Should a Kinase Mutation Test be obtained ONLY at bcr/abl levels above 0.1%, or should it also be obtained at levels BELOW 0.1%, if there have been 3 consecutive significant increases in the values ? Is a significant increase a one log increase? The values bounce around so much at low levels, it is difficult to know when to be concerned. Thanks, Frank
Kinase Mutation Test
Posted 18 October 2011 - 09:18 AM
Posted 18 October 2011 - 11:23 AM
A Kinase Mutation Test is not sensitve enough to detect below approximately CCyR levels.
The 1 log increase rule does not apply unless the person also loses CCyR. So it does not apply to 1 log increases at or around MMR levels.
Posted 19 October 2011 - 06:36 PM
This question is great timing for us. Kayne has just received his best results so far: blood 0.017 and bone marrow 0.036. Unfortunately though, his oncologist said that the (cytogenics? or FISH) checked 300 cells and found 2 with the philadelphia chromosone. That seems wrong to me though with the low PCR results, is my understanding correct?
Anyway, she mentioned that she would like to see if he is still sensitive to Dasatinib but the blood test asks for
20ml perph blood in EDTA"
Would I be getting this for nothing (Kayne is 5 years old and doesn't particulary like blood tests).
Posted 19 October 2011 - 10:58 PM
The FISH could easily be false positives. The test is done by color, and the colors can be distorted on the test at the 1 - 2% level.
I would think the mutation test is a waste of time and kid-patience.
Tell Kayne we think he is doing great, and that we admire his courage....and that he has a great Mom.
Posted 20 October 2011 - 12:33 AM
Posted 20 October 2011 - 06:45 AM
Michelle, that is wonderful news about Kayne's results - I'm so glad for you both Pinichio xxx.
Diagnosed 9 June 2011, Glivec 400mg June 2011-July 2017, Tasigna 600mg July 2017-present (switched due to intolerable side effects, and desire for future cessation attempt).
Commenced monthly testing when MR4.0 lost during 2012.
2017: <0.01, <0.01, 0.005 (200mg Glivec, Adelaide) <0.01, 0.001 (new test sensitivity)
2016: <0.01, <0.01, PCRU, 0.002 (Adelaide)
2015: <0.01, <0.01, <0.01, 0.013
2014: PCRU, <0.01, <0.01, <0.01, <0.01
2013: 0.01, 0.014, 0.016, 0.026, 0.041, <0.01, <0.01
2012: <0.01, <0.01, 0.013, 0.032, 0.021
2011: 38.00, 12.00, 0.14
Posted 27 October 2011 - 04:10 AM
Therefore, if there are 3 consecutive 1 log increases in bcr/abl at levels BELOW 0.1%, one would not obtain a Kinase Mutation test until the 0.1% level is teached. However, should anything else be done, other than waiting? Thanks, Frank
Posted 27 October 2011 - 04:27 PM
If it were me, I would increase the dosage a bit.
Posted 03 November 2011 - 06:45 AM
I wanted to understand if there are any mutations that are resistant to all three - Imatinib, nilotinib and dasatinib ?
i am concerned because my mother's PCR report is on 12 % at 12 months same as 12 % done 5 months ago.
Does this mean there is resistance ? although her pcr decreased from 17% (test done in jan '11) to 12 %(test done in may'11).
I have posted my concern before also and you all were kind enough to give me your point of view. However yesterday when i visited her onc, she informed me if the disease were to stay for long in the body then it is more likely to develop resistance to imatinib .. is this true ? also if the body develops resistance to imatinib , will the second generation drugs work ?
Diagnosed in Sep'10, Gleevac started on 28th Sep '10
PCR in Jan '11 - 17% (400mg Gleevac)
PCR in May'11 - 12.35% (dosage increased to 500 mg)
PCR in Oct'11 - 12.5 % (dosage increased to 600 mg)
PLease help me get some clarity ..
Posted 03 November 2011 - 08:49 AM
There may not have been enough time for the increased dosage of 600mg to show up in the recent PCR. Since there is not an increase in the PCR, there is no sign of drug resistance. But she is not responding very quickly. If the other drugs were an option for her, that would be a good idea. But since Gleevec is the available drug, there are a couple choices: 1) stay on 600mg and see what the next PCR shows (should be done within 2 months), or 2) increase dosage to 800mg (maximum dosage). Some people require 800mg to do well on Gleevec.
You asked about what her Onc said:
"the disease were to stay for long in the body then it is more likely to develop resistance to imatinib"
That is not the right way to view the issue. Actually, the longer it takes to get the CML under control, the more likely that there is an underlying problem that could include drug resistance. So it is a matter of resistance showing up over time, rather than resistance developing. But it is accurate that left untreated, CML will gain advantages over time.
There is one kinase mutations (T315i) which is resistant to all 3 drugs. There are other kinase mutations which are resistant to one or more drugs, but not all three. Her PCR does not clearly show a kinase mutation at this point.
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