Chronic Myelogenous Leukemia

Leukemia is cancer of the white blood cells. White blood cells form in the bone marrow and help your body fight infection. In leukemia, the bone marrow produces abnormal white blood cells. These cells crowd out the healthy blood cells, making it hard for blood to do its work. In chronic myeloid leukemia (CML), there are too many granulocytes, a type of white blood cell.

CML can also be called chronic myeloid leukemia and chronic granulocytic leukemia. CML typically affects older adults and rarely occurs in children, though it can occur at any age.

Sometimes CML does not cause any symptoms. If you have symptoms, they may include:

• Fatigue
• Weight loss
• Night sweats
• Fever
• Pain or a feeling of fullness below the ribs on the left side

Treatments for CML include chemotherapy, stem cell transplants, infusion of donated white blood cells following stem cell transplants, surgery to remove the spleen, and biologic and targeted therapies. Biologic therapy boosts the body's own ability to fight cancer. Targeted therapy uses substances that attack cancer cells without harming normal cells.

Signs and symptoms of CML may include:

• Easy bleeding
• Feeling run-down or tired
• Fever
• Losing weight without trying
• Loss of appetite
• Pain or fullness below the ribs on the left side
• Pale skin
• Sweating excessively during sleep (night sweats)

CML occurs when something goes wrong in the genes of your blood cells. It is not clear what initially starts this process, but doctors have discovered how it progresses into CML.

First, an abnormal chromosome develops. Human cells normally contain 23 pairs of chromosomes. These chromosomes hold the DNA that contains the instructions (genes) that control the cells in your body. In people with chronic myelogenous leukemia, the chromosomes in the blood cells swap sections with each other. A section of chromosome 9 switches places with a section of chromosome 22, creating an extra-short chromosome 22 and an extra-long chromosome 9. The extra-short chromosome 22 is called the Philadelphia chromosome, named for the city where it was discovered. The Philadelphia chromosome is present in the blood cells of 90 percent of people with CML.

Second, the abnormal chromosome creates a new gene. The Philadelphia chromosome creates a new gene. Genes from chromosome 9 combine with genes from chromosome 22 to create a new gene called BCR-ABL. The BCR-ABL gene contains instructions that tell the abnormal blood cell to produce too much of a certain protein that promotes cancer by allowing certain blood cells to grow out of control.

Third, the new gene allows too many diseased blood cells. Your blood cells originate in the bone marrow, a spongy material inside your bones. When your bone marrow functions normally, it produces immature cells (blood stem cells) in a controlled way. These cells then mature and specialize into the various types of blood cells that circulate in your body — red cells, white cells and platelets. In CML, this process does not work properly. The protein caused by the BCR-ABL gene causes too many white blood cells and most or all of these contain the abnormal Philadelphia chromosome. The diseased white blood cells do not grow and die like normal cells. The diseased white blood cells build up in huge numbers, crowding out healthy blood cells and damaging the bone marrow.

Factors that increase the risk of CML include:

• Older age
• Being male
• Radiation exposure, such as radiation therapy for certain types of cancer

Family history is not a risk factor for CML.

Tests and procedures used to diagnose CML include:

• Physical exam. Your doctor will examine you and check vital signs such as pulse and blood pressure and feel your lymph nodes, spleen, and abdomen for abnormalities.
• Blood tests. A complete blood count (CBC) may reveal abnormalities in your blood cells. Blood chemistry tests to measure organ function may also reveal abnormalities that can help your doctor make a diagnosis.
• Bone marrow tests. Bone marrow biopsy and bone marrow aspiration are used to collect bone marrow samples for laboratory testing. These tests involve collecting bone marrow from your hipbone.
• Tests to look for the Philadelphia chromosome. Specialized tests, such as fluorescence in situ hybridization (FISH) analysis and polymerase chain reaction (PCR) test, analyze blood or bone marrow samples for the presence of the Philadelphia chromosome or the BCR-ABL gene.

Many people will live with CML for years and many will continue treatment. Self-care measures to help you adjust and cope with a chronic illness include:

• Talk to your doctor about your side effects. Powerful cancer medications can cause many side effects, but those side effects often can be managed with other medications or treatments.
• Don't stop treatment on your own. If you develop unpleasant side effects, such as skin rashes or fatigue, do not quit taking your medication without consulting your health care professionals. Likewise, do not stop taking your medications if you feel better and think your disease may be gone. If you stop taking medication, your disease can quickly and unexpectedly return, even if you have been in remission.
• Ask for help if you are having trouble coping. Having a chronic condition can be emotionally overwhelming. Tell your doctor about your feelings. Ask for a referral to a counselor or other specialist with whom you can talk or a support group that you can join.

The goal of CML treatment is to eliminate the blood cells that contain the abnormal BCR-ABL gene that causes the overabundance of diseased blood cells. For most people, it is not possible to eliminate all diseased cells, but treatment can help achieve a long-term remission of the disease.

Targeted drugs are designed to attack cancer by focusing on a specific aspect of cancer cells that allows them to grow and multiply. In CML, the target of these drugs is the protein produced by the BCR-ABL gene — tyrosine kinase. Targeted drugs that block the action of tyrosine kinase include:

• Imatinib (Gleevec)
• Dasatinib (Sprycel)
• Nilotinib (Tasigna)
• Bosutinib (Bosulif)
• Omacetaxine (Synribo)

Targeted drugs are the initial treatment for most people diagnosed with CML. If the disease does not respond or becomes resistant to the first targeted drug, doctors may consider other targeted drugs or other treatments.

A blood stem cell transplant, also called a bone marrow transplant, offers the only chance for a definitive cure for CML. However, it is usually reserved for people who have not been helped by other treatments because blood stem cell transplants have risks and carry a high rate of serious complications.

During a blood stem cell transplant, high doses of chemotherapy drugs are used to kill the blood-forming cells in your bone marrow. Then blood stem cells from a donor or your own cells that were previously collected and stored are infused into your bloodstream. The new cells form new, healthy blood cells to replace the diseased cells.

Chemotherapy drugs are typically combined with other treatments for CML. Often, chemotherapy treatment for CML is given as a tablet you take by mouth.

Biological therapies harness your body's immune system to help fight cancer. The biological drug interferon is a synthetic version of an immune system cell. Interferon may help reduce the growth of leukemia cells. Interferon may be an option if other treatments do not work or if you cannot take other drugs, such as during pregnancy.