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chronic-myeloid-leukaemia

Leukemia - Chronic Myeloid (CML)

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What is Leukemia - Chronic Myeloid (CML)?

Leukemia is a cancer of the blood. Leukemia begins when normal blood cells change and grow uncontrollably. Chronic myeloid leukemia (CML) is a cancer of the blood-forming cells, called myeloid cells, found in the bone marrow (the spongy, red tissue in the inner part of large bones). CML most often causes an increase in the number of white blood cells (neutrophils or granulocytes that normally fight infection). It is also sometimes called chronic granulocytic, chronic myelocytic, or chronic myelogenous leukemia. CML makes up about 9% of leukemias.

About the Philadelphia Chromosome

People with CML have an acquired genetic abnormality or mutation in their bone marrow cells, in which part of one chromosome (a long strand of genes) breaks off and reattaches to another chromosome. This is called a translocation. In CML, part of chromosome 9 breaks off and bonds to a section of chromosome 22, resulting in what is called the Philadelphia chromosome or Ph chromosome. The translocation t(9;22) causes two genes calledBCR and ABL to become one fusion gene called BCR-ABL. This mutation is found only in the blood-forming cells, not in other organs of the body, and it is not inherited. Therefore, there is no concern about an increased risk to other family members. The BCR-ABL gene causes myeloid cells to make an abnormal enzyme that allows white blood cells to grow out of control.

About CML

Ordinarily, the number of white blood cells is tightly controlled by the body—more white blood cells are produced during infections or times of stress, but then the numbers return to normal when the infection is cured. In CML, the abnormal BCR-ABL enzyme is like a switch that is stuck in the “on” position—it keeps stimulating the white blood cells to grow and multiply. In addition to increased white blood cells, the number of blood platelets (cells that help the blood to clot) often increase, and the number of red blood cells, which carry oxygen, may decrease.

Symptoms

People with CML may experience the following symptoms or signs. Sometimes, people with CML do not show any of these symptoms. Or, these symptoms may be caused by a medical condition that is not cancer. If you are concerned about a symptom or sign on this list, please talk with your doctor.

Fatigue or weakness, such as shortness of breath while doing everyday activities

Excessive sweating, especially at night

Weight loss

Abdominal swelling or discomfort due to an enlarged spleen. This may be particularly noticeable in the upper left part of the abdomen.

CML progresses slowly, and symptoms may not appear for a long time. The symptoms are usually mild at first and get worse slowly. Some people do not have any symptoms when they are diagnosed with CML.

Your doctor will ask you questions about the symptoms you are experiencing to help find out the cause of the problem, called a diagnosis. This may include how long you've been experiencing the symptom(s) and how often.

If leukemia is diagnosed, relieving symptoms and side effects remains an important part of care and treatment. This may also be called symptom management, palliative care, or supportive care. Be sure to talk with your health care team about symptoms you experience, including any new symptoms or a change in symptoms.

Risk Factors

A risk factor is anything that increases a person's chance of developing cancer. Although risk factors often influence the development of cancer, most do not directly cause cancer. Some people with several risk factors never develop cancer, while others with no known risk factors do. However, knowing your risk factors and talking about them with your doctor may help you make more informed lifestyle and health care choices.

The cause of CML is not known, though researchers now understand how the disease develops from genetic changes in the myeloid cells. Environmental factors account for only a small number of CML diagnoses, and family history does not appear to play a role in the development of CML.

The following factors may raise a person's risk of developing CML:

Age. The average age of a person with CML is around 60. CML is uncommon in children and adolescents.

Radiation exposure. There was an increase in the rate of CML in Japan in long-term survivors of the 1945 atomic bombings. However, there is no proven link between CML and radiation therapy or chemotherapy given for other types of cancer or other diseases.

Gender. Men have a somewhat higher risk of CML than women.

Diagnosis

Doctors use many tests to diagnose cancer and find out more about the disease. Some tests may also determine which treatments may be the most effective. For most types of cancer, a biopsy is the only way to make a definitive diagnosis of cancer. If a biopsy is not possible, the doctor may suggest other tests that will help make a diagnosis. Imaging tests may also be used. Your doctor may consider these factors when choosing a diagnostic test:

Age and medical condition

Type of cancer suspected

Severity of symptoms

Previous test results

The following tests may be used to diagnose or monitor CML:

Blood tests. Many people are diagnosed with CML before they have any symptoms through a blood test, called a complete blood count (CBC). A CBC counts the number of different kinds of cells in the blood. A CBC is often done as part of a regular physical examination. People with CML have high levels of white blood cells. When the CML is more advanced, there may also be low levels of red blood cells (called anemia) and either elevated or decreased numbers of platelets.

