because the cell has features that are similar to normal T or B lymphocytes. In addition, the B cell type can be divided into a precursor B cell type, as well. Once these features are determined the term used may be acute T lymphoblastic leukemia or acute precursor (or pre) B cell lymphoblastic leukemia. Other markers on the lymphoblasts that can be detected with immunophenotyping and may be useful to the physician include the common acute lymphoblastic leukemia antigen, cALLa, now called CD 10.

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. Signs of bleeding because of a very low platelet count may be noticed. These include black-and-blue marks occurring for no reason or because of a minor injury, the appearance of pinhead-sized, red spots under the skin, called petechiae, or prolonged bleeding from minor cuts. Discomfort in the bones and joints may occur. Fever in the absence of an obvious cause is common. Leukemic lymphoblasts may accumulate in the lymphatic system, and the lymph nodes can become enlarged. The leukemia cells can also collect on the lining of the brain and spinal cord and lead to headache or vomiting.

• Medical history and physical examination
• Complete blood counts
• Bone marrow examination
• Cytogenetics
• 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 almost always shows leukemia 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 samples are used to diagnose and classify the disease. The following tests are used in the further classification of the disease. Examination of leukemic cells by cytogenetic techniques permits identification of chromosomes or gene abnormalities in the cells. The immunophenotyping 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.

A method that 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 and lymphoma, in determining treatment approaches, and in following the response to treatment.

The WBC's seen here are lymphocytes, but they are blasts--very immature cells with larger nuclei that contain nucleoli. Such lymphocytes are indicative of acute lymphocytic leukemia (ALL). ALL is more common in children than adults. Many cases of ALL in children respond well to treatment, and many are curable


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