After reaching a complete hematologic response (CHR) one could hope for a complete cytogenetic response (CCyR). This response would mean that there are no CML cells in the blood or bone marrow that can be detected by the Fluorescence In Situ Hybridization (FISH) test. FISH is a quantitative test that can identify the presence of the Bcr-Abl gene. It does this by using binding DNA agents that are specific for Abl and Bcr. The probes for both Bcr and Abl are labeled with chemicals that each release a different color of light. The color shows on the chromosome that contains the gene, normally chromosome 9 for Abl and chromosome 22 for Bcr. FISH can detect the piece of chromosome 9 that has moved to chromosome 22 in CML cells. Since FISH can detect Bcr-Abl in blood cells, it can be used to determine if there is a significant decrease in the number of circulating CML cells as a result of CML treatment. The number of cells at this stage is estimated at less than 1/100 of the level at the start of treatment. Pretty interesting stuff, if I do say so myself!
So, assuming that you have reached first complete hematologic response (CHR), and then complete cytogenetic response (CCyR), you next goal would be a major molecular response (MMolR) and finally a complete molecular response (CMolR).
A complete molecular response is achieved when the leukemia burden is reduced to 1/10,000 or less below the level at the start of treatment. In this stage there is no evidence of the Bcr-Abl RNA or DNA in the blood or the marrow. This quantitative Polymerase Chain Reaction (PCR) test is done by increasing or amplifying small amounts of specific pieces of either RNA or DNA making them easier to detect. It is the most sensitive test of all. When performing this test, the Bcr-Abl abnormality can be detected even when present in a very low number of cells. About one abnormal cell in one million cells can be detected by PCR testing.
This complete molecular response is the ultimate goal of all people that are diagnosed with chronic myelogenous leukemia. Unfortunately this goal is not always an easy one to achieve. It requires diligently taking a Bcr-Abl tyrosine kinase inhibitor every day. These TKI’s come with a long list of side effects and risks. The greatest risk (in my unprofessional opinion, besides death from a heart attack of course) is becoming intolerant to the drugs and thus needing a bone marrow transplant in order to live. So with CMolR in sight, I march forward in my battle to reach this goal!