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Leukemia - Chronic Myeloid - CML - Overview

This section has been reviewed and approved by the Cancer.Net Editorial Board, 08/2014

ON THIS PAGE: You will find some basic information about this disease and the parts of the body it may affect. This is the first page of Cancer.Net’s Guide to Chronic Myeloid Leukemia. To see other pages, use the menu on the side of your screen. Think of that menu as a roadmap to this full guide.

About leukemia

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. Bone marrow is the spongy, red tissue in the inner part of large bones. CML most often causes an increase in the number of white blood cells, such as neutrophils or granulocytes, that normally fight infection. It is also sometimes called chronic granulocytic, chronic myelocytic, or chronic myelogenous leukemia. About 10% of people with leukemia have CML.

About the Philadelphia Chromosome

People with CML have a genetic mutation or change in their bone marrow cells that they develop from damage that occurs by chance after they are born, and there is no risk of passing on the gene to their children. This specific mutation is called a translocation, which means that part of a long strand of genes called a chromosome breaks off and reattaches to another chromosome. 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. This causes two genes called BCR and ABL to become one fusion gene called BCR-ABL. It is found only in the blood-forming cells, not in other organs of the body. The BCR-ABL gene causes myeloid cells to make an abnormal enzyme, called a fusion protein, 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 that help the blood to clot often increase, and the number of red blood cells, which carry oxygen, may decrease.

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If you would like additional introductory information, explore these related items. Please note that these links take you to other sections on Cancer.Net:

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Leukemia - Chronic Myeloid - CML - Statistics

This section has been reviewed and approved by the Cancer.Net Editorial Board, 08/2014

ON THIS PAGE: You will find information about how many people learn they have CML each year and some general survival information. Remember, survival rates depend on several factors. To see other pages, use the menu on the side of your screen.

This year, an estimated 5,980 people of all ages (3,130 men and boys and 2,850 women and girls) in the United States will be diagnosed with CML. Most of these will be adults; CML is rare in children. It is estimated that 810 deaths (550 men and boys and 260 women and girls) will occur this year.

The five-year survival rate is the percentage of people who survive at least five years after the cancer is detected, excluding those who die from other diseases. The five-year survival rate of people with CML depends on the phase of the disease, other biologic characteristics of the CML, and the disease’s response to treatment. The pace of CML research is rapid, with several drug approvals in the past decade. It is important to note that many of the new drugs for CML work very well, and survival rates are continually being measured based on these newer drugs.

Due in large part to recent scientific advances in the area of targeted treatments like imatinib (Gleevec), the five-year survival rate for CML has nearly doubled from 31% for people diagnosed between 1990 and 1992 to 59% for those diagnosed between 2003 and 2009, which is the most recent data available. Because survival statistics are measured in five-year intervals, they may not represent all of the recent significant advances made in the treatment and diagnosis of CML. In one study of patients with CML who were consistently taking the drug imatinib, researchers found that 90% lived at least five years.

Cancer survival statistics should be interpreted with caution. These estimates are based on data from thousands of people with this type of cancer in the United States each year, but the actual risk for a particular individual may differ. It is not possible to tell a person how long he or she will live with CML. Learn more about understanding statistics.

Statistics adapted from the American Cancer Society's publication, Cancer Facts and Figures 2014.

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Leukemia - Chronic Myeloid - CML - Risk Factors

This section has been reviewed and approved by the Cancer.Net Editorial Board, 08/2014

ON THIS PAGE: You will find out more about the factors that increase the chance of developing this type of leukemia. To see other pages, use the menu on the side of your screen.

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 years. CML is uncommon in children and teens.

Radiation exposure. More people who were long-term survivors of the 1945 atomic bombings in Japan were diagnosed with CML. However, there is no proven link between CML and radiation therapy or chemotherapy given for other types of cancer or other diseases.

Gender. Men are somewhat more likely to develop CML than women.

To continue reading this guide, use the menu on the side of your screen to select another section.

Leukemia - Chronic Myeloid - CML - Symptoms and Signs

This section has been reviewed and approved by the Cancer.Net Editorial Board, 08/2014

ON THIS PAGE: You will find out more about body changes and other things that can signal a problem that may need medical care. To see other pages, use the menu on the side of your screen.

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.

  • Fatigue or weakness, such as shortness of breath while doing everyday activities
  • Fever
  • 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.
  • Feeling full when you have not eaten much
  • Itching
  • Bone pain
  • Bleeding
  • Infections

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.

If you are concerned about one or more of the symptoms or signs on this list, please talk with your doctor. Your doctor will ask how long and how often you’ve been experiencing the symptom(s), in addition to other questions. This is to help find out the cause of the problem, called a diagnosis.

If leukemia is diagnosed, relieving symptoms 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.

The next section helps explain what tests and scans may be needed to learn more about the cause of the symptoms. Use the menu on the side of your screen to select Diagnosis, or you can select another section, to continue reading this guide.

Leukemia - Chronic Myeloid - CML - Diagnosis

This section has been reviewed and approved by the Cancer.Net Editorial Board, 08/2014

ON THIS PAGE: You will find a list of the common tests, procedures, and scans that doctors can use to find out what’s wrong and identify the cause of the problem. To see other pages, use the menu on the side of your screen.

