CML: New Molecular Test May Identify Time to Progression to Acute Disease

Chronic Myelogenous Leukemia: New Molecular Test May Identify Time to Progression to Acute Disease

Chronic myelogenous leukemia (CML) is a cancer that progresses slowly, sometimes allowing several months or even several years without symptoms. Eventually, the disease does progress to an acute phase, at which time it advances much more quickly. Now, researchers in England report that a close look at a genetic abnormality (called the Philadelphia chromosome), present in most CML cells, can help predict how long the chronic phase of disease will last and when the acute phase is likely to begin.

Chronic myelogenous leukemia, also called chronic granulocytic leukemia, is a type of cancer characterized by the presence of too many immature white blood cells, or immature granulocytes, in the blood and bone marrow. The bone marrow is the part of the body in which blood cells are produced. Young blood cells, called stem cells, develop and mature in the bone marrow into the 3 types of blood cells: white blood cells (including granulocytes), red blood cells, and platelets. In the case of CML, large numbers of young granulocytes do not mature, collect in the marrow and blood, and cannot perform their function in the body properly. Many treatment options are available to help control CML, including chemotherapy, radiation therapy, and biologic therapy (also called immunotherapy) to help the immune system. However, at this time, the use of high-dose chemotherapy (with or without radiation therapy) to kill more cancer cells, followed by a stem cell transplantation (SCT), is the only curative option for persons with CML.

Although the use of high-dose chemotherapy followed by SCT is the only option for cure, it is also associated with more side effects than chemotherapy and/or interferon. Therefore, persons often opt to receive chemotherapy and/or interferon, hoping to prolong the chronic phase of disease and increase their survival time. If doctors could tell individual patients with CML how long the chronic phase of their disease is likely to be, this could help them make more informed decisions about when to receive the SCT procedure.

Researchers in England evaluated 56 persons with CML. They examined the genetic Philadelphia chromosome defect, characterized by a switch of chromosomes 9 and 22, in the leukemia cells. This switch of chromosomes 9 and 22 is called a translocation 9:22, or t(9:22). Using a new sensitive test, called a microsatellite polymerase chain reaction (PCR), these researchers discovered that some persons with CML had molecular abnormalities in addition to the t(9:22). Furthermore, patients who had these additional molecular abnormalities had an average survival time of only 36 months, compared with more than 90 months for those who did not have these additional abnormalities.

These findings indicate that persons having the additional molecular abnormalities detected with this PCR test progress more quickly to the acute phase of disease. Persons in whom these additional defects are detected at diagnosis may wish to talk with their doctors about the risks and benefits of undergoing high-dose chemotherapy followed by a stem cell transplantation as their initial treatment. (Blood, Vol 95, No 3, pp 738-743, 2000)

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