Chronic Myeloid Leukemia (CML)

Background of Chronic Myeloid Leukemia (CML)

Chronic myeloid leukemia (CML) is a disease in which too many immature white blood cells are made in the bone marrow. In the first stages of CML, patients show few signs of illness. In the end, however, millions of abnormal, useless white blood cells accumulate, preventing production of normal blood cells and blood-clotting platelets. Patients suffer from infections, anemia, uncontrolled bleeding and other complications that lead to death. Chronic myeloid leukemia is distinguished from other types of leukemia by the presence of a genetic abnormality in blood cells called the Philadelphia chromosome. CML may be called by several names, including chronic granulocytic, chronic myelocytic or chronic myelogenous leukemia.

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Who is at Risk for CML?

According to National Cancer Institute estimates, chronic myeloid leukemia (CML) is relatively rare, with fewer than 5,000 people diagnosed each year in the United States. Most cases of CML occur in adults; but it's very rare in children, who account for about 2 percent of CML cases. The average age at diagnosis is 66. The frequency of the disease increases with age from about one in 1 million children in the first 10 years of life to one in 100,000 people at age 50, and to one in 10,000 people at age 80. Some studies have indicated that CML could be linked to smoking, but that is uncertain. Because there are no known risk factors, there is no known way to prevent this disease.

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Hutchinson Center CML Research

Overview of Hutchinson Center CML Research

In 1998, Center researchers published results of a research study that showed that chronic myeloid leukemia (CML) patients who received a bone-marrow transplant from a tissue-type matched unrelated donor could expect about the same five-year survival rate as patients with matched related donors. Since then, center researchers have led the way in improving the treatment of CML. Our research accomplishments include:

• Pioneering the development of DNA-based techniques that have extended the use of unrelated donors in transplants for CML and other blood-related cancers. Center researchers have also shown that some subtle tissue-type mismatches between donor and recipient are well-tolerated, a finding that will help more patients find appropriate donors for transplantation.



• The recent discovery that tissue-matched stem cell transplants in which patients are first treated with targeted busulfan and cytoxan have a survival rate of approximately 85 percent. This finding created a new 'gold standard' for transplantation success.



• Development of the mini-transplant, a modified transplant procedure that relies on the cancer-fighting potential of donor immune cells. The mini-transplant, which involves only minimal doses of radiation, offers new hope to older patients and others who are medically unfit to withstand conventional transplants.



• Development of therapies that harness the power of the immune system to fight CML. These include adoptive immunotherapy, in which patients receive transfusions of cancer-fighting donor white blood cells, an array of antibody-based treatments that specifically target cancer cells and vaccine approaches that activate the immune system against cancer cells.



• Participation in clinical trials that led to the FDA approval of the "leukemia pill," Gleevec® (also known as STI-571). With greater experience using the new drug, limitations are emerging as some patients fail to respond, while others relapse. Currently, center investigators are studying the long-term effectiveness of Gleevec to determine which CML patients are best treated with the new drug versus stem-cell transplantation.



• Development of a highly specific test for detecting trace leukemia cells — the earliest warning signals of possible relapse — in patients following treatment. The test helps doctors initiate secondary treatment at this first sign of relapse.

Understanding the molecular genetics of leukemia

What are the precise meanings of remission, relapse and cure in the context of leukemia? These are not just academic questions to Dr. Jerald Radich. Working closely with his colleagues at the Hutchinson Center and other collaborators in the Southwest Oncology Group, he seeks to improve outcomes for patients with CML by developing tests that:

• Predict initial treatment response and relapse: Radich and colleagues have developed tests sensitive enough to detect one cancer cell among a million normal cells, which allows doctors to evaluate initial response to treatment or to swiftly initiate new therapy at the earliest sign of relapse.



• Track disease progression: Radich and colleagues have used a powerful tool called DNA microarrays to determine the genetic changes that take place as CML progress from its early chronic stage to later, more aggressive stages. The work will improve patient outcomes by allowing doctors to tailor each patient's treatment precisely to their disease stage.



• Identify genes that predict response to initial therapy: Cancer patients may have different gene abnormalities associated with their disease. By determining the genes that may be associated with CML and developing tests to identify which of those genes are abnormal in an individual patient, doctors will be able to provide patients with the treatments most effective for their form of the disease.

Articles Related to Chronic Myeloid Leukemia (CML)

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• Clocking cancer progression — Collaborative study with Rosetta charts molecular timeline of chronic myeloid leukemia progression, holds promise for improving patient care
  
  
• Post-transplant survival: A study of the gap between ethnic groups
  
  
• Full recovery after cell transplantation for treating leukemia or lymphoma can take 3-5 years
  
  
• The measure of remission — First-ever use of polymerase-chain-reaction analysis for drug response helps predict prognosis for leukemia patients in remission
  
  

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