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. This list describes options for diagnosing CML, and not all tests listed will be used for every person. Your doctor may consider these factors when choosing a diagnostic test:

  • Age and medical condition
  • Type of cancer suspected
  • Signs and symptoms
  • Previous test results

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

Blood tests. Many people are diagnosed with CML through a blood test called a complete blood count (CBC) before they have any symptoms. A CBC counts the number of different kinds of cells in the blood. A CBC is often done as part of a regular office visit. 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, a condition called anemia, and either elevated or decreased numbers of platelets.

Bone marrow aspiration and biopsy. These two procedures are similar and often done at the same time to examine the bone marrow. Bone marrow has both a solid and a liquid part. A bone marrow aspiration removes a sample of the fluid with a needle. A bone marrow biopsy is the removal of a small amount of solid tissue using a needle. The sample(s) are then analyzed by a pathologist or a hematologist. A pathologist is a doctor who specializes in interpreting laboratory tests and evaluating cells, tissues, and organs to diagnose disease. A hematologist is a doctor who specializes in treating blood disorders. A cytogenetic analysis (see below) may also be done on the marrow samples. A common site for a bone marrow aspiration and biopsy is the iliac crest of the pelvic bone (see the Medical Illustrations section), 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 testing the leukemia cells for specific genes, proteins, and other factors unique to the leukemia. Results of these tests will help determine whether your treatment options include a type of treatment called targeted therapy (see the Treatment Options section).

Cytogenetics is a type of genetic testing that is used to analyze a cell’s chromosomes, including the number, size, shape, and arrangement of the chromosomes. Occasionally, this test can be done on the peripheral or circulating blood when the CML is first diagnosed, but immature blood cells that are actively dividing need to be used. Because of this, a bone marrow sample (see above) is usually the best way to get a sample for testing.

After treatment begins, cytogenetic and/or molecular 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 (Ph+) chromosome and the BCR-ABL fusion gene (described in the Overview section), so the presence of these changes confirms 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. In this situation, 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 these diseases 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:

  • Fluorescence 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 can be 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 typically uses a blood sample rather than 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 and measure 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. A computer then combines these images into a detailed, cross-sectional view that shows any abnormalities. Sometimes, a special dye called a contrast medium is given before the scan to provide better detail on the image. This dye can be injected into a patient’s vein or given as a pill to swallow.
  • An ultrasound uses high-frequency sound waves to create a picture of the inside of the body.

After diagnostic tests are done, your doctor will review all of the results with you. If the diagnosis is CML, these results also help the doctor describe the phase of the disease.

The next section helps explain the different phases of CML. Use the menu on the side of your screen to select Stages, or you can select another section, to continue reading this guide.

Leukemia - Chronic Myeloid - CML - Phases

This section has been reviewed and approved by the Cancer.Net Editorial Board, 08/2014

ON THIS PAGE: You will learn about how doctors describe the growth or spread of CML. This is called the phase. To see other pages, use the menu on the side of your screen.

To help doctors plan treatment and predict prognosis, which is the 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, which are immature white blood cells. 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. There is no one definition of accelerated phase, although most patients with this phase of CML have 10% to 19% blasts in both the blood and bone marrow or more than 20% basophils in the peripheral blood. These cells sometimes have new cytogenetic changes in addition to the Philadelphia chromosome, because of additional DNA damage and mutations in the CML cells.
 
Blast phase, also called blast crisis. In the blast phase, there are 20% or more blasts in the blood or bone marrow or the leukemia blasts have spread outside of the bone marrow, and it is difficult to control the number of white blood cells. Additional genetic changes are also often found in the CML cells. The blast cells can look like the immature cells seen in acute lymphoblastic leukemia for about 25% of patients or acute myeloid leukemia for most patients. Patients in blast crisis often have a fever, an enlarged spleen, weight loss, and generally feel unwell.

Recurrent CML. Recurrent CML is CML that has come back after treatment.

Without effective treatment, CML in chronic phase will eventually move into accelerated phase at first and then into blast crisis in about six to eight years after diagnosis. Patients who have more blasts or an increased number of a special type of white blood cell called a basophil, chromosome changes in addition to the Philadelphia chromosome, high numbers of white blood cells, or a very enlarged spleen often experience blast crisis sooner.

Information about the phase of CML will help the doctor recommend a treatment plan. The next section helps explain the treatment options for CML. Use the menu on the side of your screen to select Treatment Options, or you can select another section, to continue reading this guide.

Leukemia - Chronic Myeloid - CML - Treatment Options

This section has been reviewed and approved by the Cancer.Net Editorial Board, 08/2014

ON THIS PAGE: You will learn about the different ways doctors use to treat people with CML. To see other pages, use the menu on the side of your screen.

This section outlines treatments that are the standard of care (the best proven treatments available) for this specific type of cancer. When making treatment plan decisions, patients are also encouraged to consider clinical trials as an option. A clinical trial is a research study to test a new approach to treatment to prove it is safe, effective, and possibly better than the standard treatment. Clinical trials may test such approaches as a new drug, a new combination of standard treatments, or new doses of current therapies. Your doctor can help you review all treatment options. For more information, see the Clinical Trials and Latest Research sections.