Bone marrow biopsy and aspiration. These two procedures are similar and often done at the same time. Bone marrow has both a solid and a liquid part. A bone marrow biopsy is the removal of a small amount of solid tissue using a needle. An aspiration removes a sample of fluid with a needle. The sample(s) are then analyzed by a pathologist (a doctor who specializes in interpreting laboratory tests and evaluating cells, tissues, and organs to diagnose disease). A cytogenetic analysis (see below) may also be done on the marrow samples. A common site for a bone marrow biopsy and aspiration is the pelvic bone, which is located in the lower back by the hip. The skin in that area is usually numbed with medication beforehand, and other types of anesthesia (medication to block awareness of pain) may be used.

Molecular testing. Your doctor may recommend running laboratory tests on the leukemia cells to identify specific genes, proteins, and other factors unique to the leukemia. Results of these tests will help decide whether your treatment options include a type of treatment called targeted therapy.

Cytogenetics is the analysis of a cell's chromosomes, including the number, size, shape, and arrangement of the chromosomes. This test can sometimes be done on the peripheral (circulating) blood when the CML is first diagnosed, but it requires immature blood cells that are actively dividing. Because of this, a bone marrow sample (see above) is usually best. After treatment begins, cytogenetic testing is repeated on another bone marrow sample to find out if there are fewer cells with the Philadelphia chromosome. All people with CML have the Philadelphia chromosome or the BCR-ABL fusion gene , so they are used to confirm the diagnosis. For a small number of patients, increased blood cell counts may suggest CML, but the patients do not have the Philadelphia chromosome or the BCR-ABL fusion gene; therefore, they do not have CML but instead have a different type of chronic myeloproliferative disease (a disease in which there are too many red blood cells, white blood cells, or platelets). Treatment of this disease is different from that of CML.

Cytogenetic testing for CML is used to monitor how well treatment is working and if it is reducing the number of cells with the Philadelphia chromosome. The following tests are sometimes used with cytogenetic testing:

Fluorescent in situ hybridization (FISH) is a test used to detect the BCR-ABL gene and to monitor the disease during treatment. This test does not require dividing cells and is done using a blood sample or bone marrow cells. This test is a more sensitive way to find CML than the standard cytogenetic tests that identify the Philadelphia chromosome.

Polymerase chain reaction (PCR) is a DNA test that can find the BCR-ABL fusion gene and other molecular abnormalities. PCR tests may also be used to monitor how well treatment is working. This test is quite sensitive and, depending on the technique used, can find one abnormal cell mixed in with approximately 1 million normal cells. This test also uses a blood sample or bone marrow cells.

Imaging tests. Doctors may use imaging tests to determine if the cancer is affecting other parts of the body. For example, a computed tomography (CT or CAT) scan or ultrasound examination is sometimes used to look at the size of the spleen in patients with CML. A CT scan creates a three-dimensional picture of the inside of the body with an x-ray machine. Sometimes, a contrast medium (a special dye) is injected into a patient's vein to provide better detail. An ultrasound is a test that uses high-frequency sound waves to produce images of the inside of the body.

Phases

To help doctors plan treatment and predict prognosis (chance of recovery), CML is divided into three different phases: chronic, accelerated, or blastic.

Chronic phase. The blood and bone marrow contain less than 5% blasts. Blasts are the most immature blood cells, and in CML, these cancerous blast cells cannot mature. This phase can last for several years, although without effective treatment the disease can progress to the accelerated or blast phases (see below). About 90% of people have chronic phase CML when they are diagnosed. Some people with chronic phase leukemia have symptoms when they are diagnosed and some do not; most symptoms go away once treatment begins.

Accelerated phase. In the accelerated phase, there are more than 5%, but less than 30% blasts in both the blood and bone marrow. These cells often have new cytogenetic changes in addition to the Philadelphia chromosome, because of additional DNA damage and mutations (changes) in the CML cells.

Blast phase (also called blast crisis). In the blast phase, there are more than 30% blasts in the blood or bone marrow. It develops when the CML cells begin behaving like acute leukemia. Patients in blast crisis often have a fever, an enlarged spleen, weight loss, and generally feel unwell.

Recurrent CML. Recurrent CML is SML that comes back after treatment.

Without effective treatment, patients with CML in chronic phase will move into blast crisis in an average of approximately five years after diagnosis. Patients who have more blasts or an increased number of cells called basophils (a special type of white blood cell), chromosome changes in addition to the Philadelphia chromosome, high numbers of white blood cells, or a very enlarged spleen often experience blast crisis sooner.

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