Chronic Myeloid Leukemia (CML)

What is Adult Chronic Myeloid Leukemia?

Adult Chronic myeloid or myelogenous leukemia (CML) is a type of cancer in which the bone marrow makes too many white blood cells. Although rare compared to other types of cancer such as colon, lung, prostate, or breast cancer, adult CML is diagnosed in fewer than 5,000 people each year in the United States. Most cases occur in adults, and risk increases with age. The physicians at Rocky Mountain Cancer Center (RMCC) and the Rocky Mountain Blood and Marrow Transplant Program (RMBMTP) are specialists in the care of patients with CML.

CML may be called by several names, including chronic granulocytic, chronic myelocytic, or chronic myelogenous leukemia.

CML is a disease in which too many immature white blood cells (blasts) are produced in the bone marrow. The uncontrolled growth and accumulation of these immature cells builds up, preventing the production of normal blood cells leading to a deficiency of red blood cells, blood-clotting platelets, and normal infection-fighting white blood cells. When this happens, infection, anemia, or easy bleeding may occur.

What causes CML?

CML is distinguished from other types of leukemia by the presence of a genetic abnormality in blood cells called the Philadelphia chromosome (so named because the discovery was made at the University of Pennsylvania School of Medicine in Philadelphia). The cause of CML is unknown. In a small number of patients, the cause is exposure to very high doses of radiation (most carefully studied in the Japanese survivors of the atomic bomb). A slight increase in risk also occurs in some people treated with high-dose radiation therapy for other cancers.

How is CML diagnosed?

Possible signs of adult CML, which usually develop gradually, include tiring easily and shortness of breath when physically active. Most patients feel a loss of well-being or have a pale complexion from anemia. Discomfort on the left side of the abdomen from an enlarged spleen is frequently seen in patients with CML. Patients may also experience excessive sweating, night sweats, fever, weight loss, and intolerance for warm temperatures. The disease is often discovered during a “routine” physical examination.

Doctors use tests that examine the blood and bone marrow to detect and diagnose adult CML, including:

• Physical examination and history


• Complete blood count

     
• Number of red blood cells, white blood cells, and platelets

     
• Amount of hemoglobin (protein that carries oxygen) in the red blood cells

     
• Portion of the sample made up of red blood cells


• Bone marrow aspiration and biopsy (looking for abnormal cells)


• Cytogenetic analysis to analyze the number and shape of the chromosomes of cells


• Polymerase chain reaction (PCR) or FISH testing to detect chromosome breakage

Blood and bone marrow cells usually reveal very high levels of white cells. Examination of the stained (dyed) blood cells under a light microscope shows a small proportion of immature cells (leukemic blast cells) and a larger proportion of maturing and fully matured white cells (myelocytes and neutrophils). A sample of marrow is examined to confirm the blood findings and to determine if there is an abnormality in the chromosomes. The presence of the Philadelphia chromosome (a shortened chromosome number 22) in the marrow cells, high white blood cell counts, and other characteristic blood and marrow findings confirm the diagnosis of CML.

After CML has been diagnosed, further tests determine the phase of the cancer. A doctor might use the following procedures to find out the phase: cytogenetic analysis (looking for changes in chromosomes in the blood) or bone marrow aspiration and biopsy.

There is no standard staging system for CML—it is classified by phase instead: chronic phase, accelerated phase, or blastic phase. The plan of treatment is determined by the phase.

As the amount of blast cells increases in the blood and bone marrow, there is less room for healthy blood cells. The amount of blast cells in the blood and bone marrow and the severity of symptoms (infections, anemia, easy bleeding, bone pain, and pain below the ribs on the left side) determine the phase of the disease.

• Chronic phase – in the chronic phase of CML, 5% or fewer of the cells in the blood and bone marrow are blast cells.


• Accelerated phase – in the accelerated phase of CML, 6% to 20% of the cells in the blood and bone marrow are blast cells.


• Blastic phase – in the blastic phase of CML, more than 20% of the cells in the blood and bone marrow are blast cells.

What are the treatment options?

Most patients are initially treated with Imatinib or Gleevec, a pill from a class of drugs known as tyrosine kinase inhibitors. It is a very effective treatment although we do not yet know if it can cure the disease. The only known cure is allogeneic transplant, which can cure 60-80% of patients in the chronic phase, but is quite risky as well. It is very important to discuss the possibility of stem cell transplantation for almost all patients who have CML.

Chronic Phase CML Treatments:

• Allogeneic stem cell transplantation

Accelerated Phase CML Treatments:

• Allogeneic stem cell transplantation


• Other drug therapy (Gleevec)


• Experimental therapy

Blastic Phase CML Treatments:

• Experimental therapy


• Increase Gleevec doses


• Allogeneic stem cell transplantation


• Chemotherapy or palliative therapy to relieve symptoms and improve quality of life

In 1998 a study conducted by the Fred Hutchinson Cancer Research Center showed that 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.