Treatment overview

In cancer care, different types of doctors often work together to create a patient’s overall treatment plan that combines different types of treatments. This is called a multidisciplinary team.

Descriptions of the most common treatment options for CML are listed below, followed by information on measuring treatment effectiveness and the common treatment recommendations outlined by the disease phase. Treatments for CML have improved greatly in the last 12 years, completely changing how treatment is given and helping many patients live longer.

Treatment options and recommendations depend on several factors, including the phase of the disease, possible side effects, and the patient’s preferences and overall health. Your care plan may also include treatment for symptoms and side effects, an important part of cancer care. Take time to learn about all of your treatment options and be sure to ask questions about things that are unclear. Also, talk about the goals of each treatment with your doctor and what you can expect while receiving the treatment. It is also important to talk with your health care team about the costs of treatment, as many of the drugs discussed below need to be continued throughout a person’s life. Learn more about making treatment decisions.

Targeted therapy

Targeted therapy is a treatment that attacks the cancer’s specific genes, proteins, or the tissue environment that contributes to cancer growth and survival. This type of treatment blocks the growth and spread of cancer cells while limiting damage to healthy cells. For CML, targeted therapy is given by a medical oncologist, a doctor who specializes in treating cancer with medication, or a hematologist.

Recent studies show that not all cancers have the same targets. To find the most effective treatment, your doctor may run tests to identify the genes, proteins, and other factors involved in your leukemia. As a result, doctors can better match each patient with the most effective treatment whenever possible. In addition, many research studies are taking place now to find out more about specific molecular targets and new treatments directed at them. Learn more about targeted treatments.

For CML, the target is the unique protein called the BCR-ABL tyrosine kinase enzyme. There are five drugs currently used to target tyrosine kinase enzymes for CML, called tyrosine kinase inhibitors or TKIs: imatinib (Gleevec), dasatinib (Sprycel), nilotinib (Tasigna), bosutinib (Bosulif), and ponatinib (Iclusig). All five drugs can stop the BCR-ABL enzyme from working, which causes the CML cells to die quickly. These drugs are described in more detail below.

It is important to note that men and women taking TKIs should avoid fathering a child or becoming pregnant while taking the drugs because of risk to the developing child. To find the best treatment, patients should talk with their doctors about the risks and benefits of these drugs, including the possible side effects and how they can be managed. If a patient experiences too many side effects, another TKI can be used instead.

Imatinib. Imatinib was the first targeted therapy approved by the U.S Food and Drug Administration (FDA) for CML in 2001. It is taken as a pill once or twice a day and causes fewer side effects than the chemotherapy (see below) used to treat CML in the past. Nearly all patients with chronic phase CML have their blood counts return to normal and their spleen shrink after receiving this drug. Most importantly, 80% to 90% of patients newly diagnosed with chronic phase CML who receive imatinib no longer have detectable levels of cells with the Philadelphia chromosome. Imatinib may also be used to treat some adults with other types of cancer, such as acute lymphoblastic leukemia (ALL) with the presence of the Philadelphia chromosome.

The risk of recurrence for patients whose CML completely responds to imatinib is very low, and patients with few numbers of cells with the Philadelphia chromosome remaining will stay in chronic phase longer by taking imatinib than they might have with previous treatments. Although it is too soon to know how long these responses will last or if patients will be cured with this medication alone, there are many patients who have been treated with imatinib since the first clinical trials in 1999 who still have no detectable cells with the Philadelphia chromosome.

The side effects of imatinib are mild but can include slight nausea, which is very uncommon when imatinib is taken with food, changes in blood counts, fluid retention, swelling around the eyes, fatigue, diarrhea, and muscle cramps.

Dasatinib. Dasatinib is approved by the FDA as an initial treatment for patients with newly-diagnosed chronic phase CML and when other drugs are not working. It is a pill that may be taken once or twice a day depending on the dose. The side effects include anemia, a low level of white blood cells called neutropenia, a low level of platelets called thrombocytopenia, and the build-up of fluid around the lungs or heart. The doctor will monitor a patient’s blood counts frequently after starting dasatinib and may adjust the dose or stop giving the drug temporarily if the patient’s blood counts drop too low. Dasatinib may also cause bleeding, fluid retention, diarrhea, rash, headache, fatigue, and nausea. Dasatinib requires stomach acid in order to be absorbed so patients should not take anti-acid medications.

Nilotinib. Nilotinib is also approved by the FDA as an initial treatment for patients with newly-diagnosed chronic phase CML and when other drugs are not working. It is a capsule that patients take by mouth twice a day on an empty stomach. Common side effects include low blood counts, rash, headache, nausea, diarrhea, and itching. Other possible but uncommon serious side effects include high blood sugar levels, fluid build up, and swelling of the pancreas or liver. The most serious side effect of nilotinib includes possibly life-threatening heart and blood vessel problems that can lead to an irregular heartbeat, stroke, and possible sudden death. However, this side effect is very rare. However, there can be interactions with other medications that may increase these risks, so be sure to talk with your doctor about all medications you are taking.

Bosutinib. In 2012, bosutinib was approved by the FDA to treat CML when one of the other TKIs was not effective or if a patient experienced too many side effects. The most common side effects include diarrhea, nausea and vomiting, low levels of blood cells, abdominal pain, fatigue, fever, allergic reactions, and liver problems.  

