How Do You Know If Treatment for Chronic Myeloid Leukemia (CML) Is Working?

If you are being treated for chronic myeloid leukemia (CML), you will have regular check-ups with your cancer care team to see how well the CML is responding to treatment with drugs called tyrosine kinase inhibitors (TKIs).

These checkups will happen at least every 3 months for the first year of treatment. They may continue throughout your life. If the CML isn’t responding, you may need to switch to another TKI.

During these visits, your cancer care team will examine you, check your blood counts, and may do other tests like bone marrow biopsies and lab tests of blood and/or bone marrow samples. (These tests are discussed in Tests for Chronic Myeloid Leukemia.)

In general, the sooner the CML responds to treatment and the deeper the response, the better a person’s outlook.

Types of responses to treatment in CML

Doctors look for different kinds of responses to treatment:

• Hematologic response
• Cytogenetic response
• Molecular response

Hematologic response

Hematologic response is most useful in checking if treatment is starting to work. Of the three types of responses, it’s also the simplest to check.

It is based mainly on whether the numbers of cells in your blood have returned to normal. The main test used to measure this is a complete blood count (CBC). It's done on a sample of blood taken from your arm.

A complete hematologic response (CHR) means:

• Your white blood cell and platelet counts have returned to normal
• There are no immature cells seen in your blood
• You have no signs or symptoms of the disease. This includes your spleen being back to a normal size.

Cytogenetic response

Cytogenetic response offers a deeper look at how well treatment is working against the leukemia cells.

It is based on the percentage of cells in a sample of your bone marrow that have the Philadelphia chromosome. If they have this chromosome, they are CML cells.

This can be measured with either cytogenetics or FISH testing. Both of these tests can find altered (mutated) chromosomes.

Major cytogenetic response

A major cytogenetic response means no more than 35% of cells in the bone marrow have the Philadelphia chromosome. A major response can be either complete or partial:

• A complete cytogenetic response means no cells in the bone marrow have the Philadelphia chromosome.
• A partial cytogenetic response means between 1% and 35% of cells in the bone marrow still have the Philadelphia chromosome.

Minor cytogenetic response

• A minor cytogenetic response means that 36% to 65% of the cells in the bone marrow still have the Philadelphia chromosome.

Molecular response

Molecular response is the most sensitive measure of how well treatment is working over time.

It is based on how much of the BCR::ABL1 gene (found in CML cells) can be detected by the quantitative PCR (qPCR) test.

This test is usually done on a sample of blood, but it can also be done on bone marrow.

The results are reported using the International Scale (IS), as a percentage of the level of BCR::ABL1 compared to when you were first diagnosed. How long it takes to get the response might also be factored in.

• An early molecular response (EMR) means that the BCR::ABL1 level is no more than 10% (1/10^th) at 3 and 6 months after starting treatment.
• A major molecular response (MMR) means that the BCR::ABL1 level is no more than 0.1% (1/1000^th) of what it was when you were first diagnosed.
• A deep molecular response (DMR) means that the BCR::ABL1 level is no more than 0.01% (1/10,000^th). This is also sometimes described as undetectable BCR::ABL1.

You may hear the terms long-term deep molecular response or stable molecular response. This is a long-lasting deep molecular response. It's the goal of CML treatment.