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CML is the rarest of the four major forms of leukemia. CML results from a change or mutation in the DNA of a single bone marrow cell. As a chronic leukemia, it typically progresses slowly and permits the growth of greater numbers of (immature) irregular cells. While a normal white blooleukemia. Leukemia involving the type of marrow cell that forms special white blood cells known as lymphocytes is called “lymphocytic” or “lymphoblastic” leukemia. Where the cell changes take place in a type of marrow cell that normally goes on to form red blood cells, some types of white blood cells, and platelets, the leukemia is called “myeloid.” CML is known by several other names, including chronic myelogenous leukemia, chronic myelocytic leukemia, and chronic granulocytic d cell count is in the 5,000 to 10,000 range, in CML patients the count is typically between 50,000 and 500,000 at the time of diagnosis. Left unchecked, this cell overgrowth ultimately will lead to the patient’s death.
Although most cancers have “stages,” CML has phases: chronic phase; accelerated phase; and blast crisis. Most patients, approximately 80 percent, are diagnosed in the chronic phase. As with many cancers, an early diagnosis (i.e., during the chronic phase) is important.
People with CML may not have any symptoms at the time of their diagnosis. Often the diagnosis is made in connection with a regular checkup or a medical examination for another condition. Some people with CML, however, are symptomatic. Potential symptoms may include fatigue, shortness of breath while doing everyday activities, an enlarged spleen, or being anemic.
In most cases, blood and marrow cells are examined to make a CML diagnosis. Various laboratory tests are used to examine the blood and marrow cells. With CML, the hemoglobin concentration is decreased and the white cell count is increased, often to very high levels. The number of platelets may be increased or decreased, depending on the severity of the person’s disease. Bone marrow samples are examined to confirm the blood test findings and to determine if a chromosomal abnormality known as the “Philadelphia chromosome” exists.
Nearly 30,000 people in America are living with CML and it was estimated that more than 5,100 people were diagnosed with CML in 2011. The number of people living with CML has grown dramatically since 2001 due to improved treatments. CML can strike someone at any age – even children are diagnosed with CML. But the rate of incidence increases with age, from about less than one in 100,000 people up to age 40, about two in 100,000 people at 55, to about nine in 100,000 people at 80 and older. Most diagnoses occur in people between the ages of 50 to 69.
Thanks to committed scientists and research that dates back to 1960, we understand the specific abnormality resulting in CML. The abnormal cell growth is caused by a change in the person’s chromosomes. Human cells normally have 23 pairs of chromosomes. In CML patients, sections of chromosome 9 and chromosome 22 switch places, changing both chromosomes. The altered 22 chromosome, also known as the Philadelphia chromosome, gives the CML patient’s body new instructions which result in both the over production of white blood cells and development of other immature blood cells which are incapable of full development. Left unchecked, these actions will result in the person’s death. This “translocation” of chromosome 9 and chromosome 22 is found only in the CML cells and in a portion of patients with acute lymphoblastic leukemia.
An understanding of the translocation of the chromosomes is not merely a footnote of interest to scientists. This discovery served as the foundation for effective new treatments. Prior to 2001, traditional therapies such as chemotherapy were used, and the average life expectancy after diagnosis was three to five years. Now most patients today can expect to live a normal lifespan as long as they have access to treatment and adhere to the prescribed treatment. The reason for this huge reversal in survival fortune for CML patients is a new form of targeted drug therapy that has been available to patients since 2001. This category of drugs, known as tyrosine kinase inhibitors, interferes with the signal activity that results in the proliferation of cancer cells. More specifically, these drugs target the BCR-ABL protein associated with the Philadelphia chromosome and, like many of today’s targeted therapies, leave healthy cells alone.
These treatments have transformed this previously fatal leukemia into a manageable chronic disease for most patients. The oldest of these treatments is imatinib mesylate (Gleevec), which has been the standard initial therapy for chronic phase CML since 2001. Studies have shown that Gleevec can keep the chronic phase of CML under control for at least 10 years, the length of the observation period since this drug’s approval. Not all patients succeed with this drug.
Some CML patients experience side effects of Gleevec that are significant enough to require them to discontinue the drug. In some patients the disease becomes resistant to Gleevec.
In 2010, two additional oral drug therapies – dasatinib (Sprycel) and nilotinib (Tasigna) – were approved for newly diagnosed chronic phase CML patients. Neither Sprycel nor Tasigna has been shown to result in longer survival at this point. Some findings suggest that these drugs may produce faster complete cytogenetic and molecular response, which might prove to be associated with better long-term outcomes. Additionally, these drugs provide options for some patients who cannot take Gleevec. Two additional tyrosine kinase inhibitors, bosutinib and ponatinib, are now being used in clinical trials and are expected to become available for CML patients in the future.
Those who do not respond to this type of treatment may be treated by a bone marrow or stem cell transplant, a potentially curative treatment for the disease. Older treatments are sometimes used on patients and important clinical trials are ongoing.
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