Ponatinib. Ponatinib was also approved by the FDA in 2012 for patients when one of the other TKIs was not effective or if a patient experienced too many side effects. Ponatinib also targets CML cells that have a particular mutation, known as T315I, which makes these cells resistant to other currently approved TKIs. The most common side effects include high blood pressure, rash, abdominal pain, fatigue, headache, dry skin, constipation, fever, joint pain, and nausea. The FDA also warns that this drug may cause heart problems, severe narrowing of blood vessels, blood clots, stroke, or liver problems.

Measuring treatment effectiveness. Patients receiving a TKI should receive regular check-ups with the health care team to see how well the treatment is working. The response of CML includes:

  • A complete hematologic response: the white blood cell and platelet counts have returned to normal, the spleen is of normal size and cannot be felt on physical examination, and there are no CML symptoms.
  • A partial response: the blood counts are still abnormal, there may still be some blasts in the blood, and the spleen may still be enlarged, but the symptoms and blood test results have improved since treatment began. These responses are not stable, and there is a risk that the CML will worsen without more effective treatment. Sometimes this means continuing on the current TKI to see if the treatment helps further or it may mean changing to another TKI.

Other specific tests are used to find the number of cells that have the Philadelphia chromosome or contain the BCR-ABL fusion gene. When CML is diagnosed, the Philadelphia chromosome is found in almost all of a person’s bone marrow and blood cells. Once a person’s CML shows a complete hematologic response, the doctor then looks for a cytogenetic response with tests such as FISH (see Diagnosis).

  • A complete cytogenetic response means that there are no cells with the Philadelphia chromosome found on the routine cytogenetic tests.
  • A partial cytogenetic response means that between 1% and 35% of the cells still have the Philadelphia chromosome.
  • A minor cytogenetic response means that more than 35% of the cells still have the Philadelphia chromosome.

A molecular response is when the PCR test is used to find the BCR-ABL fusion gene. A major molecular response means that a very small number of cells (more than 1,000 times fewer than when diagnosed) with the BCR-ABL fusion gene are found in the bone marrow or peripheral blood. A complete molecular response is when no cells with the BCR-ABL fusion gene are found in the bone marrow or peripheral blood.

An important goal of treatment is to achieve a complete cytogenetic response. This requires performing a bone marrow biopsy and is generally done three to six months after starting treatment when blood tests suggest that there are fewer leukemia cells. It is not clear whether any of these drugs can cure CML, and the disease may come back if treatment is stopped. If treatment with one of these drugs has worked, a patient no longer has evidence of cells with the Philadelphia chromosome and has normal levels of blood cells. This is called a complete cytogenetic remission. It is currently recommended that these drugs should be continued throughout the person’s life to prevent the CML from recurring.

Monitoring. More sensitive blood tests, such as PCR and rarely FISH (see Diagnosis), are usually done every three months on a blood sample after a person has a cytogenetic response in the bone marrow cells. Patients who have no cells with the Philadelphia chromosome on regular cytogenetic tests often need to have PCR testing to find a molecular response. Patients who have a rapid decrease in the number of cells with the Philadelphia chromosome by three months after starting treatment may have the best long-term outcomes.

The most sensitive test to look for remaining CML is called a quantitative reverse transcriptase PCR (Q-RT-PCR) test. This test is recommended every three months on a blood sample. Generally, this test can find one CML cell remaining among 1 million normal blood cells, so, when this test is negative, it is very likely that the CML is nearly gone. On the other hand, if the results of this test begin to rise, then the current treatment is no longer working, and it may be time to switch medications before the disease recurs.

Sometimes, a TKI stops working and the CML develops resistance to it. Resistance can occur if patients do not take their medication regularly, as prescribed, so it is important for patients to take their medication as prescribed. Even if patients do take the medication correctly, CML may become resistant to a TKI, which is why it is important to receive regular monitoring with cytogenetic testing, FISH, or PCR to monitor how well the drug is continuing to work.

Both dasatinib and nilotinib have been shown to bring about a complete cytogenetic response sooner and in more patients newly diagnosed with CML when compared with imatinib; however, imatinib has been used for longer. There is no difference in overall survival when using either imatinib or another one of these other drugs as initial treatment. Bosutinib and ponatinib are newer drugs but both have also produced complete cytogenetic responses in patients with CML. Because of possible severe side effects, caution and careful monitoring is needed if ponatinib is recommended after other drugs have stopped working. However, ponatinib is the only TKI that works for patients with the T315I mutation. If the medication you start with stops working, the dose may be increased or a different TKI may still be effective.

Chemotherapy

Chemotherapy is the use of drugs to destroy cancer cells, usually by stopping the cancer cells’ ability to grow and divide. Chemotherapy is given by a medical oncologist or a hematologist.

Systemic chemotherapy is delivered through the bloodstream to reach cancer cells throughout the body. Common ways to give chemotherapy include an intravenous (IV) tube placed into a vein using a needle or in a pill or capsule that is swallowed (orally). Chemotherapy can also be given by an injection under the skin called a subcutaneous injection. A chemotherapy regimen (schedule) usually consists of a specific number of cycles given over a set period of time. A patient may receive one drug at a time or combinations of different drugs at the same time.

