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Understanding results of BCR-ABL Quant

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Hello my mother has CML since last 6 years, since then she is on daily dose of generic variant of Gleevec ( Ibatkin 400mg)

Untill now Quant-PCR test always showed  "Not Detected".

Test Name                                                                              Results                 Units

-----------------------------------------------------------------------------------------------------------------
BCR-ABL Gene Rearrangement, PCR Quantitative
(Real Time PCR)                                                                   Not Detected             %

 

Report for last two tests over a period of an year is showing some extra information, (although numbers mentioned in last 2 reports are exactly same)

Test Name                                                                              Results                 Units

-----------------------------------------------------------------------------------------------------------------
BCR-ABL Gene Rearrangement, PCR Quantitative
(Real Time PCR)      

P210(e13fa2, e14a2, Major) BCR-ABL rearraged copy               0

P190(e1a2, minor) BCR ABL rearranged copy number               0

ABL copy number                                                                     10693

BCR-ABL percentange ratio                                                     <0.010                      %

BCR-ABL international Scale Normalized copy number          <0.006

---------------------------------------------------------------------------------------------

 

Reference table as mentioned in the report

------------------------------------------
SIGNIFICANCE OF PERCENTAGE
------------------------------------------
% RATIO             REMARKS
------------------------------------------
<0.01                   COMPLETE MOLECULAR RESPONSE
-------------------------------------------
0.01-0.1               MAJOR MOLECULAR RESPONSE
------------------------------------------
<1%-0.1              COMPLETE CYTOGENETICS RESPONSE

 

I am unable to comprehend the report, unfortunately her oncologist didn't give much information just  that  and i quote "her BCR is increased and we might need to change her medication". 

I will be very thankful if someone can explain the change in last report, does this means she is entering into Accelerated Phase?

Thanks in advance

Karan

 

 

Karan:

You will get answers from the resident experts on this sight, but a couple of questions:

1. Were the last 2 tests done at the same lab as all the previous "not detected"?

2. If the same lab, did they change the sensitivity cutoff for the test?  Last year, my lab changed the cutoff from .01% to .003%. Some labs that have done this would have previously reported anything less than .01% as not detected.

If I read the lab report, looks to me like the detected level on the IS scale is .006%.  This is still deep molecular response and certainly not indicative of having entered into accelerated phase.  Blips like this can occur at this low a level of the PCR test and mean absolutely nothing unless future tests show a continued upward trend.  It is certainly not time to change medicine or dose.  

This happened to me a couple of months ago - I went from not detected to <.003%.  My oncologist retested me a month later and the result stayed at <.003% and I am now back on testing every 3 months.  I know this worried me at the time, but I know now that these slight variations in the PCR at low levels happen to a lot of us and are usually nothing to worry about.

Scuba will tell you that your mother will never die from CML and that is most likely correct.

 

 

I wouldn't claim to be one of the experts CMLJax refers to but I think he is most likely absolutely right about your laboratory increasing sensitivity (which is why there is more data on the report) and about the fact this result is more than good. Anything less than 0.01% International Scale is brilliant, would previously have been reported as undetectable, and from my knowledge is no reason for thinking about changing medication. For example, I am currently 7 months in to a 50% reduction in Imatinib dose (400mg==> 200mg/day), and all is going well. The protocol from the Destiny Trial in UK says I should only revert to 400mg if my PCR ABL went above 0.1%. Hope this helps.

 

I totally agree with you, Alastair. The likelihood is that it's a more sensitive test.

In any case, undetectable results always weird me out. I know I wouldn't trust the sensitivity of it and would actually prefer to see a really low (MR4.5+) result than totally undetectable unless I was very familiar with the lab setup.

I once got an undetectable - previous result 0.02, and the next result 0.02. I'm pretty certain it was a clerical error and they tested someone else blood or something like that.

In any case, Karan, your mother's result 0.006% is excellent and nothing at all to worry about. One thing that does stand out to me is that there are no actual copies of BCR-Abl shown as detected on the report. There are 10693 copies of the Abelson control gene, and unless my maths is failing me terribly, 0 over 10693 is 0, not 0.01 (or 0.006). 

For what it's worth, 10693 assays is not a high quality test. You want more than 100,000 in an ideal situation. Just 1 copy of BCR-Abl would yield 0.00935% on 10693 control genes. I think that is what has been rounded up to 0.01, but why the report says earlier there were no copies of BCR-Abl is not clear. Perhaps there was just one. And with the IS conversion, that (rounded) 0.01 has gone through a 0.6x conversion giving you that 0.006% result.

In any case, even with the slightly odd maths I would not worry one jot about that test. If I am correct with the above, it means there there was only a single cell of BCR-Abl identified in the entire test. 

David.

Hi Karen,

.... from cmljax, "Scuba will tell you that your mother will never die from CML and that is most likely correct."

Your mother will NEVER die from CML and that is correct.

Her so-called new levels are in the noise of the test. Anything below 0.01% regardless of scale is indistinguishable from PCRU or undetected. Note how they use <0.01% defined as "complete molecular response". Complete is not the same as deep.

Your mom is doing great. She will continue to do great as long as she continues to take her medication and tells you she loves you. All is good.

Whoever told her she needs to change her medication should be fired. Incompetence at work.

Hope this helps.

p.s.

The only reason she 'might' consider changing drugs is to avoid any nausea associated with Gleevec and perhaps be able to take a much lower dose of drug and avoid side effects that might otherwise be felt.

(I am PCRU and take 20 mg Sprycel - no side effects I can feel)

 

Thank you all for inputs and sharing the information.

Your responses gave us ( me & my family) a huge relief and assurance that things are under control.

@cmljax & @AlastairC

1. We always get tests done from the same lab to reduce the noise.

2. I will try to find out if lab has changed the sensitivity of the tests.

@David: Thanks for the re-assurance however I must admit my knowledge is quite limited and thus I can't get my head around the calculation you've mentioned. I will be glad if you can provide me pointers to go through to comprehend same?

May be the Note section in the report could shed some light as to how this lab computes the %.

Note
1. Sensitivity of the assay is 0.01% when copies of ABL detected is 100,000.
2. Limit of detection is 10 copies of BCR-ABL  fusion gene transripts per PCR
3. This is an in-house developed assay designed as per EAC (Europe against Cancer) protocol.
4. This test detects Major(M) gene rearrangements namely- e13a2 & e14a2 and Minor(m) gene arragement e1a2. This test
does not detect micro gene arrangement e19a2.
5. Test conducted on Whole blood/Bone Marrow.
6. This test gives % of BCR-ABL fusion gene detected with respect to the ABL transcript presennt as well
as the International scale value to harmonize the result

@Scuba: I must admit I had tears in my eyes when i read "Your mother will NEVER die from CML.."  prayers, medication, care and affection have kept us going.

 

Thanks again to all of you, can't express how much your responses helped us.

/Karan

 

 

Karan, 

To learn more about PCR tests and how they're done, results calculated and what they mean you should start with our very own PCR primer for patients. 

You can find it at this page. Just click on the icon of the booklet. 

https://www.cmlsupport.org.uk/node/20097

It is quite detailed, which is a good thing, so just read until you can't understand any more. Revisit it again later and you'll find you're able to read further as you've learned the information before. 

David

Hello 

tring to understand my results….

For 1 1/2 years results negative.  Recent Results e14a2. .1714

does anyone know what this means