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Understanding CML
Causes and Risk Factors
Signs and Symptoms
Diagnosis
Goals of CML Therapy
Oral CML Therapy
Side Effects of Oral CML Therapy
Stem Cell Transplantation
Clinical Trials
Tracking Treatment Response
CML-Related Disorders
Questions for the CML Specialist
Get More Information
Contact Us

Understanding CML

Leukemia is a type of cancer. CML is one of four main types of leukemia. CML starts with a change to a single stem cell. Both children and adults can get CML, but most CML patients are adults. 

About 5,050 people in the United States are expected to be diagnosed with chronic myelogenous leukemia (CML) in 2009. It is estimated that approximately 22,475 people in the United States are living with CML (SEER, National Cancer Institute, 2009). Three new CML drugs (Gleevec®, Sprycel® and Tasinga®) have been approved since 2001. Other new treatments are being studied in clinical trials. Progress toward a cure is under way and the number of people with CML who are living well today is growing. 

CML patients have what is called the "Philadelphia Chromosome" (Ph chromosome). Chromosomes are structures in the cells that contain genes. Every cell with a nucleus has chromosomes. Genes give instructions to the cells. The Ph chromosome is made when a piece of chromosome 22 breaks off and attaches to the end of chromosome 9. A piece of chromosome 9 also breaks off and attaches to the end of chromosome 22. The break on chromosome 9 involves a gene called Abl. The break on chromosome 22 involves a gene called Bcr. The Bcr and Abl genes combine to make the CML-causing gene called the Bcr-Abl cancer gene.

 
Click here for a larger image of this chart.

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Phases of CML

There are three phases of CML:

• The chronic phase
• The accelerated phase
• The blast crisis phase

Chronic Phase CML

Most patients are in the chronic phase of the disease when their CML is diagnosed. In this phase, CML symptoms are milder. White cells can still fight infection. Once patients in the chronic phase are treated, they can go back to their usual activities.

Accelerated Phase CML

In the accelerated phase, the patient may develop anemia, the number of white cells may go up or down, or the number of platelets may drop. The number of blast cells may increase and the spleen may swell. People with accelerated-phase CML may feel ill.

Blast Crisis Phase CML

Patients with blast crisis phase CML have an increased number of blast cells in the marrow and blood. The number of red cells and platelets drops. Patients may have infections or bleeding. They may also feel tired and have shortness of breath, stomach pain, or bone pain.

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Causes and Risk Factors

Doctors do not know why the Bcr-Abl gene that leads to CML forms in some people but not in others.  Some risk factors that may increase the risk of developing CML are:

However, most people treated for cancer with radiation do not develop CML. And most people with CML were not exposed to high-dose radiation. There is no link between dental or medical x-rays and increased risk of CML.

You cannot catch CML from someone else.

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Signs and Symptoms

People with CML may not have any symptoms at the time of diagnosis. They may be diagnosed following a medical examination for another condition or as part of a periodic checkup. CML signs and symptoms tend to develop gradually. Some signs and symptoms of CML are:

Many of the signs and symptoms for CML are common to other illnesses. Most people with these signs and symptoms do not have CML.

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Diagnosis

The diagnosis of CML is usually made with information from blood and bone marrow tests.

Blood Tests

The testing for CML includes blood cell counts and a blood cell examination.

• Blood cell counts. The doctor orders a test called a complete blood count to check the numbers of blood cells. With CML, the red cell count is lower than normal. The number of white cells is higher than normal and may be very high. The number of platelets may be higher or lower than normal.
  
• Blood cell examination. The cells are stained (dyed) and looked at (dyed) and looked at with an instrument called a light microscope. A person with CML has a small number of developing cells called "blast cells" in his or her blood. Blast cells are not found in the blood of healthy individuals.

Bone Marrow Tests and Cytogenetic Tests

Some signs of CML do not show in blood tests. The doctor has to look at a small number of cells (a sample) from the marrow. The samples of cells are obtained with tests known as a bone marrow aspiration and a bone marrow biopsy. 

Samples of marrow cells are examined under a microscope. This is called a cytogenetic analysis. The examiner looks at a map of the chromosomes in the cell. The map is called a "karyotype." The Ph chromosome in a CML cell can be detected on the karyotype.

FISH or fluorescence in situ hybridization is a special test used to detect CML cells that may not show up on a standard cytogenetic test for the Ph chromosome.

PCR also known as Polymerase Chain Reaction is a very sensitive test that can detect CML cells that are not found by the FISH test. This test can detect a very small number of CML cells. A PCR test can be done on cells from blood or marrow.

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Goals of CML Therapy

In the chronic phase of CML the goals of treatment are to

• Return the levels of blood cells to normal
• Kill all cells that have the Bcr-Abl cancer gene.

In the accelerated phase or blast phase, the goal of CML treatment is to

• Kill all cells that have the Bcr-Abl cancer gene or
• Return the disease to the chronic phase.