A drug called hydroxyurea (Hydrea, Droxia) is often given to lower the number of white blood cells until CML can be diagnosed with the tests described in the Diagnosis section. Given in capsule form, this drug works well to return blood cells to normal levels within a few days or weeks and reduce the size of the spleen, but it does not reduce the percentage of cells with the Philadelphia chromosome and does not prevent blast crisis alone. Although hydroxyurea has few side effects, most patients newly diagnosed with chronic phase CML receive imatinib or another TKI (see above) as soon as possible. Side effects of chemotherapy depend on the specific drug and the dosage and usually go away when treatment is complete.

In 2012, the drug omacetaxine mepesuccinate (Synribo) was approved by the FDA for patients with chronic or accelerated phase CML that is not responding to one of the TKIs described above. Omacetaxine is given by injection under the skin daily for seven to 14 days. The most common side effects include thrombocytopenia, anemia, neutropenia, diarrhea, nausea, fatigue, weakness, skin irritation where the drug was given, fever, and infection.

Learn more about chemotherapy and preparing for treatment. The medications used to treat cancer are continually being evaluated. Talking with your doctor is often the best way to learn about the medications prescribed for you, their purpose, and their potential side effects or interactions with other medications. Learn more about your prescriptions by using searchable drug databases.

Stem cell transplantation/bone marrow transplantation

A stem cell transplant is a medical procedure in which bone marrow that contains leukemia is replaced by highly specialized cells, called hematopoietic stem cells, that develop into healthy bone marrow. Hematopoietic stem cells are blood-forming cells found both in the bloodstream and in the bone marrow. Today, this procedure is more commonly called a stem cell transplant, rather than bone marrow transplant, because it is the stem cells in the blood that are typically being transplanted, not the actual bone marrow tissue.

Before recommending transplantation, doctors will talk with the patient about the risks of this treatment and consider several other factors, such as the type of leukemia, results of any previous treatment, and patient’s age and general health.

There are two types of stem cell transplantation depending on the source of the replacement blood stem cells: allogeneic (ALLO) and autologous (AUTO). ALLO uses donated stem cells, while AUTO uses the patient’s own stem cells. In both types, the goal is to destroy all of the cancer cells in the marrow, blood, and other parts of the body using high doses of chemotherapy and/or radiation therapy and then allow replacement blood stem cells to create healthy bone marrow. Only ALLO transplants are used to treat CML.

Learn more about stem cell and bone marrow transplantation.

Immunotherapy

Immunotherapy, also called biologic therapy, is designed to boost the body's natural defenses to fight the cancer. It uses materials made either by the body or in a laboratory to improve, target, or restore immune system function. Interferon (Roferon-A, Intron A, Alferon, Infergen) is a type of immunotherapy. It can reduce the number of white blood cells and sometimes decrease the number of cells that have the Philadelphia chromosome.

Interferon is given daily or weekly by an injection under the skin and sometimes causes flu-like side effects, such as fever, chills, fatigue, and loss of appetite. When given on an ongoing basis, it can also cause loss of energy and memory changes. Interferon therapy was the primary treatment for chronic phase CML before imatinib became available. However, interferon is no longer recommended as the first treatment for CML because research has shown that imatinib works better to treat CML and causes fewer side effects. Learn more about immunotherapy.

Getting care for symptoms and side effects

Leukemia and its treatment often cause side effects. In addition to treatment to slow, stop, or eliminate the disease, an important part of care is relieving a person’s symptoms and side effects. This approach is called palliative or supportive care, and it includes supporting the patient with his or her physical, emotional, and social needs.

Palliative care can help a person at any stage of illness. People often receive treatment for the leukemia and treatment to ease side effects at the same time. In fact, patients who receive both often have less severe symptoms, better quality of life, and report they are more satisfied with treatment.

Palliative treatments vary widely and often include medication, nutritional changes, relaxation techniques, and other therapies. You may also receive palliative treatments similar to those meant to eliminate the leukemia, such as chemotherapy, surgery, and radiation therapy. Talk with your doctor about the goals of each treatment in your treatment plan.

Before treatment begins, talk with your health care team about the possible side effects of your specific treatment plan and supportive care options. And during and after treatment, be sure to tell your doctor or another health care team member if you are experiencing a problem so it is addressed as quickly as possible. Learn more about palliative care.

Treatment by phase

Chronic phase

The immediate goals of treatment are to reduce any symptoms of CML. The longer-term goals are to decrease or get rid of the cells with the Philadelphia chromosome to slow down or prevent the disease from moving to blast crisis. Treatment will often first include one of the TKIs mentioned above. An ALLO stem cell transplantation would be considered afterwards only if the TKI treatment does not work.

Accelerated phase

The same drugs used for chronic phase CML may also be used for accelerated phase CML. Although treatment with a TKI can work well for accelerated phase CML, it is less likely to work as well as it does for chronic phase CML. Dasatinib or nilotinib are more effective in providing longer remissions, but many patients have a recurrence within about two years. Therefore, an ALLO stem cell transplantation should be considered when possible. If an ALLO stem cell transplantation is not recommended or if a matched donor cannot be found, the treatment plan may include a different TKI or a clinical trial.

