Chronic myelogenous leukemia : A chronic malignant disease in which too many white blood cells belonging to the myeloid line of cells are made in the bone marrow . Early symptoms include fatigue and night sweats . The disease is due to the growth and evolution of an abnormal clone of cells containing a chromosome rearrangement known as the Philadelphia (or Ph) chromosome. This chromosome usually doesn't go away, even after treatment.

Chronic myelogenous leukemia is also called CML, chronic myelocytic leukemia, and chronic granulocytic leukemia)

Background: Normally, bone marrow cells called blasts develop (mature) into several different types of blood cells that have specific jobs to do in the body. CML affects the blasts that are developing into white blood cells called granulocytes. The blasts do not mature and become too numerous. These immature blast cells are then found in the blood and the bone marrow.

Leukemia can be acute (progressing quickly with many immature blasts) or chronic (progressing slowly with more mature-looking cancer cells). Chronic myelogenous leukemia progresses slowly and usually occurs in people who are middle-aged or older, although it also can occur in children. In the first stages of CML, most people don't have any symptoms of cancer. A doctor should be seen if any of the following symptoms appear: tiredness that won't go away, a feeling of no energy, fever, not feeling hungry, or having night sweats. Also, the spleen (the organ in the right upper part of the abdomen that makes other types of white blood cells and filters old blood cells from the blood) may be swollen and markedly enlarged.

If there are symptoms, a doctor may order blood tests to count the number of each of the different kinds of blood cells. If the results of the blood test are not normal, the doctor may order more blood tests. A bone marrow biopsy also may be done. During this test, a needle is inserted into a bone and a small amount of bone marrow is taken out and looked at under the microscope. The doctor can then tell what kind of leukemia the patient has and plan the best treatment.

Staging of CML: Once chronic myelogenous leukemia (CML) has been found (diagnosed), more tests may be done to find out if leukemia cells have spread into other parts of the body such as the brain. This is called staging. CML progresses through different phases and these phases are the stages used to plan treatment. The following stages are used for chronic myelogenous leukemia:

Chronic phase : There are few blast cells in the blood and bone marrow and there may be no symptoms of leukemia. This phase may last from several months to several years.

Accelerated phase: There are more blast cells in the blood and bone marrow, and fewer normal cells.

Blastic phase: More than 30% of the cells in the blood or bone marrow are blast cells. The blast phase of CML is sometimes called "blast crisis." Sometimes blast cells will form tumors outside of the bone marrow in places such as the bone or lymph nodes . Lymph nodes are small bean-shaped structures that are found throughout the body. They produce and store infection-fighting cells.

Refractory CML: Leukemia cells do not decrease even though treatment is given.

Treatment: There are treatments for all patients with CML. Three kinds of treatment are currently (as of November, 2000) in standard usage:

• Chemotherapy (using drugs to kill cancer cells);
• Radiation therapy (using high-dose x-rays or other high-energy rays to kill the leukemic cells); and
• Bone marrow transplantation (killing the bone marrow and replacing it with healthy marrow).

Chemotherapy uses drugs to kill cancer cells. Chemotherapy may be taken by pill, or it may be put into the body by a needle in the vein or muscle . Chemotherapy is called a systemic treatment because the drug enters the bloodstream, travels through the body, and can kill cancer cells throughout the body. Chemotherapy also can be put directly into the fluid around the brain and spinal cord through a tube inserted into the brain or back. This is called intrathecal chemotherapy .

Radiation therapy uses x-rays or other high-energy rays to kill cancer cells and shrink tumors. Radiation for CML usually comes from a machine outside the body ( external radiation therapy ) and is sometimes used to relieve symptoms or as part of therapy given before a bone marrow transplant .

Bone marrow transplantation is used to replace the patient's bone marrow with healthy bone marrow. First, all of the bone marrow in the body is destroyed with high doses of chemotherapy with or without radiation therapy. Healthy marrow is then taken from another person (a donor ) whose tissue is the same as or almost the same as the patient's. The donor may be an identical twin (the best match), a brother or sister, or another person not related. The healthy marrow from the donor is given to the patient through a needle in the vein, and the marrow replaces the marrow that was destroyed. A bone marrow transplant using marrow from a relative or person not related to the patient is called an allogeneic bone marrow transplant.

Another type of bone marrow transplant, called autologous bone marrow transplant, is being tested in clinical trials . To do this type of transplant, bone marrow is taken from the patient and treated with drugs to kill any cancer cells. The marrow is then frozen to save it. The patient is given high-dose chemotherapy with or without radiation therapy to destroy all of the remaining marrow. The frozen marrow that was saved is then thawed and given back to the patient through a needle in a vein to replace the marrow that was destroyed.

A greater chance for recovery occurs if a doctor chooses a hospital which does more than 5 bone marrow transplantations per year.

Biological therapy tries to get the body to fight cancer. It uses materials made by the body or made in a laboratory to boost, direct, or restore the body's natural defenses against disease. Biological therapy is sometimes called biological response modifier (BRM) therapy or immunotherapy .

If the spleen is swollen, a doctor may take out the spleen in an operation called a splenectomy .

Treatment by stage : Standard treatment may be considered because of its effectiveness in patients in past studies, or participation in a clinical trial may be considered. Most patients are not cured with standard therapy and some standard treatments may have more side effects than are desired.

Chronic Phase CML: Treatment may be one of the following:

1. High-dose chemotherapy with radiation therapy followed by bone marrow transplantation.
2. Biological therapy.
3. Chemotherapy to lower the number of white blood cells.
4. Surgery to remove the spleen (splenectomy).
5. Chemotherapy and/or radiation therapy followed by bone marrow transplantation.
6. A clinical trial evaluating new drugs.

Accelerated Phase CML: Treatment may be one of the following:

1. Bone marrow transplantation.
2. Biologic therapy.
3. High-dose chemotherapy.
4. Chemotherapy to lower the number of white blood cells.
5. Other chemotherapy drugs.
6. Transfusions of blood or blood products to relieve symptoms.
7. A clinical trial evaluating new drugs.

Blastic Phase CML: Treatment may be one of the following:

1. A clinical trial evaluating new chemotherapy drugs and/or new combinations of drugs.
2. Chemotherapy.
3. Bone marrow transplantation.
4. Chemotherapy to relieve symptoms associated with the cancer.
5. Radiation therapy to relieve symptoms caused by tumors formed in the bone.
6. High-dose chemotherapy.
7. A clinical trial evaluating new drugs.

Meningeal CML: Treatment may be one of the following:

1. Chemotherapy injected into the spinal canal.
2. Other chemotherapy drugs injected into the spinal canal.
3. Radiation therapy to the brain.

Refractory CML: The treatment depends on many factors. A patient may wish to consider entering a clinical trial. If the patient has had a bone marrow transplant, the treatment may be biological therapy or white blood cells from the bone marrow donor may be given to the patient through a vein.

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