Measuring Treatment Response
Measuring your CML treatment response is essential to controlling your disease.
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.
Your doctor may periodically examine your bone marrow. Your schedule for bone marrow testing may look like this:
- six and 12 months within the first year of diagnosis
- once or twice a year in the second year after diagnosis
- 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.
Types of Response
Your doctor checks your progress to look for your response in the following areas:
Hematologic response. Your doctor tests your blood for a complete blood count 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). A complete hematologic response means that immature CML cells are eliminated from detection in the blood, the white cell count is no longer elevated, the platelet count is at or near normal values (no longer elevated) and spleen enlargement is resolved. Overall, the number of CML cells is usually decreased to one-tenth of the level at the start of treatment.
Cytogenetic response. You'll undergo a bone marrow test to retrieve the cells that need to be examined. A fluorescence in situ hybridization (FISH) lab test measures the number of cells that have the Philadelphia (Ph) chromosome and the Bcr-Abl oncogene. A complete cytogenetic response means that there are no CML cells (measured numbers of cells with the Philadelphia chromosome and the BCR-ABL cancer gene) in the blood or marrow that can be detected by FISH testing. The number of CML cells is now estimated at less than 1/100 of the level at the start of treatment.
Molecular response. Your blood and bone marrow cells are examined to measure the number of cells with the Bcr-Abl oncogenes using the extra sensitive polymerase chain reaction (PCR) test. Your doctor looks for one of three responses:
- A partial molecular response means the number of cells with the Bcr-Abl oncogene has decreased.
- A major molecular response means that quantitative PCR testing reveals a "3-log" or greater reduction in BCR-ABL RNA or DNA in the blood or marrow. A 3-log reduction is a 1/1,000 or 1,000-fold reduction of the level at the start of treatment.
- A complete molecular response means that quantitative PCR testing reveals no evidence of the BCR-ABL RNA or DNA in the blood or marrow. This is generally considered to be a reduction in leukemia burden to 1/10,000 or less below the level at the start of treatment. The remaining CML cells that PCR can't detect are called minimal residual disease. Make sure your doctor uses the same laboratory each time for PCR testing since results can vary from lab to lab.
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:
|After 3 to 6 months of therapy||A complete hematologic response and some cytogenetic improvement|
|After 6 to 12 months of therapy||A partial cytogenetic response of two-thirds reduction in the number of Ph chromosomes in the marrow|
|After 12 to 18 months of therapy||A complete cytogenetic response and partial molecular response|
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 Gleevec (at least 300 mg)
- Unexplained confirmed rise in quantitative PCR level by a factor of 5 to10
- Concerns about the medication being effective (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 HMOs 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 or 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.
For information about the CML mutation testing guidelines from the NCCN, please visit www.nccn.org.