Sunday, October 19, 2008

Chronic Lymphocytic Leukemia (CLL)

Each year, nearly 9,730 people in the United States learn that they have chronic lymphocytic leukemia. The disease may be referred to as chronic lymphoid leukemia or as CLL. CLL results from an acquired injury to the DNA of a single cell, a lymphocyte, in the bone marrow. This injury is not present at birth. Scientists do not yet understand what produces this change in the DNA of CLL patients. The change in the cell's DNA gives the CLL cell a growth and survival advantage. The result is the uncontrolled growth of CLL cells in the marrow, leading to an increased concentration in the blood. The CLL cells that accumulate in the marrow do not impede normal blood cell production to the extent that is the case with acute lymphocytic leukemia. This important distinction from acute leukemia accounts for the less severe early course of the disease.

Chronic lymphocytic leukemia is not associated with high-dose radiation or benzene exposures, as is the case with the other three major types of leukemia. CLL is very uncommon in individuals under 45 years of age. At the time of diagnosis, about 95 percent of patients are over age 50 and the incidence of the disease increases dramatically. The risk of chronic lymphocytic leukemia becomes measurable after age 35 and increases dramatically over succeeding decades. Early in the disease, chronic lymphocytic leukemia may have little effect on a person's well-being. The symptoms of CLL usually develop gradually:

• Patients tire more easily.
• They may feel short of breath when physically active.
• They may lose weight.
• They may experience frequent infections of the skin, lungs, kidneys or other sites.

Many CLL patients say they learned they had CLL after a routine check-up. When an enlarged lymph node or an enlarged spleen is found during a physical examination, or when a routine blood test shows a higher than normal number of lymphocytes, a physican will order lab tests to get more information. Diagnosis begins with a medical history and physical examination by the physician. To complete the diagnosis, the blood and, in most cases, the marrow cells must be examined. Physicians use a number of lab tests to look at cells in blood and marrow. A test called flow cytometry is used to find out if a patient has CLL. This test is also called immunophenotyping. Flow cytometry shows if CLL is causing the high number of lymphocytes in the blood. Flow cytometry can also show if the CLL began with a B lymphocyte or a T lymphocyte. B lypmphocyte (or B-cell CLL) is most common.

Depending on the place in lymphocytic cell development in which the malignant transformation occurs, the leukemic cells may be principally B cells, T cells, or NK cells. Most patients have a B cell type of leukemia. A minority have T or NK cell types. These distinctions may be accounted for by the malignant transformation occurring after the common lymphocyte has differentiated into one of the three types of lymphocytes. The malignant event (mutation of DNA) would, therefore, occur at the point, or after, the early specialized lymphocytes were formed.

Other lab tests are done if flow cytometry shows the patient has CLL. A cytogenetic analysis looks to see if there are changes in the chromosomes of the CLL cells. (Every cell in the body has chromosomes that carry genes. Genes contain the instructions that tell each cell what to do.)FISH (fluorescence in situ hybridization) is another test that is used to check for chromosome changes. After CLL treatment begins it can be used to see if treatment is working. This is done by measuring the number of cells with abnormal chromosomes that remain after treatment.

A bone marrow biopsy is used to look at the amount and pattern of CLL cells in the marrow. In patients with more advanced CLL a bone marrow biopsy is usually done as a baseline. The results from the baseline are compared to a repeat bone marrow biopsy after treatment. This is one way to tell how the patient is doing after treatment. This test is not always done for low-risk CLL patients. Doctors also may check the blood for immunoglobulins (gamma globulins.) Immunoglobulins are proteins that help the body fight infection. CLL patients may not have enough of these proteins. With more advanced CLL, low levels of immunoglobulins may be a cause of repeated infections.

These mature lymphocytes are increased markedly in number. They are indicative of chronic lymphocytic leukemia, a disease most often seen in older adults. This disease responds poorly to treatment, but it is indolent.


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