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Results confusion

Hello everyone.

I wonder if anyone can help me please? I'm a bit confused about my husband's latest test results.

Until now the results have been in percentages - he was diagnosed late December last year, and his result in August was down to 4 per cent, which we thought was pretty good.

The specialist nurse has called him this morning to say his latest test was a pcr test - we thought they'd been pcr tests all along - as now the percentage is so low they need to do a more sensitive test, which makes sense.

So, apparently, from a start of 124, he's now down to 6.2, and I'm a bit unclear what that means exactly or how that equates with the percentage results he'd been getting. Is a pcr result of 6.2 better than the percentage result of 4, or has his levels increased this time?

I probably sound a bit stupid, but I've realised I haven't really understood the testing after all. 

Thanks in anticipation of your help.x

It can be very confusing so don't worry about being confused.

Most people are not tested by PCR until the amount of PH+ cells reduces to such levels that they cannot be seen or detected by FISH tests -which normally looks at around 200 cells. Initially cytogenetic tests will be used which only looks at around 20 cells.... see explanation from our FAQ page below.

So it is likely that the percentage of 4% refered to the amount of PH+ cells visible (by microscope) using the  FISH test. This test also has an error margin so is not at all precise in the way that PCR (molecular) test is. 

The new result you mention is from a PCR test so is much more accurate in the actual level of disease present.. as it is so much more sensitive... PCR shows the ratio of abnormal cells to normal cells. So the recent result of 6.2 can be veiwed as a much more accurate picture of the level of disease still present because it is looking for disease on the molecular level and will have tested far more cells. 

Your husband should now want to see fruther reductions in the ratio of white cells showing the normal gene (Abl) to cells with the abnormal gene (Bcr/Abl)- this is the abnormal gene that causes CML and is present in the PH+ white cells)... it is good news that his level of disease is now getting low enough to initiate PCR testing rather than normal cytogenetics and/or FISH.

I would say therefore that it is better to have a 6.2% by PCR than 4% by FISH, as the PCR test is the more sensitive one and tests many more cells -100,000 and upwards- on the molecular level.

What you should hope to see in future PCR results is:

A PCR result of around 1.5% (or lower) which would indicate a complete cytogenetic response (CCyR).

Any lower than 0.1% is described as a major molecular response (MMR).

I hope I have not confused you further.

Sandy

 

Bone marrow cytogenetic test

A sample of bone marrow will be taken from you. The bone marrow cells are then examined under a microscope to see how many of the abnormal cells a represent. Usually, around 20 cells are examined at a time.
 

FISH cytogenetic test

FISH (which stands for fluorescence in situ hybridisation) is another type of cytogenetic test. It can be done on either a blood sample or a bone marrow sample. After the sample has been taken from you, it is mixed with a substance that attaches itself to the Philadelphia chromosome inside your blood cells.

This substance glows – or fluoresces – when examined under the microscope. This makes it easy for the scientist to count the number of abnormal chromosomes you have in your blood. The FISH test is more sensitive than the conventional bone marrow cytogenetic test as it looks at more cells at a time.

Molecular response and tests

Molecular testing is the most sensitive type of test. It can tell if there is the slightest trace of disease remaining, even if you have achieved a complete haematological and cytogenetic response to treatment. The technique used to measure this is called polymerase chain reaction (PCR). This test will be done when you have responded to your treatment to the point that the abnormal cells cannot be seen on the bone marrow cytogenetic test.

 

An RQ-PCR test is a  blood test that measures the number of Ph+ CML cells in your blood. It is an important test to perform because it is very sensitive. It can detect 1 Ph+ CML cell out of 100,000 cells, so it can detect very low numbers of remaining Ph+ CML cells. Remember, the lower the amount of Ph+ CML cells left in the blood, the less chance there is for Ph+ CML to relapse and progress. Therefore, this test will help us know how well your treatment is working and help us make better decisions about your care.

What is a log drop?

An RQ-PCR test measures the number of Ph+ CML cells in your blood. The way it counts the decrease of cells is in terms of a log drop or log reductionEach log reduction means you have 10 times fewer BCR-ABL genes than you had at diagnosis. For example, a 1 log reduction is the same as dividing the number of Ph+ cells you have at diagnosis by 10. Ultimately, what is most important is that the trend of your log reductions continues to decrease over time until you reach a major molecular response, which is equivalent to a 3-log reduction (or 0.1% BCR-ABL to control gene (ABL) ratio on the international scale). Results from 2 landmark studies show that patients who have a major molecular response have a much better chance of remaining free from disease progression, or relapse. 

Hello Sandy

Thank you so much for your comprehensive reply - your knowledge is amazing!

Just one more question if you don't mind, can I just clarify that cytogenic remission is the same as a complete cytogenic response, which happens at a pcr result of 1.5% or less please? Other posts have mentioned cytogenic remission relating to other, higher figures, and I wondered what the difference is.

Thanks again for the info and for being so kind.x

I think there is some confusion regarding the meaning of the letter R in the context of CML tests.

We are all used the word 'remission' when talking about cancer in general and usually understand this to mean that the treatment (such as chemotherapy) has worked- but has not necessarily 'cured' the cancer. 

With CML we are used to talking about 'response' to TKI therapy and this has a different meaning for us. So the R in CCyR does not mean remission it means response. We know that the TKI drugs do not 'cure' but what they do is keep the disease under control at very very low molecular levels and we need to reach these low levels to be sure of keeping the disease at bay for the long term.

Therefore: CCyR means Complete Cytogenetic Response and to my knowledge the level of abnormal gene (bcr/abl)  should be at least as low as approximately 1.5% (preferably within 6-12 months) before it can be said you have had a Complete Cytogenetic Response. Higher figures (if they continue on a sginificant downward trend from the level at diagnosis eg. from 100% down to 65% or lower) would indicate that you have had an MCR or major cytogenetic response (rather than remission)

Watch the video posted on the video webcast page to hear Tim Hughes talk about monitoring response to therapy and the ELNet guidelines for measuring the optimal timelines for response to TKI therapy.

It is easy to see why the two words become confused.... but if you are being treated with one of the TKI's, response is the word that we need to focus on- remember, if you have an 'optimal' response to therapy- ie. a 3 log reduction in the % of bcr/abl in your marrow, then you are very likely to hold that response for the very long term. I suppose then you could say you are 'in remission' (as long as you continue to take the pills)!

Best wishes,

Sandy