Blastic phase

Treatment with a TKI only works well for a few months for patients in blast crisis, but it can help to control the CML while a stem cell/bone marrow transplant is being arranged. If the transplant can be done while imatinib or dasatinib is working, then the long-term results are better. Stem cell/bone marrow transplantation in the blast phase is less successful than in chronic phase, but this approach has worked well for some patients. Many people with CML in blastic phase receive imatinib or dasatinib plus chemotherapy similar to that used for patients with acute leukemia, such as acute myeloid leukemia (AML) or acute lymphoblastic leukemia (ALL). The chance of remission from this approach is about 20% to 30%, although the leukemia recurs for most patients within weeks to a few months. Hydroxyurea (see Chemotherapy, above) is often given to patients because it can help control blood cell levels. If stem cell/bone marrow transplantation is not an option, the doctor may recommend a clinical trial.

Refractory CML

If the leukemia does not respond to treatment, it is called refractory leukemia. Patients with this diagnosis are encouraged to talk with doctors who are experienced in treating this type of leukemia, because there can be different opinions about the best treatment plan. Learn more about seeking a second opinion before starting treatment, so you are comfortable with the treatment plan chosen. This discussion may include clinical trials. Supportive care will also be important to help relieve symptoms and side effects.

For most patients, a diagnosis of refractory leukemia is very stressful and, at times, difficult to bear. Patients and their families are encouraged to talk about the way they are feeling with doctors, nurses, social workers, or other members of the health care team. It may also be helpful to talk with other patients, including through a support group.

Remission and the chance of recurrence

It is not yet proven whether imatinib, dasatinib, or nilotinib, or the newer drugs bosutinib, ponatinib, or omacetaxine can cure CML. A remission is when leukemia cannot be detected in the body by cytogenetic testing and there are no symptoms. This may also be called “no evidence of disease” or NED.

A remission can be temporary or permanent. This uncertainty leads to many survivors feeling worried or anxious that the leukemia will come back. While many remissions are permanent, it is important to talk with your doctor about the possibility of the disease returning. Understanding the risk of recurrence and the treatment options may help you feel more prepared if the leukemia does return. Learn more about coping with the fear of recurrence.

If the leukemia does return despite the original treatment, it is called recurrent leukemia. When this occurs, a cycle of testing will begin again to learn as much as possible about the recurrence, including whether the leukemia is in a different phase. After testing is finished, you and your doctor will talk about your treatment options. Often the treatment plan will include the therapies described above such as targeted therapy, chemotherapy, and immunotherapy, but they may be used in a different combination or given at a different dose. Your doctor may also suggest clinical trials that are studying new ways to treat this type of recurrent leukemia.

People with recurrent leukemia often experience emotions such as disbelief or fear. Patients are encouraged to talk with their health care team about these feelings and ask about support services to help them cope. Learn more about dealing with cancer recurrence.

If treatment fails

Recovery from leukemia is not always possible. If treatment is not successful, the disease may be called advanced or terminal leukemia.

This diagnosis is stressful, and this is difficult to discuss for many people. However, it is important to have open and honest conversations with your doctor and health care team to express your feelings, preferences, and concerns. The health care team is there to help, and many team members have special skills, experience, and knowledge to support patients and their families. Making sure a person is physically comfortable and free from pain is extremely important.

Patients who have advanced disease and who are expected to live less than six months may want to consider a type of palliative care called hospice care. Hospice care is designed to provide the best possible quality of life for people who are near the end of life. You and your family are encouraged to think about where you would be most comfortable: at home, in the hospital, or in a hospice environment. Nursing care and special equipment can make staying at home a workable alternative for many families. Learn more about advanced cancer care planning.

After the death of a loved one, many people need support to help them cope with the loss. Learn more about grief and loss.

The next section helps explain clinical trials, which are research studies. Use the menu on the side of your screen to select About Clinical Trials, or you can select another section, to continue reading this guide.

Leukemia - Chronic Myeloid - CML - About Clinical Trials

This section has been reviewed and approved by the Cancer.Net Editorial Board, 08/2014

ON THIS PAGE: You will learn more about clinical trials, which are the main way that new medical approaches are tested to see how well they work. To see other pages, use the menu on the side of your screen.

Doctors and scientists are always looking for better ways to treat patients with CML. To make scientific advances, doctors create research studies involving volunteers, called clinical trials.

Many clinical trials are focused on new treatments, evaluating whether a new treatment is safe, effective, and possibly better than the current (standard) treatment. These types of studies evaluate new drugs, different combinations of existing treatments, new approaches to radiation therapy or surgery, and new methods of treatment. Patients who participate in clinical trials are often among the first to receive new treatments, such as new chemotherapy, before they are widely available. However, there is no guarantee that the new treatment will be safe, effective, or better than a standard treatment.

There are also clinical trials that study new ways to ease symptoms and side effects during treatment and manage the late effects that may occur after treatment. Talk with your doctor about clinical trials regarding side effects. In addition, there are ongoing studies about ways to prevent the disease.

Patients decide to participate in clinical trials for many reasons. For some patients, a clinical trial is the best treatment option available. Because standard treatments are not perfect, patients are often willing to face the added uncertainty of a clinical trial in the hope of a better result. Other patients volunteer for clinical trials because they know that these studies are the only way to make progress in treating CML. Even if they do not benefit directly from the clinical trial, their participation may benefit future patients with CML.

