About CML

Until recently the ultimate goal for CML patients treated with TKI therapy was to achieve a ‘PCR negative’ result, also known as a Complete Molecular Response (CMR). However, the use of the word ‘complete’ is now considered to be misleading because it is often interpreted to mean that there has been a total eradication of disease. Recently, international CML experts and clinical groups have agreed to stop using the term CMR replacing it with MR followed by a log reduction number, as in the definition on the next page.

Currently q-PCR is the most accurate test used to monitor response to a particular therapy and to detect any significant rise in BCR-ABL1 transcripts. Test results are used to make evidence based decisions in the context of the 2013 ELNet recommendations and NCCN Guidelines for the treatment of Ph+ CML.

Both ELNet and NCCN identify a major molecular response (MMR / MR3) within 12 months to be an optimal response and a realistic goal of
TKI therapy.

Q-PCR testing extracts the available mRNA in a blood or marrow sample. A test result is expressed as a percentage showing the ratio between of mRNA from normal control gene transcripts, for example ABL1 or BCR, compared to mRNA from the abnormal BCR-ABL1 gene transcripts present in a sample.

To perform the test, samples of blood or bone marrow are sent to the molecular pathology laboratory where mRNA is extracted from the white cells. There are a variety of ways of doing this and methods vary to a greater or lesser degree between laboratories.

What the test measures and its relationship to other tests.

At diagnosis, virtually every white cell in a blood or marrow sample will be leukaemic (Ph+) so the result should, in theory, be 100% Ph+. However, because there are higher levels of Ph+ cells present at diagnosis, q-PCR testing is not accurate, which is why Ph positivity varies between 50% and 100%. This test may be used to establish a baseline value of Ph+ cells at diagnosis.

Some sort of genetic testing will be done to look for the Philadelphia chromosome and/or the BCR-ABL1 gene. The following types of tests can confirm or deny a diagnosis of CML.

Cytogenetics: also called Karyotyping

Normally each of us inherits 23 pairs of ‘homologous’ chromosomes (twin pairs with the same basic structure) one set from our father and one set from our mother, making 46 chromosomes in total. Each pair is numbered from 1 to 22 according to size. Number 23 is the pair that defines gender, containing either an X and a Y chromosome in men, or two X chromosomes in women.
All 23 pairs are found in the nucleus or ‘engine’ of all blood cells apart from red cells.