Since the introduction of the drug Gleevec® and similar tyrosine kinase inhibitors, the number of patients with chronic myeloid leukemia (CML) who enter remission and stay in remission for years has increased dramatically over the past decade.
For survival statistics, click here.
Measuring Treatment Response
Your doctor needs to monitor your response to drug therapy for chronic myeloid leukemia (CML) with blood and bone marrow tests. This is a critically important part of treatment for people with CML.
Your test results help your doctor decide whether to:
- Increase your drug dose to try for a better response
- Decrease or stop the drug briefly because of side effects
- Change to a different drug or drug combination to better control the CML
- Change to a different drug or drug combination to manage side effects
Your doctor measures your response using general treatment response guidelines for your first year of CML drug therapy. He or she regularly measures the number of red cells, white cells, platelets and CML cells in your blood. Your doctor compares these numbers with the results of the lab test done at the start of your treatment.
My CML Tracker Pages is a tool to help you keep track of appointments, questions for your doctor, medications, side effects, test results and notes. You may download the PDF or order a copy of My CML Tracker Pages.
Adherence to Therapy
It is important for patients to continue taking their medication to get the best response. Unless they are following their doctor’s instructions, stopping medication or taking less than the amount prescribed can impact how well the medication works and may result in a loss of response and an unfavorable treatment outcome.
For patients with CML, adhering to treatment is associated with the probability of achieving and improving long-term outcomes, including achieving a major molecular response and improved survival. Good adherence means that a patient follows all of the doctor’s recommendations, including
- Taking the appropriate number of pills as ordered: at the right time, on the right day, every day
- Reporting any side effects so that supportive treatment can be administered.
Patients should also let their treatment team members know if there are any problems (including side effects) that make it difficult for them to take the medication as prescribed. Generally, these difficulties can be either managed or completely overcome.
Your doctor may periodically examine your bone marrow. Your schedule for bone marrow testing may look like this:
- After 3 months in patients who do not have access to a BCR-ABL PCR test
- At 12 months in patients who have not yet achieved either a complete cytogenetic response or a major molecular response
- Once a cytogenetic response is achieved, infrequently
A marrow test is recommended whenever a blood test indicates you've had a change in response to oral drug therapy.
The International Scale (IS) defines the standard baseline as BCR-ABL 100% (IS). This level was arrived at by averaging the number of BCR-ABL gene molecules from 30 newly diagnosed chronic phase CML patients. Reductions in the level of BCR-ABL genes are reported as “log reductions” and expressed as a percentage.
- A 1-log reduction indicates that the BCR-ABL levels have decreased to 10 times below the standardized baseline. This is also written as BCR-ABL 10%. This reduction is approximately equivalent to a major cytogenetic response.
- A 2-log reduction means that BCR-ABL levels have decreased to 100 times below the standardized baseline or BCR-ABL equals 1%. This reduction is approximately equivalent to a complete cytogenetic response (CCyR).
- A 3-log reduction indicates that the BCR-ABL levels have decreased to 1,000 times below the standardized baseline or BCR-ABL equals 0.1%, which is also known as a “major molecular response” (MMR).
Types of Response
Your doctor checks your progress to look for your response in the following areas:
People with CML respond to treatment in different ways. These are general guidelines for CML drug therapy. Your baseline results (your test levels at the time of diagnosis) can influence your response. But, your doctor will generally work with the following time frame as a guideline to achieve the desired response:
|Period After Start of Treatment
||Optimal Treatment Milestone
Complete hematologic response (CHR)
Partial cytogenetic response (PCyR)
Continued complete hematologic response (CHR)
Partial cytogenetic response (PCyR) or better
||Complete cytogenetic response (CCyR)
||Major molecular response (MMR)
|18 months and beyond
||Stable or improving major molecular response (MMR)
BCR-ABL Gene Mutation Testing
Patients should talk to their doctor about ordering a mutation test if there is
- Failure to meet a treatment milestone
- Loss of hematologic or cytogenetic response despite taking an adequate dose of a TKI
- Unexplained confirmed rise in quantitative PCR level by a factor of 5 to10
- Concerns about the medication being effective (not working).
A mutation test does not need to be done in a patient who is switching medication as a result of side effects.
Patients should consider checking in with a CML specialist from time to time to make sure they are meeting treatment milestones. Patients can go for a consultation on their own or can ask their doctor to work in consult with a CML specialist. Patients who belong to a health maintenance organization (HMO) typically have more restrictions on their ability to seek consultation with academic medical centers. Speak to your insurance company to know what is covered under your plan.
The patient's doctor can send the patient's blood sample for BCR-ABL testing (which requires specialized equipment and expertise) to
- A reference laboratory (used for specialized tests that are ordered only occasionally or require specialized equipment)
- An academic center
- An NCI (National Cancer Institute) center laboratory.
There are commercial tests available for BCR-ABL kinase domain mutation assessment. Many employee health insurance plans require that you use a specific lab, which is often indicated on your insurance card. Sometimes, if the insurance company will not cover the test, providing clarification or justification for the testing may help your case. The National Comprehensive Cancer Network (NCCN) and the European LeukemiaNet (ELN) have suggestions for when to assess for mutations. Some insurance carriers consider mutation assessment a "genetic" test and will only authorize a single such test per lifetime. Talk to your doctor and your healthcare team to be sure that, if needed, the mutation testing will be covered by their insurance company.
For information about the CML mutation testing guidelines from the NCCN, please visit www.nccn.org.