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Leukemia, Chronic Myeloid (CML)

Leukemia, Chronic Myeloid (CML)

Chronic myeloid leukemia is a slow-growing cancer in which the bone marrow the soft, spongy tissue in the center of bones makes too many abnormal white blood cells known as leukemic cells. This type of leukemia is also called chronic myelogenous leukemia, chronic myelocytic leukemia, or chronic granulocytic leukemia.

Risk factors

There are very few known risk factors for CML. Children of parents with CML do not have a greater risk of developing the disease. Exposure to very high doses of  ionizing radiation has been linked to CML (such as exposure during a nuclear reactor accident), but it's not clear whether radiation used for treatment raises the risk of CML. No infectious agents or chemicals are linked to the development of this leukemia. The older you are, the higher your risk.


No standard screening process exists for detecting early-stage leukemia. Doctors often find CML during routine blood tests.


During the early stages of CML, most people do not have any symptoms of the disease. When symptoms do develop, they may include:

  • Tiredness that will not go away

  • Unexplained weight loss

  • Fever

  • Shortness of breath

  • Night sweats

  • Abdominal pain from a swollen spleen

  • Poor appetite

  • Bone pain

People who have any of these symptoms should consult with their doctor. None of these symptoms proves that a person has cancer or leukemia, and a true diagnosis can be made only by a trained oncologist or hematologist.

Why CML develops

The bone marrow is where blood cells are made. There are 3 different types of blood cells that carry out different functions in the body:

  • White blood cells, which help the body fight infection and disease

  • Red blood cells, which move oxygen from the lungs throughout the body

  • Platelets, which help control bleeding by forming clots

Blood forming cells in the bone marrow are called stem cells, and they mature into various types of blood cells called blast cells (or just blasts). Lymphoblasts develop into lymphocytes, a type of white blood cell. Myeloblasts are the type of blasts that eventually mature into white blood cells, red blood cells, and platelets. In CML, myeloblasts do not mature normally. Too many of these cells develop and become a type of white blood cell called a myelocyte, and they do not function correctly. 

In nearly all patients with CML, a defect in a chromosome (the genetic material) in the leukemic cells occurs. This defect is called the Philadelphia chromosome, named for the city where it was discovered. This abnormal chromosome forms when two chromosomes in the cell swap their genetic material. It is not clear what causes this to happen. Because of this event, a protein that normally helps to regulate the production of new white blood cells in the bone marrow the Abl protein becomes stuck in the "on" position, telling the body to keep making more abnormal blood cells.

How CML is diagnosed

Some people go to their doctor because they are having some of the symptoms described above. Many people with CML do not have symptoms at the time the disease is diagnosed. In these people, the disease is found during routine blood tests.

Blood tests are done to count the different types of blood cells. A blood sample is looked at under the microscope, and if an abnormally high number of mature and maturing white blood cells are noted, a bone marrow biopsy may be done.

The bone marrow sample is taken by a needle inserted into the bone (usually at the back of the hip). A small amount of bone marrow is taken and looked at under the microscope. A diagnosis of CML is based on the finding of the Philadelphia chromosome or the BCR-ABL gene in cells of the blood or bone marrow.

The phases of CML

CML progresses through 3 phases. The number of blasts in the blood and bone marrow and the severity of symptoms help doctors determine which phase of CML a patient is in:

  • Chronic phase. In this phase there are few blasts (usually considered to be fewer than 10%) in the blood and bone marrow. There may be no symptoms of CML, or the symptoms may be mild. Most cases of CML are diagnosed at this phase.

  • Accelerated phase. The number of blast cells increases to about 10% to 19% in either peripheral blood or bone marrow.

  • Blastic phase, or blast crisis. Twenty percent or more of cells in the blood or bone marrow are blasts. Sometimes blast cells will form tumors outside of the bone marrow in the bone or lymph nodes. At this point, chronic leukemia has become an aggressive acute leukemia.

How CML is treated

Different treatment options are available for patients with CML. Targeted therapy, stem cell transplantation, chemotherapy, radiation therapy, biologic therapy, or a combination of these approaches are used.  Additionally, if the spleen is swollen, it may be removed.

The age of the patient, the phase of CML the patient is in, and other factors are considered in coming up with the best treatment plan for a patient.

Targeted therapy

Newer drugs such as imatinib, dasatinib, and nilotinib specifically target the abnormal Abl protein in CML cells. These drugs have been found to be very effective in treating CML. They are usually the first treatment tried, especially for chronic phase CML, although they are not thought to be able to bring about a cure on their own. Other targeted drugs may be tried if these drugs do not work. 

These drugs are taken daily as pills. Side effects are usually mild, but can include diarrhea, nausea, muscle pain, skin rashes, and fatigue. Another common side effect is fluid buildup around the eyes, feet, lungs, or abdomen. 

Stem cell transplantation (SCT)

SCT is the only treatment for CML known to bring about a cure in some patients. But because targeted therapies are usually so effective, doctors typically try them first before recommending SCT. Because SCT is a risky procedure that puts a great deal of strain on the body, not all patients can tolerate this treatment. This method is most successful when used in patients in the chronic phase of CML and in younger patients.

The goal of SCT is to kill the patient's damaged bone marrow (both the leukemia cells and the stem cells are in the bone marrow) and replace it with healthy bone marrow. If the transplanted stem cells take hold, they grow and produce healthy blood cells.

The first step in stem cell transplantation involves destroying the patient's existing bone marrow with high doses of 1 or more types of anticancer drugs. Sometimes radiation therapy is also used. Both healthy and unhealthy bone marrow cells are killed in this step.

Most often, the patient's bone marrow is replaced with healthy tissue from another person (the donor). This is called an allogeneic transplant. The patient receives the donor marrow through a needle into a vein, much like a blood transfusion. The donor marrow must closely match the tissue of the patient to allow the patient's body to accept the transplant. The most suitable donor is often a brother, sister, or another family member of the patient who has the same tissue type known as HLA type as the patient. If there is not a family member with the same tissue type, the doctor may search for a donor whose tissue type matches the patient. There are computerized lists of volunteer donors set up for this purpose. However, it can be difficult to find a donor whose tissue is a close enough match to use successfully.

Another approach is to use bone marrow taken from the patient. This is called an autologous transplant. This approach involves taking bone marrow from the patient and treating it with anticancer drugs with or without radiation to destroy the cancer cells. The patient then receives high-dose chemotherapy to kill the cells in the remaining bone marrow. After this step, the saved and treated bone marrow is injected through a vein back into the patient. Autologous transplants are not often used for CML. 


Called a biological therapy because it is a substance that the body makes to fight disease, interferon-alpha is given by injection. It can help slow the growth of the leukemia cells and prolong life in some patients. Other patients either do not respond or cannot tolerate the drug's side effects, which include flu-like symptoms such as fever, chills, and fatigue. Interferon-alpha may be given alone or in combination with the chemotherapy drug cytarabine (ara-C). Interferon-alpha can produce long periods where the patient is free of the signs and symptoms of CML, but it does not bring about a lasting cure as SCT can.


Hydroxyurea and busulfan are 2 oral chemotherapy drugs that are used when patients cannot receive other treatments. These drugs are usually better tolerated than interferon-alpha and can lessen the symptoms of CML. As with interferon-alpha, they do not provide a lasting cure. Other chemotherapy drugs may be tried as well. If the CML progresses to the blast phase, chemotherapy may be used to try to get the CML under control before trying a SCT. 


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