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Traditional method of detecting leukemia cells and "clinical remission"

Leukemia was first defined in the mid-1800s as a disease distinguished by a large number of white blood cells in the blood stream. By the late-1800s, scientists were able to examine blood cells under a microscope. Later they could identify different types of white blood cells, thanks in part to staining techniques developed by Paul Ehrlich. Leukemia was further classified as "myeloid" and "lymphoblastic" according to the cell types around this time. By the mid-1900s, although the microscopes and staining methods were better, the presence of leukemia in the blood stream and bone marrow was still monitored by manual cell counts as viewed under a microscope.(4)

Today, the study of the cells' morphology under a microscope is still the "gold standard" in leukemia diagnosis and monitoring. An expert carefully studies the morphology of a slide of cells under a microscope and monitors the number of "blasts".(An excellent overview of some of the stains and methods used in examining cells under a microscope is found on University of Washington, Department of Laboratory Medicine website.) This method of monitoring cells can of detect 1 leukemia cell in 100 cells: this is called a sensitivity of 10-2.

If there are less than 5% blasts in a bone marrow sample, the patient is in "clinical remission". This term came into use in the 1950s, when this level of sensitivity was the limit of the doctors’ tests. In the words of Alec Morley in an editorial in the New England Journal of Medicine, "At this point, the patient is judged to be in clinical and hematologic remission, although the term "remission," much loved by hematologists and patients, refers only to a somewhat arbitrary point toward one end of a continuum of leukemic-cell numbers."(5)

Although doctors now know that clinical remission does not mean that the disease is eliminated, the term still has value as a prognostic factor in treatment. For example, careful studies have determined that patients that do not go into clinical remission by day 14 of treatment are at higher risk for relapse, and therefore these patients, called "slow early responders", enter on a more intense treatment regimen. Rapid early responders are able to complete a less intense treatment protocol, lessening the risks of side effects inherent in chemotherapy.

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