There are a number of different types of treatment for CML. These include:
These are drugs that can identify and attack specific cancer cells with reduced harm to normal cells in the body. In CML, the drugs used to do this are called tyrosine kinase inhibitors (TKIs) which block certain chemicals produced by the Philadelphia chromosome. Blocking the chemical stops the cancer cells from growing and dividing.
In Canada the following TKIs are approved to treat CML*:
- Gleevec® (imatinib mesylate) and generics (Apo-imatinib, Teva-imatinib, Cobalt-imatinib)
- Sprycel® (dasatinib)
- Tasigna® (nilotinib)
- Bosulif™ (bosutinib)
- Iclusig™ (ponatinib)
*While these medications have been approved in Canada, not all provinces provide funding for their use as first-line therapies. This means that you may not have access to all of them depending on where you live. To find out which TKIs are funded in your province, click here.
Chemotherapy used to be the main treatment used for CML, until targeted therapy became available. Chemotherapy is still used, but usually after targeted therapy has stopped working.
Common chemotherapy agents used in CML are busulfan, hydroxyurea and cytarabine.
High-dose chemotherapy with donor stem cell transplant
High-dose chemotherapy is used during stem cell transplant to help replace cancer cells with the stem cells. Once the chemotherapy is complete, stem cells are infused into the patient where they grow and replace the cells that were destroyed by the chemotherapy.
Biologic therapy helps boost or direct the patient’s immune system to fight the cancer. A biologic called interferon alpha may be used when a patient cannot tolerate targeted therapy. Interferon is still used today for women who want to become pregnant or in combination with other therapies in clinical trials.
Donor lymphocyte infusion (DLI)
DLI is sometimes used after stem cell transplant. Lymphocytes, a type of white blood cell, are harvested from the donor and are given to the patient by infusion. These new white blood cells see any cancer cells as not belonging to the body and attack them.
A splenectomy is surgery to remove the spleen.
As research continues to look for ways to fight CML, new types of treatment are being tested in clinical trials. Talk to your doctor if you would like to know more about clinical trials. You can also search the U.S. National Institutes of Health clinical trial database.
What you need to know about side effects:
- All medications have the potential for side effects
- Not every person gets every side effect, and some people don’t get any
- Side effects can vary greatly from drug to drug and from person to person
- All changes and side effects should be reported to your doctor
- Talk to your doctor and nurse about:
- Which side effects are most likely with your treatment
- How long they might last
- How bad they might be
- When you should call your doctor
- What you can do to prevent them or treat them once they occur
The following table outlines some of the side effects associated with the three most commonly used treatments:
|Side effects of common CML treatments|
|Targeted therapy (TKIs)||Chemotherapy||Biologics|
|Low white blood cell counts (infections)||Here is a lot of copy and text to describe what is happening in this table||Flu-like symptoms|
|Low platelet counts (bruising, bleeding)||Here is a lot of copy and text to describe what is happening in this table||Fatigue (tiredness)|
|Fatigue (tiredness)||Nausea and vomiting||Bone pain|
|Nausea or vomiting||Low white blood cell counts (infections)||Fever|
|Diarrhea||Low platelet counts (bruising, bleeding)||Nausea|
|Heartburn||Low red blood cell counts (anemia), which can lead to feeling tired and weak||Problems with thinking and concentration|
|Muscle cramps or pain||Low blood cell counts|
|Fluid retention and swelling, especially around the eyes|
|Hypertension (high blood pressure)|
|See note below*|
|Side effects of TKIs are generally mild and can often be managed. However, rare and unusual side effects can happen with some of these drugs, and some can be serious.||Most side effects last a short time and go away once treatment is finished, but some can be permanent.|
Talk to your cancer care team about any side effects because there may be ways to lessen them. For example, drugs can be given to prevent or reduce nausea and vomiting.
|Some people may need to quit biologic treatment early because of side effects. However, with proper management, most people can tolerate this treatment. Side effects usually go away shortly after treatment ends.|
|*Note: this is not a complete list of side effects. For a full list of possible side effects of the medication you are taking, consult the consumer information section of its product monograph, or talk to your doctor.|
When taking any medication, you should be aware of the potential for drug and/or food combinations that might change the way the medication works in your body. Some combinations can increase or decrease drug levels, while some may increase side effects.
Be sure to talk your doctor, and your pharmacist about all medications you take and their potential to interact with each other and/or food.
What to avoid:
Fruit (and juices)
- Seville Orange
- St. John’s Wort
- Black Cohosh
- Cat’s Claw
- Kava Kava
- Milk Thistle
- Valerian Root
Interaction with Other Drugs
There are drugs you should not take while you are taking a medication to treat CML. It’s best to talk to your CML specialist and consult the product monograph of the CML medication you are taking. The monograph, which can be found inside the box your medication comes in, or may be wrapped around the medication bottle, will list all the other drugs which should be avoided or should not be taken at the same time as your CML medication.
Monographs for the TKIs most often used to treat CML can be found at the following links:
Apo-imatinib (imatinib mesylate)
Teva-imatinib (imatinib mesylate)
Your CML specialist knows best what drugs or foods you need to avoid when taking a medication to treat CML. Be sure to talk with your CML specialist about your medication, and let him or her know about all other drugs or herbal products you are taking.
How Do I Know My Medication is Working?
