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Advice on reaching CMR

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Hi. 

So I am just over 3 month into my CML treatment  taking 400 mg imatanib daily. 

I am just awaiting any day now my latest bone marrow genetic results re PCR etc. On this journey all my bloods have shown a complete response to the treatment and are in normal levels. At my last consultation last week my DR said he was looking for a compete response re my PCR and if this is not the case he was considering increasing the Glivec or change for a second generation drug.  

Either of these options fill me with dread re the side effects which have taken 3 months to settle and me to adapt.  

My question is having read previous threads is that is it too early to expect CMR and surely a significant decrease or MMR would be normal given the timeframe? 

As soon as the results are in then I want to make an informed decision rather than just accept his view ! 

 

Mark 

 Hello Mark

I am 15 months post diagnosis now and on imatinib.

My consultant maintains that in the early days, Ph+ (Fish) trumps BCR-ABL1. She tells me that downward trend is far more important than achieving the absolute ELN targets. Expressions used such as "warning" can be worrying.  This approach was borne out by a recent Professor Steve O'Brien presentation to patients in Manchester.

For my part, I appear to be a slow responder. According to ELN, a Ph+ (Fish) of zero, a CCyR, should be achieved at six months. I achieved mine at 11 months.

My last BCR-ABL1 result is 0.5% and I am on a plateau. Unless, a downward trend recommences then I will be move to dasatinib.

To control bowel related side effects, my consultant suggested taking Loperamide along side imatinib. This has been very helpful. This leaves cramp as a primary side effect that is becoming severe. I got stuck on Monday in a swimming pool and it took me fifteen minutes to work my way out while I experienced about 20 cramp spasms in each calf.

I am told that each patient must be treated differently and age and any current ailments must be considered when considering TKI choices.

Thanks Nimbus I appreciate your response and support of my questions. 

I wish you all the best on this journey as well.  

I’m with you and the cramps and leg and joint pains are a bitch at times and one of the reasons I hope I do not have to up my medication. 

Thanks 

Mark 

Hi Mark ,welcome to the club.I am nearly 2 years in not quite undetected yet it takes time we all have our own speed ,and not an expert but learning a lot from the wonderful people on here .Your Doctor seems to be in a hell of a rush Obviously not a CML specialist ,you are only 3 months in ,your body still adjusting at the moment .Talking about upping your dose or changing TKI is far too early in my opinion anyway ,but the experts on here will tell you more I am sure .Check out all the supplements we are advised to take it costs a few bob but they help,vit d3,vit k2 ,magnesium for cramps ,turmeric,selenium, vit b12 ,fish oil ,we all rattle .Hope you are feeling ok ,don't be bullied into anything by your doctor some of them don't know much so ask as many questions as you like on here someone will always answer you .Take care ,Denise.

Hi Mark:

It is way too early for you to consider either a change in dose or a change in TKI.  The NCCN guidelines call for MMR (PCR at or better than .1% IS) by 12th month of treatment.  As long as you are trending towards that between now and then, stay the course. This site is full of fast, medium and slow responders, but most all get there and you will too.  Very few reach CMR within 3 months or even 12 months for that matter.  Your goal for now should be MMR within 12 months - if you beat that great.  Good luck

Mark, I'm wondering if this is a semantic mistake.  No onc - let alone a hem onc - would ever expect CMR at 3 months!  It's quite possible (if he used the word "complete") he is hoping for CCyR, which is Complete Cytogenetic Response (or zero on a FISH test).  Just ask him to repeat and explain what he meant.  I forget what the NCCN and ELN guidelines are at the moment, but I think you want CCyR by about 6 months.  You usually have reached that when your PCR is about 1% IS.  Reaching that used to be (perhaps still is) the so-called Gold Standard for ensuring that your CML will not progress, but I think most people these days feel that MMR (a PCR of 0.1% IS) is even better.  Post back when you have had your results and explanation.

Hi Kat 

Indeed it maybe semantic and I will certainly clarify.  Having had 3 ok ish months on imatanib and have adjusted to the usual side effects it was a concern and gave me a bit of a wobble ! 

At my review last week we were both expecting the results back from the bone marrow test in Oct. 

As they weren’t back he went though the scenarios of the up and coming results and this is where he mentioned that if it wasn’t “complete” then I would be called back this week to look at changing the meds or increasing the dose. 

Either way I will know in the next couple of days and be prepared to question around expectations 

Many thanks for the response 

 

mark 

Mark 

Hi Mark,

What are your lab results in terms of PCR and FISH?

Reporting your actual lab results here can better inform us on what you should expect.

FISH is reported as a percentage of cells under the microscope that are CML cells. It is expressed as a percentage.

PCR is a molecular measure of the protein produced by CML cells and is also a percentage in comparison to a control gene. This percentage can be above 100% if your CML is "more active" than control groups. Mine, for example, was 155% at diagnosis. FISH is usually 100% at diagnosis.

 

Hi 

I’m not local to home at the moment but from memory the PCR was 38%. I am not sure if the FISH test ? I had a BCR Abl test from bloods at the start of my diagnosis which seems to take up to 4 weeks to process.  I then followed this up within a couple of weeks with the same test on bone marrow if this makes sense !

3 months later I did a repeat bone marrow of which I am awaiting the results and triggered this thread. 

My last bloods  

127 red
4.2 wbc
Plt 133
N 3.15

When you have your labs in front of you, report what it says regarding "bcr-abl" (PCR) and/or FISH. Your CBC blood counts look fine (which is why you are not "sick").

During initial treatment, FISH is most important and the best indicator for progression free survival. FISH will usually fall to zero within the first 12-18 months. For some, faster and for some, slower. If FISH falls to zero within this time, survival exceeds 95%. The other 5% die for other reasons - so in other words, reaching zero FISH one has beat the disease despite having to continue treatment.

PCR is the canary in the 'mine shaft' in that it measures very low levels of residual disease. PCR at diagnosis and while FISH is greater than zero is largely meaningless. PCR <0.1% is a major milestone. You will see people on this forum discuss PCR's like 0.006 or 0.003 and they all mean little. Once PCR falls below 0.1%, the accuracy of the test is low and the amount of "CML" cells is minuscule in comparison to the amount of blood cells in circulation. It is however, a useful trend tracker to identify if response is lost. Once PCR falls below 0.01%, the measurement is indistinguishable from noise.

Many thanks Scuba. I really appreciate it for taking the time to explain the details. 

Hopefully I will have the latest results by Friday and will report on the PCR results. 

Have a great evening 

Mark