It is important to receive treatment in a center where doctors are experienced in the care of patients with CML.

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Oral CML Therapy 

Chronic Phase CML Treatment

In chronic phase CML, treatment usually returns the level of blood cells to normal. The spleen returns to its normal size. Most patients don't have infections or unusual bleeding.

Most CML patients begin treatment with a drug called Gleevec. This drug has been FDA-approved since 2001. Gleevec controls chronic phase CML for most people as long as they continue to take the drug. Patients who do not respond to the usual dose of Gleevec may respond to a higher dose.

Gleevec does not help all people with CML. Another drug may be used to treat a person with CML for one of these reasons:

• Gleevec did not control the person's CML (called drug resistance"
• The person has strong side effects from Gleevec (called drug intolerance)
• Gleevec stopped working (called a loss of response).

For patients who cannot tolerate Gleevec or who have CML that is resistant to Gleevec, there are two newer FDA-approved drugs called Sprycel and Tasigna. Sprycel is approved to treat adults in all phases in all phases of CML with resistance or intolerance to prior therapy including Gleevec. Tasigna is approved to treat chronic and accelerated phases of CML in adults who are resistant or intolerant to prior therapy that included Gleevec. All three drugs, Gleevec, Sprycel and Tasigna are taken by mouth.

Most patients being treated for chronic phase CML can go about their day-to-day activities. With drug treatment most patients are symptom free for very long periods (called a remission). However, patients are not cured of CML with drug treatment. They are checked carefully for any signs that CML is returning (called a relapse). They will need regular health check-ups, including blood tests. From time to time patients will need a bone marrow test.

Accelerated Phase or Blast Crisis Phase Treatment

The goal in treating accelerated or blast crisis phase CML is to kill all cells that contain the Bcr-Abl gene or to return the patient's disease to the chronic phase.

Gleevec, and for certain patients, Sprycel or Tasigna, is an effective treatment for people who have accelerated or blast crisis phase CML. Other drugs—such as interferon, busulfan (Myleran®), cytarabine (Cytosar-U®) or hydroxyurea (Hydrea®)—may be used with those CML oral drugs.

Some people with CML have very high white cell counts at the time of diagnosis. This can reduce blood flow to the brain, lungs, eyes and other parts of the body. Hydrea may be used to decrease the white cell count. After the white cell count drops, oral drug therapy can be started.

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Stem Cell Transplantation

Stem cell transplantation is another important treatment for certain CML patients. Allogeneic stem cell transplantation is the only curative treatment for CML. It is a treatment to restore a person's marrow. The transplanted stem cells go from the person's blood to his or her marrow. The cells start a new supply of red cells, white cells and platelets. The person needs to have a "matched" stem cell donor for the transplant. The donor can be a sibling or another person with stem cells that "match" the stem cells of the transplant patient.

About 7 out of 10 people who have an allogeneic transplant are cured of their CML. But this procedure has a high risk of serious complications. This treatment is most successful in younger patients. It may be considered for people up to about 60 years of age who have a matched donor and who do not have a good response to oral drug treatment. The decision to do a transplant for CML patients depends on:

• The patient's age
• The patient's overall health
• How well the donor cells and the patient cells match
• The degree of the patient's response to oral drug therapy

If a stem cell transplant is suggested for you, your doctor will discuss the benefits versus the risks of having this treatment. Doctors are studying a type of stem cell transplant called a reduced-intensity transplant (nonmyeloablative stem cell transplant). It may be helpful for older patients who are not eligible for allogeneic stem cell transplantation.

Donor Lymphocyte Infusion

CML patients whose disease returns after an allogeneic stem cell transplant (called a relapse) may be treated with Gleevec, Sprycel, Tasigna or other CML drugs. Another treatment choice is a second transplant. Or patients may be treated with a donor lymphocyte infusion (an infusion of white cells called lymphocytes from the original stem cell donor).

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Clinical Trials

Clinical trials are used to study new drugs and new combinations of drugs, new treatments or new uses for approved drugs or treatments. There are CML clinical trials for people of all ages.

Some clinical trials test new ways to use drugs that are already approved. For example, changing the amount of the drug or giving the drug along with another type of treatment might be more effective. Some clinical trials combine drugs for CML in new sequences or doses.

• Ongoing studies are comparing Gleevec to Sprycel (or Tasigna) for newly diagnosed individuals. Study data will help in identifying which patients are least likely to respond, or most likely to lose a response, to Gleevec therapy.
  
• New drugs are being studied for people with CML that does not respond to Gleevec, Sprycel or Tasigna.

Vaccine Therapy

 Various forms of vaccine therapy are being studied. It is possible that one day vaccines will be able to treat (not prevent) the disease by using a person's own immune cells to attack his or her CML cells.