Monitoring treatment results
Patients being treated with a TKI need to have frequent blood count tests, i.e., a complete blood count (CBC), to determine whether there have been any changes in the number of certain blood cells. In the beginning, a CBC will likely be done every one or two weeks until blood counts are stable and then less frequently after that. The results of your CBC tests are your hematological response. Most people achieve a complete hematological response within three months. This is when blood counts appear to be returning to normal. It is the first sign that the treatment is working.
About three months after starting treatment you will either have your blood checked with a PCR test to measure the amount of the BCR-ABL gene or have your bone marrow checked for the Philadelphia chromosome. These tests are usually repeated every three to six months to check how the blood is responding to treatment. During this period, your doctor will be looking for a decrease in detectable abnormal cells.
Your molecular response is measured by a polymerase chain reaction (PCR) test. This is a sensitive test that can detect very low levels of BCR-ABL in the peripheral blood or the bone marrow cells.
When looking at your test results, your doctor will be looking for trends in your blood cell counts and not specific numbers to determine how you are responding to treatment.
What is PCR?
PCR is short for“polymerase chain reaction.” It is the main type of test used in CML to measure your response to treatment. It’s also used to test for other things, like viruses after a bone marrow transplant.
In CML, a PCR test is done in a lab, using a sample of your blood. The test finds the amount of genetic“blueprints” for the BCR-ABL gene that causes CML. A PCR test thus measures the residual (remaining) disease in your blood.
Why should you know your PCR?
Because your PCR number can be compared to the results from your earlier PCR tests, it helps give you an idea of how you are responding to treatment over time. Your doctor can explain how this number compares to where it should be, so it’s important to ask about it if you don’t know it.
How often should I have the test?
Most experts recommend that you should have a PCR test performed every three months during the early stages of your treatment. Once your BCR-ABL levels have begun to drop, indicating a good response to treatment, the test can be repeated every three to six months to make sure you are continuing to respond well.
What does a “log reduction” mean?
You may hear your doctor refer to “log reduction.” This means a reduction in your CML, or more specifically, a reduction in the number of Philadelphia chromosome positive (Ph+) cells.
|A log reduction of …||…means the number of CML cells in your blood is|
|1||10 times smaller|
|2||100 times smaller|
|3||1,000 times smaller|
|4||10,000 times smaller|
|5||100,000 times smaller|
Should my PCR level always be the same?
No. It’s normal for PCR levels to fluctuate a bit. The important thing is that the number of CML cells in your blood should trend downward over time. That’s why your doctor will keep track of your test results over the long term. Rising levels do need to be taken seriously, and your doctor may perform another PCR test in four to six weeks to check. But one abnormal PCR test isn’t necessarily a sign that your treatment isn’t working.
Something else you should know…
You may hear the term International Scale when it comes to measuring response. The International Scale (IS) standardizes PCR test results so that criteria defining treatment milestones are the same globally. For example, IS reporting defines PCR at diagnosis as 100% and MMR as 0.1%. When labs use different systems, it is difficult to accurately interpret changes in BCR-ABL levels. IS reporting equipment is sensitive, detecting log reductions of up to 4.5. Labs without IS testing can only detect up to 3.5. You could be undetectable with basic lab testing yet detectable with IS testing. If your lab is not using IS PCR testing, tests should be done in the same lab to reduce variations and measure changes.
Types of responses to treatment
Minor/minimal cytogenetic response
Thirty-five to 90 per cent of cells have the Philadelphia chromosome
Partial/major cytogenetic response
Less than 35 per cent of cells have the Philadelphia chromosome
Early molecular response or complete hematologic response (CHR)
- Immature CML cells are undetectable in the blood
- Blood counts have returned to normal
- Spleen has returned to normal size
- Overall, the number of CML cells has dropped to 1/10th of the level at the start of treatment (a 1 log reduction)
Complete cytogenetic response (CCyR)
The number of CML cells is now estimated at less than 1/100th, or one per cent of the level at the start of treatment (a 2 log reduction)
Major molecular response (MMR)
A very low amount (1/1000th, 0.1 per cent, or less of the level at the start of treatment) of the BCR-ABL gene is found in the blood (a 3 log reduction)
Deep molecular response (DMR)
BCR-ABL RNA can be found in the blood or marrow, but at very low levels. This is generally considered to be 1/10,000th or less the level at the start of treatment (a 4 or 4.5 log reduction). By IS testing standards, BCR-ABL levels are at or less than 0.01 per cent (4 log), at or less than 0.0032 per cent (4.5 log) or at or less than 0.001 per cent (5 log)
Every person’s CML journey is unique. Different patients respond differently to CML treatment. Each person’s treatment response is measured against the results from the beginning of treatment. These are called“baseline”results.
The table below is a general guide to how and when certain response types might be expected. Individual responses may vary.
|After 3 months of therapy||Partial cytogenetic response|
|After 6 months of therapy||Complete cytogenetic response|
|After 12 months of therapy||Major molecular response or better|
For more information on treatment response guidelines, visit European LeukemiaNet, a leukemia research network.
Note from the Canadian CML Network: All information in this section also appears in our book,“Living well with CML: Diagnosis and treatments, emotional and physical wellness, sex and intimacy and the future. What you need to know to live your best life with Chronic Myelogenous Leukemia”and has been reviewed by a medical advisory board. To order a copy, send a request with your address to email@example.com.