Monitoring and Tests
A variety of tests are used to diagnose, determine disease phase, and monitor your CML. You will often times hear these tests identified by an acronym. We have defined the acronyms and tests below:
CBC or Complete Blood Count - a blood test that measures the proportions and total number of white blood cells, red blood cells, and platelets. It also gives information concerning the shape, size and variation of these cells. In CML a “white cell differential” is usually performed along with the CBC. This tells which of several kinds of white cells are present, and in what proportion.
BMA or Bone Marrow Aspiration - a procedure in which liquid contents of a patient’s bone marrow are withdrawn (aspirated) through a needle. This procedure is used to make the diagnosis and to follow the progress of treatment of CML.
BMB or Bone Marrow Biopsy - similar to a bone marrow aspiration, but used less frequently and performed with slightly different equipment. It is used when a larger or different kind of sample of marrow is needed, or when a BMA is unsuccessful because the marrow is too fibrous to permit aspiration through the BMA needle.
Karyotyping - A cytogenetic test to identify chromosomal abnormalities as the cause of a disease. This test looks at a small number of cells (about 20). For more about karyotyping, see: https://medlineplus.gov/ency/article/003935.htm
FISH or Florescence In Situ Hybridization - a cytogenetic test that is used to reveal the presence of the “bcr-abl” gene. The abl DNA shows up as a red dot in the microscope slide and bcr DNA shows as a green dot. In the nuclei of normal cells, where abl and bcr are on different chromosomes, these dots appear separately. But in Ph+ leukemic cells where bcr and abl are fused, the dots appear together. If you see RedGreen the cell is Ph+, while Red-------Green (that is, they’re far apart) is Ph-, normal.
(See http://en.wikipedia.org/wiki/Fluorescent_in_situ_hybridization for a representative photo).
PCR or Polymerase Chain Reaction - 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 1,000,000 cells.
Learn more about PCR at our partnering site: MY PCR
(See http://www.scientific.org/tutorials/articles/riley/riley.html for an explanation of how PCR works.)
It is also important that a frequent and consistent monitoring schedule be in place, particularly during the first 18 months following diagnosis, or until you have achieved a satisfactory level of response. The following guidelines are recommended by the NCCN and European LeukemiaNet and followed by leading CML Specialists in the United States and around the globe, respectively.
Response LevelDefinitionMonitoring Frequency/Schedule
Complete Hematologic Response (CHR)
A hematologic response (HR) is one that happens with blood counts. For example, when diagnosed your white count may have been quite high. A positive hematologic response would be indicated by a decrease in your white count. For practical purposes, a HR means that your blood counts have returned to the normal range. When the counts return to the normal range, it is said that you have had a COMPLETE hematological response (CHR).
At diagnosis and then every 15 days until CHR has been achieved and confirmed, then at least every 3 months or as required.
A cytogenetic response is indicated by the number (or percentage) of Philadelphia Chromosome positive (PH+) cells contained in the bone marrow. A complete cytogenetic response (CCyR) indicates that no PH+ metaphases are present in the sample. PCyR indicates that only 1 - 35% of the sample contains PH+ metaphases. Minor: 35 - 65%. Minimal: 66 - 95%.
During this cytogenetic test, the Cytotechnologist literally counts cells in a sample. They look at 100 cells and base the percentages on that sample. Thus, one would have acheived CCyR when no CML cells are found in the sample. PCyR when 1 - 34 cells were found, etc.
The results from this test do not suggest that there are no CML remaining - rather, it indicates the level at which the bone marrow has been cleared of CML cells. Once on has achieved CCyR, a more sensitive molecular test (RT-Q-PCR - Realtime Quantitative Polymerase Chain Reaction).
At diagnosis, 3 months, and 6 months, then every 6 months until CCyR has been achieved and confirmed. Every 12 months after confirmation of CCyRif regular molecular monitoring cannot be assured.
Complete Molecular Response (CMR)
Major Molecular Response (MMR)
A molecular response is determined using the highest level of monitoring available for the CML patient. A complete molecular responseindicates the the BCR-ABL gene (a.k.a. the Philadelphia Chromosome) is undetectable in 2 consecutive blood samples as tested via Real Time Quantitative and/or nested Polymerase Chain Reaction (PCR).
As PCR testing has become more sensitive, one may see response levels of MR4.0, MR 4.5, and MR5.0 instead of "CMR." These newer designations indicate molecular responses at 4, 4.5, and 5 logs.
A major molecular response indicates that the ratio of BCR-ABL to ABL (CML cells to normal [those not containing the Philadelphia chromosome] cells) is less than, or equal to 0.1 on the International Scale (IS). MMR is a three (3) log reduction of one's CML from baseline levels shown at diagnosis.
RT-Q-PCR: Every 3 months until MMR has been achieved and confirmed, then at least every 6 months.
Mutational analysis: In occurrences of suboptimal response or failure, should ALWAYS be required before changing to another TKI or therapy.
Note: this chart has been adapted from the 2014 NCCN and European LeukemiaNet Guidelines for CML.