Sometimes people have concerns that, by participating in a clinical trial, they may receive no treatment by being given a placebo or a “sugar pill.” The use of placebos in cancer clinical trials is rare. When a placebo is used in a study, it is done with the full knowledge of the participants. Find out more about placebos in cancer clinical trials.

To join a clinical trial, patients participate in a process known as informed consent. During informed consent, the doctor should list all of the patient’s options, so that the person understands how the new treatment differs from the standard treatment. The doctor must also list all of the risks of the new treatment, which may or may not be different from the risks of standard treatment. Finally, the doctor must explain what will be required of each patient in order to participate in the clinical trial, including the number of doctor visits, tests, and the schedule of treatment.

For specific topics being studied for CML, learn more in the Latest Research section.

Patients who participate in a clinical trial may stop participating at any time for any personal or medical reason. This may include that the new treatment is not working or there are serious side effects. Clinical trials are also closely monitored by experts who watch for any problems with each study. It is important that patients participating in a clinical trial talk with their doctor and researchers about who will be providing their treatment and care during the clinical trial, after the clinical trial ends, and/or if the patient chooses to leave the clinical trial before it ends.

Cancer.Net offers a lot of information about cancer clinical trials in other areas of the website, including a complete section on clinical trials and places to search for clinical trials for a specific type of leukemia.

The next section helps explain the areas of research going on today about CML. Use the menu on the side of your screen to select Latest Research, or you can select another section, to continue reading this guide.

Leukemia - Chronic Myeloid - CML - Latest Research

This section has been reviewed and approved by the Cancer.Net Editorial Board, 08/2014

ON THIS PAGE: You will read about the scientific research being done now to learn more about CML and how to treat it. To see other pages, use the menu on the side of your screen.

Doctors are working to learn more about CML, ways to prevent it, how to best treat it, and how to provide the best care to people diagnosed with this disease. The following areas of research may include new options for patients through clinical trials. Most cancer centers are actively involved in clinical trials aimed at increasing the number of people who are cured of CML. Always talk with your doctor about the diagnostic and treatment options best for you.

Improving current treatments. Research focused on increasing the effectiveness of CML treatments are listed below:

  • Combining imatinib with other drugs, including low-dose cytarabine (Cytosar-U), interferon, or other BCR-ABL inhibitors
  • Creating vaccines against BCR-ABL
  • Developing newer methods of stem cell transplantation aimed at decreasing the side effects
  • Evaluating other new TKIs for CML that does not respond to imatinib

Treatment to target remaining CML cells. Several laboratory studies are focused on possible treatments that may help destroy the few remaining CML cells in most patients who have received TKIs so they can stop medical treatment. One method uses inhibitors of a protein called “smoothened” made by the SMO gene in combination with BCR-ABL TKIs.

Stopping TKIs. Researchers are also looking into the safety and effectiveness of stopping TKIs after a period of time, without affecting the patient’s health and cytogenetic status.

Supportive care. Clinical trials are underway to find better ways of reducing symptoms and side effects of current CML treatments in order to improve patients’ comfort and quality of life.

Looking for More About the Latest Research?

If you would like additional information about the latest areas of research regarding CML, explore these related items that take you outside of this guide:

The next section addresses how to cope with the symptoms of the disease or the side effects of its treatment. Use the menu on the side of your screen to select Coping with Side Effects, or you can select another section, to continue reading this guide.

Leukemia - Chronic Myeloid - CML - Coping with Side Effects

This section has been reviewed and approved by the Cancer.Net Editorial Board, 08/2014

ON THIS PAGE: You will find out more about steps to take to help cope with physical, social, and emotional side effects. This page includes several links outside of this guide to other sections of this website. To see other pages, use the menu on the side of your screen.

Fear of treatment side effects is common after a diagnosis of leukemia, but it may help to know that preventing and controlling side effects is a major focus of your health care team. This is called palliative or supportive care, and it is an important part of the overall treatment plan, regardless of the stage of disease.

Common side effects from each treatment option for CML are described in detail within the Treatment Options section. Learn more about the most common side effects of cancer and different treatments, along with ways to prevent or control them. Side effects depend on a variety of factors, including the phase, the length and dosage of treatment(s), and your overall health.

Before treatment begins, talk with your doctor about possible side effects of each type of treatment you will be receiving. Ask which side effects are most likely to happen, when they are likely to occur, and what can be done to prevent or relieve them. And, ask about the level of caregiving you may need during treatment and recovery, as family members and friends often play an important role in the care of a person with CML. Learn more about caregiving.

In addition to physical side effects, there may be emotional and social effects as well. Patients and their families are encouraged to share their feelings with a member of their health care team who can help with coping strategies, including concerns about managing the cost of your cancer care.

During and after treatment, be sure to tell the health care team about the side effects you experience, even if you feel they are not serious. Sometimes, side effects can last beyond the treatment period, called a long-term side effect. A side effect that occurs months or years after treatment is called a late effect. Treatment of both types of effects is an important part of survivorship care. Learn more by reading the After Treatment section or talking with your doctor.

