Doctors use molecular responses to monitor the effectiveness of CML treatment. A major molecular response is when the amount of the abnormal BCR–ABL gene in your blood and bone marrow is lowered to 0.1% of your baseline measurement.
Chronic myeloid leukemia (CML) makes up about
Nowadays, about 85% of people with CML live at least 10 years, and the average life expectancy is nearly as long as for people without CML.
Molecular response is one of the ways that doctors monitor the effectiveness of your CML treatment. It’s a measure of how many cells in your blood and bone marrow carry the BCR–ABL gene.A major molecular response is when the amount of this gene is lowered
Read on to learn about molecular responses to CML treatment and how doctors use these responses to monitor the effectiveness of treatment.
Doctors monitor how well your CML treatment is working by using blood and bone marrow tests to monitor
- Hematologic response: A hematologic response is a measure of how many cells in your blood look abnormal under a microscope. This response is achieved when:
- Your white blood cell count is less than 10,000 per microliter (µL) of blood.
- Your platelet count is less than 450,000 per µL of blood.
- You have less than 5%
basophilsin your peripheral blood.
- There are no circulating immature myeloid cells in your peripheral blood.
- Your spleen is back to a normal size (not palpable).
- Cytogenetic response: A cytogenetic response is a measure of how many cells in your bone marrow have a genetic abnormality called the Philadelphia chromosome. A complete cytogenetic response is when there are no Philadelphia chromosome cells detectable.
- Molecular response: A molecular response is a measure of how many of your cells in your blood and bone marrow contain the BCR–ABL gene. It’s measured with a polymerase chain reaction (PCR) test in a laboratory using a sample of either blood or bone marrow cells. A major molecular response is noted when there’s a 1,000 times decrease in the BCR–ABL gene cells from the baseline (pretreatment) measurement.
BCR–ABL forms when the BCR gene that’s normally found on
According to the
Measuring levels of BCR–ABL in your blood with a PCR test is an important way of judging your treatment’s effectiveness. Reaching a major molecular response shows doctors that your treatment is lowering the number of cancerous cells in your body.
An older 2011 study found that people with CML who achieved an early major molecular response were more likely to experience a lasting cytogenetic response and lower rates of disease progression.
If doctors don’t see your BCR–ABL levels dropping over time, they may want to change your treatment.
Doctors consider both how much and how quickly BCR–ABL levels drop when judging how well your treatment is working.
The National Comprehensive Cancer Network (NCCN) lists the following thresholds as optimal or warning responses:
|Optimal response (BCR–ABL percentage compared with baseline)
|Warning response (BCR–ABL percentage compared with baseline)
|Equal to or less than 10%
|More than 10%
|Equal to or less than 10%
|Less than 1%
|Any time after 12 months
|Less than 0.1% (major molecular response)
The NCCN considers a response of greater than 10% at months 6 and 12, or greater than 1% any time after 12 months, to be a treatment failure. If you have a treatment failure, doctors will likely want to try a different combination of medications.
Other expert groups, such as the European Society of Medical Oncology, have slightly different guidelines about how quickly BCR–ABL levels should drop for optimal results.
When you first receive a diagnosis of CML, a doctor will want to perform blood and bone marrow tests. You’ll repeat these tests at least every
Doctors can determine your molecular response by using a PCR test to identify BCR–ABL by taking either a sample of your blood or bone marrow.
Doctors can take a sample of your bone marrow using a long, thin needle. This procedure is called a bone marrow biopsy. They can receive a sample of your blood through a vein in your arm.
A major molecular response is sometimes also called major molecular remission. The term remission means that the signs of your cancer are reduced.
Treatment-free remission is another term a doctor might use. It’s defined as keeping a major molecular response even after you stop taking TKIs.
A doctor may tell you that you have a complete molecular response if your BCR–ABL levels are below 0.0032% from your pretreatment baseline. You may be a candidate for discontinuing TKIs if you achieve a complete molecular response.
Research suggests that people who have a fast response to CML treatment, within
A deep molecular response is a prerequisite for a trial of discontinuing TKIs.
Your molecular response to CML treatment is a measurement of how many cells in your blood or bone marrow contain the abnormal BCR–ABL gene. A major molecular response is when levels of this gene are 1,000 times lower than your pretreatment baseline measurement.
The majority of people with CML achieve a major molecular response. However, if you don’t achieve this milestone after 12 months, a doctor may want to switch your treatment.