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Chronic myeloid leukemia

CML, Chronic myelocytic leukemia, CGL, Chronic myelogenous leukemia, Chronic granulocytic leukemia

Overview

Chronic myelogenous (myeloid)  leukemia (CML) is an uncommon type of cancer of the blood cells. The term "chronic" in chronic myelogenous leukemia indicates that this cancer tends to progress more slowly than acute forms of leukemia. The term "myelogenous" refers to the type of cells affected by this cancer. Chronic myelogenous leukemia typically affects older adults and rarely occurs in children, though it can occur at any age.

The phase of chronic myelogenous leukemia refers to the aggressiveness of the disease.  A higher proportion of diseased cells means chronic myelogenous leukemia is at a more advanced stage.

Phases of chronic myelogenous leukemia include:

  • Chronic. The chronic phase is the earliest phase and generally has the best response to treatment
  • Accelerated. The accelerated phase is a transitional phase when the disease becomes more aggressive
  • Blastic. Blastic phase is a severe, aggressive phase that becomes life-threatening

Symptoms - Chronic myeloid leukemia

Signs and symptoms of chronic myelogenous leukemia 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)

Causes - Chronic myeloid leukemia

Develpment of abnormal chromosome

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 chronic myelogenous leukemia.

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 protein called tyrosine kinase. Tyrosine kinase promotes cancer by allowing certain blood cells to grow out of control.

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 chronic myelogenous leukemia, this process doesn't work properly. The tyrosine kinase caused by the BCR-ABL gene causes too many white blood cells. Most or all of these cells contain the abnormal Philadelphia chromosome.
Factors that increase the risk of chronic myelogenous leukemia:

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

Prevention - Chronic myeloid leukemia

Not known.

Diagnosis - Chronic myeloid leukemia

Tests and procedures used to diagnose chronic myelogenous leukemia include:

  • Physical exam. Your doctor will examine you and check such vital signs as pulse and blood pressure. He or she will also feel your lymph nodes, spleen and abdomen for abnormalities.
  • Blood tests. A complete blood count 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 the polymerase chain reaction (PCR) test, analyze blood or bone marrow samples for the presence of the Philadelphia chromosome or the BCR-ABL gene.

Prognosis - Chronic myeloid leukemia

Chronic myelogenous leukemia (CML) can cause a variety of complications, including:

  • Fatigue. If diseased white blood cells crowd out healthy red blood cells, anemia may result. Anemia can make you feel tired and worn down. Treatment for CMLalso can cause a drop in red blood cells.
  • Excess bleeding. Blood cells called platelets help control bleeding by plugging small leaks in blood vessels and helping your blood to clot. A shortage of blood platelets (thrombocytopenia) can result in easy bleeding and bruising, including frequent or severe nosebleeds, bleeding from the gums, or tiny red dots caused by bleeding into the skin (petechiae).
  • Pain. CML can cause bone pain or joint pain as the bone marrow expands when excess white blood cells build up.
  • Enlarged spleen. Some of the extra blood cells produced when you have CML are stored in the spleen. This can cause the spleen to become swollen or enlarged. The swollen spleen takes up space in your abdomen and makes you feel full even after small meals or causes pain on the left side of your body below your ribs.
  • Infection. White blood cells help the body fight off infection. Although people with CML have too many white blood cells, these cells are often diseased and don't function properly. As a result, they aren't able to fight infection as well as healthy white cells can. In addition, treatment can cause your white cell count to drop too low (neutropenia), also making you vulnerable to infection.
  • Death. If CML can't be successfully treated, it ultimately is fatal.

Treatment - Chronic myeloid leukemia

The goal of chronic myelogenous leukemia 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's not possible to eliminate all diseased cells, but treatment can help achieve a long-term remission of the disease.

Targeted drugs:

Targeted drugs are designed to attack cancer by focusing on a specific aspect of cancer cells that allows them to grow and multiply. In chronic myelogenous leukemia, 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)
  • Ponatinib (Iclusig)

Targeted drugs are the initial treatment for most people diagnosed with chronic myelogenous leukemia. If the disease doesn't respond or becomes resistant to the first targeted drug, doctors may consider other targeted drugs, such as omacetaxine (Synribo), or other treatments. Side effects of these targeted drugs include swelling or puffiness of the skin, nausea, muscle cramps, rash, fatigue, diarrhea, and skin rashes.

Doctors haven't determined a safe point at which people with chronic myelogenous leukemia can stop taking targeted drugs. For this reason, most people continue to take targeted drugs even when blood tests reveal a remission of chronic myelogenous leukemia.

 Blood stem cell transplant

A blood stem cell transplant, also called a bone marrow transplant, offers the only chance for a definitive cure for chronic myelogenous leukemia. However, it's usually reserved for people who haven't 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

Chemotherapy drugs are typically combined with other treatments for chronic myelogenous leukemia. Often, chemotherapy treatment for chronic myelogenous leukemia is given as a tablet you take by mouth. Side effects of chemotherapy drugs depend on what drugs you take.

Biological therapy

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 don't work or if you can't take other drugs, such as during pregnancy. Side effects of interferon include fatigue, fever, flu-like symptoms and weight loss.

Alternative therapy

No alternative medicines have been found to treat chronic myelogenous leukemia. But alternative medicine may help you cope with the stress of a chronic condition and the side effects of cancer treatment. Talk to your doctor about your options, such as:

  • Acupuncture
  • Aromatherapy
  • Massage
  • Meditation
  • Relaxation techniques

Resources - Chronic myeloid leukemia

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