The next section helps explain medical tests and check-ups needed after finishing treatment. Use the menu on the side of your screen to select After Treatment, or you can select another section, to continue reading this guide.

Leukemia - Chronic Myeloid - CML - After Treatment

This section has been reviewed and approved by the Cancer.Net Editorial Board, 08/2014

ON THIS PAGE: You will read about your medical care after treatment is finished and why this follow-up care is important. To see other pages, use the menu on the side of your screen.

As treatment for CML is completed, such as after a successful stem cell/bone marrow transplantation, or continues long-term, such as treatment with targeted therapy, talk with your doctor about developing a follow-up care plan. This plan may include regular physical examinations and/or medical tests to monitor your recovery for the coming months and years.

ASCO offers treatment summary forms to help keep track of the cancer treatment you received and develop a survivorship care plan.

People treated for CML and in remission should receive lifelong follow-up examinations on a regular basis to watch for signs or symptoms of recurrence or late effects. People treated for CML are encouraged to follow established recommendations for good health, such as receiving regular immunizations, such as the flu vaccine, as well as not smoking, eating a balanced diet, maintaining a healthy weight, and receiving appropriate screening for other types of cancer. Learn more about the next steps to take in survivorship, including making positive lifestyle changes.

For many patients with CML, targeted therapy is an ongoing cancer treatment. Any decision to stop taking these drugs should be decided by a patient and doctor together, based on how well the drug continues to work and the side effects.

The next section offers a list of questions you may want to ask. Use the menu on the side of your screen to select Questions to Ask the Doctor, or you can select another section, to continue reading this guide.

Leukemia - Chronic Myeloid - CML - Questions to Ask the Doctor

This section has been reviewed and approved by the Cancer.Net Editorial Board, 08/2014

ON THIS PAGE: You will find some questions to ask your doctor or other members of your health care team, to help you better understand your diagnosis, treatment plan, and overall care. To see other pages, use the menu on the side of your screen.

Talking often with the doctor is important to make informed decisions about your health care. These suggested questions are a starting point to help you learn more about your care and treatment. You are also encouraged to ask additional questions that are important to you. You may want to print this list and bring it to your next appointment, or download Cancer.Net’s free mobile app for an e-list and other interactive tools to help manage your care.

  • What is my diagnosis?
  • Can you explain my pathology report (laboratory test results) to me?
  • What phase is the CML in?
  • Can you recommend a leukemia specialist?
  • Where is the best place for me to be treated?
  • What are my options for treatment?
  • What clinical trials are open to me? Where are they located, and how do I find out more about them?
  • What treatment plan do you recommend? Why?
  • What are the pros and cons of each option?
  • Am I a candidate for an ALLO stem cell transplantation, and when should it be considered?
  • What is the goal of each treatment? Is it to eliminate the leukemia, help me feel better, or both?
  • Do I need to start treatment right away?
  • Will the medicine for CML interfere with any of my other medications?
  • Who will be part of my health care team, and what does each member do?
  • Who will be coordinating my overall treatment and follow-up care?
  • What is my chance of remission and long-term benefit, including cure?
  • What are the possible side effects of this treatment, both in the short term and long term?
  • If I experience too many side effects, can I switch to a different treatment?
  • How will this treatment affect my daily life? Will I be able to work, exercise, and perform my usual activities?
  • Could this treatment affect my sex life? If so, how and for how long?
  • Can I stop TKI treatment to start a family? What if my partner and I conceive while I am taking a TKI?
  • What are the risks of trying to conceive a child while taking a TKI?
  • If I am worried about managing the costs related to my cancer care, who can help me with these concerns?
  • What support services are available to me? To my family?
  • Whom should I call for questions or problems?
  • How will the results of my treatment be monitored? What follow-up tests will I need, and how often will I need them?

The next section offers some more resources that may be helpful to you. Use the menu on the side of your screen to select Additional Resources, or you can select another section, to continue reading this guide.

Leukemia - Chronic Myeloid - CML - Additional Resources

This section has been reviewed and approved by the Cancer.Net Editorial Board, 08/2014

ON THIS PAGE: You will find some helpful links to other areas of Cancer.Net that provide information about cancer care and treatment. This is the final page of Cancer.Net’s Guide to Chronic Myeloid Leukemia. To go back and review other pages, use the menu on the side of your screen.

Cancer.Net includes many other sections about the medical and emotional aspects of cancer, both for the person diagnosed and their family members and friends. This website is meant to be a resource for you and your loved ones from the time of diagnosis, through treatment, and beyond. Here are a few sections that may get you started in exploring the rest of Cancer.Net:

- Search for a leukemia specialist in your local area using this free database of doctors from the American Society of Clinical Oncology.

- Review dictionary articles to help understand medical phrases and terms used in leukemia care and treatment.

- Read more about the first steps to take when newly diagnosed with leukemia.

- Find out more about clinical trials as a treatment option.

- Learn more about coping with the emotions that leukemia can bring, including those within a family or a relationship.

- Find a national, not-for-profit advocacy organization that may offer additional information, services, and support for people with this type of leukemia.

- Explore next steps a person can take after active treatment is complete.

This is the end of the Cancer.Net’s Guide to Chronic Myeloid Leukemia. Use the menu on the side of your screen to select another section to continue reading this guide.