Response/Remission
Hematological Response is a normalization of the blood counts, particularly white blood cell counts. This is the first noticeable indicator that treatment is beginning to work, though not necessarily in the bone marrow. The response can be partial HR(reduction in white cells,but not down to normal range) or complete CHR (white blood count at or below approximately 12,000 white cells/microliter).
Your doctor will anticipate CHR within the first three months of treatment, however, some patients may take longer to achieve this level. During the early stages of treatment, your physician will monitor you closely to keep track of the response and determine if the correct course of treatment is in place. The majority of patients easily achieve this milestone on or before the three month mark.
For detailed monitoring information see Monitoring & Tests
Cytogenetic Response (CR) is a response to treatment of CML that occurs in the marrow, rather than just in the blood.
There are 3 levels of cytogenetic response:
1) Cytogenetic response (CR or CyR): A cytogenetic response means any Ph+ chromosome reading less than what you began with at diagnosis;
2) Major cytogenetic response (MCR or MCyR); Major means 35% or less of the cells in your marrow test positive for the Philadelphia chromosome, but more than 0%;
3) Complete cytogenetic response (CCR or CCyR): Complete cytogenetic response means no Ph+ cells can be measured by either conventional or FISH cytogenetic testing (though the PCR test may still be positive).
Molecular Response (MR) is defined as a negative PCR or other negative molecular test. Molecular responses can only be measured using a Polymerase Chain Reaction/PCR test. A PCR test is defined as a very sensitive test which can be used to detect the presence of very low levels of specific genetic material (DNA). It is used to detect, and sometimes to quantify, bcr-abl in bone marrow cells of patients with CML. The most sensitive PCR tests can detect as few as one in 100,000 cells. For an explanation of how PCR works, see http://www.scientific.org/tutorials/articles/riley/riley.html
A major molecular response (MMR) means that the amount of BCR-ABL protein in your marrow is very low.
A complete molecular response (CMR), formerly (and sometimes still) referred to as PCRU means that no BCR-ABL protein is detectable in the marrow utilizing the Polymerase Chain Reaction test.
Today, the use of "PCRU" (polymerase chain reaction test undetectable, or "Philadelphia ChRomosome Undetectableas," a term coined by Dr.Brian Druker) an indicator of deepest response is changing. With the increased International Scale (IS) sensitivity of PCR testing equipment, molecular responses are "graded" as MR3.5, MR4.0, and MR4.5. In labs that are not testing at IS, the equipment is only able to detect up to a 3.5 log reduction. IS labs use equipment that is capable of higher sensitivities up to 4.0 and 4.5 log reductions. While the majority of U.S. labs are on the International Scale, if your tests are done in a lab that is NOT International Scale and your next labs are in a International Scale lab, it is possible that you will be detectable at the higher sensitivities.
When discussing the disease with fellow survivors or medical teams, the word "remission" may often be replaced with the word "response," particularly when one is taking daily treatment. The reason being that remission is often times perceived in the general public, or perhaps thought of, as a state in which the disease has been eradicated or brought under complete control so that NO ADDITIONAL
therapy/treatment (chemotherapy, biological therapy, radiation, surgery, etc.) is necessary.
The past few years have brought some amazing developments in the treatment of CML. One such development has been the arrival of clinical trials studying Treatment Free Remission or TFR. There is hope that over time, and with long, sustained molecular responses, some patients will be able to achieve a "true" remission and not be subjected to daily treatment with Tyrosine Kinase Inhibitors (TKIs). Treatment Free Remission will be discussed in greater detail here.