Reduced-Intensity Transplant

 Doctors are working to make allogeneic stem cell transplants safer. A type of transplant called a reduced-intensity transplant is under study in clinical trials. A reduced-intensity transplant uses a lower dose of conditioning chemotherapy than the dose used with a standard allogeneic stem cell transplant. This treatment is also called a nonmyeloablative transplant. Older and sicker patients may be helped by this treatment.

Ask your doctor if treatment in a clinical trial is right for you. You can also call the Information Resource Center for information about clinical trials or use the LLS-supported, free clinical trials service TrialCheck®.

See the free LLS publications The CML Guide. Information for Patients and Caregivers and Chronic Myelogenous Leukemia for more details about clinical trials.

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Tracking Treatment Response

Measuring treatment response is very important. Blood and marrow tests are used to track a person's level of response to treatment. The results are used to help the doctor decide if the person's CML is well controlled or if there is a need to 

• Increase the dose to try for a better response
• Decrease or stop the drug briefly because of side effects
• Change to a different drug or combination of drugs to better control the CML
• Change to a different drug or combination of drugs to manage side effects.

General Guidelines

 There are general treatment response guidelines for the first year of CML drug therapy. But keep in mind that people with CML respond to treatment in different ways. Blood tests and/or bone marrow tests may be used to determine the level of CML drug therapy response.

A person's response is measured against his or her lab test results at the start of treatment. The number of red cells, white cells, platelets and CML cells is measured on a regular basis throughout treatment.

• After diagnosis, marrow testing is usually repeated at 6 and 12 months within the first year of diagnosis.
• Many doctors do bone marrow testing one to two times a year in the second year after diagnosis.
• Doctors may repeat the bone marrow tests every 12 to 18 months once a good response is achieved.

 Your doctor may use the terms hematologic, cytogenetic or molecular response (remission).

Hematologic Response - A complete hematologic response means that the numbers of white cells, red cells and platelets are normal or near normal. A complete blood count is done to measure the numbers of white cells, red cells and platelets, and the levels of hemoglobin (a protein in red cells that carries oxygen) and hematocrit (the amount of blood that has red cells).

Cytogenetic Response - A complete cytogenetic response means that there are no cells that can be detected with the Ph chromosome and the Bcr-Abl cancer gene. The FISH test is done to measure the number of cells with the Ph chromosome and the Bcr-Abl cancer gene.

Molecular Response - A partial molecular response means that there is a reduction in the number of cells with the Bcr-Abl cancer gene. A major molecular response means that there is a 1,000-fold decrease in the level of cells with the Bcr-Abl gene from the level measured at the start of treatment. A complete molecular response means that the Bcr-Abl cancer gene cannot be detected by PCR. Remaining CML cells that cannot be detected by PCR are called "minimal residual disease." PCR is done to measure the number of cells with the Bcr-Abl cancer gene. The same laboratory should be used each time for PCR testing if possible. This is because results may vary from lab to lab.

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CML-Related Disorders

The name chronic myelogenous leukemia is sometimes used for other types of myelogenous leukemia that have a chronic course. Chronic myelomonocytic leukemia (CMML), juvenile myelomonocytic leukemia (JMML) and chronic neutrophilic leukemia (CNL) have some of the signs and symptoms of CML.

These diseases are less common myeloproliferative diseases that are subtypes of myelogenous leukemia and progress more slowly than acute myelogenous leukemia. People with these diseases do not have the Bcr-Abl gene; this is one of several distinguishing features used to make a diagnosis.  These patients are not expected to (and have been proven not to) respond to treatment with Gleevec.

For more information on these types of CML, see the free LLS fact sheet, Chronic Myelomonocytic Leukemia (CMML) and Juvenile Myelomonocytic Leukemia.

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Questions for the CML Specialist

It is important to choose a doctor who specializes in treating CML and knows about the most up-to-date treatments. This type of specialist is usually called a hematology oncologist. Or, your local cancer specialist can work with a CML specialist.

You can talk with your doctor about how he or she plans to treat your CML. This will help you to be actively involved in your care and to make decisions. It may be helpful to write down questions to ask your doctor. Then, you can write down your doctor's answers and review them later. You may want to bring a family member or friend with you to the doctor. This person can listen, take notes and offer support. Some patients like to record information from the doctor and listen to it at home.

Click here for the CML drug therapy question guide. 

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Get More Information

Further details of treatment and supportive care and the beneficial and adverse effects of treatment may be obtained from the free LLS publications The CML Guide. Information for Patients and Caregivers and Chronic Myelogenous Leukemia.

Measuring your CML treatment response is important. My CML Tracker is an online tool to help you keep track of appointments, questions for your doctor, medications, side effects, test results and notes.

LLS also offers education programs featuring leading leukemia specialists discussing the latest issues in the diagnosis and treatment of leukemia. 

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Contact Us

The Leukemia & Lymphoma Society
1311 Mamaroneck Ave.
White Plains, NY 10605

or call the Information Resource Center at (800) 955-4572.

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