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BCR-ABL uptick

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I was diagnosed last year with CML, started with Dasatinib 100mg from Oct 2019, but the recent 1yr BCR-ABL result is concerning me. Every 3months result was trending down except the 12month one. I’m meeting the doctor next week, not sure what he will say..Is there anything I should ask him?

My history,

Sept 25th - Diagnosed with CML

Oct 1st 2019- started Dasatininb 100mg

Jan 2020- 6.78 IS

Apr 2020- 0.86 IS

Jul 2020- 0.74 IS

OCT 2020 - 0.75( b2a2) 0.19(b3a2) both are in IS- total .94(I’m intrepreting this as sum of individual)

This is the first time the results are reported seperately for these transcriptions(I thought I had only b3a2 per prior PCR test) and looks like they have used a different lab this time as per the results online. 
appreciate any insights on why it may be higher this time. Starting to worry and Waiting to see what Dr has to say.

Hey there,

First of all any uptick causes great anxiety and I get it. But looking at those upticks they’re all around the same number. We on the forum panic - the doctors don’t as they’re really the same results. PCR testing is very sensitive you could have the test done 3 times in the same day and you’d get differing results. That’s positive 1.

Second a change in lab is never great as they use different machines and some aren't calibrated the same. That’s positive 2.

I like you didn’t reach MMR at 12 months, or 24 months but I bounce around lately at 0.1% which is almost MMR but not quite. In fact have my 2.5 year blood test today. Not holding my breath but would be nice to be MMR now. But I’ll be happy if I am at least stable and below 1% with no considerable increase.

So the take home is although hard don’t panic these really are all the same results looking at your numbers with slight fluctuations for many different reasons.

All the best

Alex

 

Thanks Alex, I was 39yrs when diagonised. Achieved hematological response in 2 weeks and CCYr in 6 months. Asking my doctor to reschedule to today or tomorrow since it is a virtual visit.

No problem. Same as me on those milestones, things have slowed since reaching CCYR and ironically been stuck on the MMR line. 37 at diagnosis. Tested today myself, doesn’t seem to get easier the process but here we are...

All the best

You appear to be in the same boat as me. I am bobbing around MMR, which I am assured is satisfactory, but making no further progress.

Do you know your transcript type? I am e13a2 (b2a2)? This transcript type appears to yield inferior results. 

First time I’m seeing both transcripts(e2a2 and e3a2) in my bcr-abl results as my hospital used different lab this time.

Not sure if b2a2 is new or detected now due to a different(more advanced) machine.

At my 1month mark, I went to Augusta health to consult Dr cortes because of myelosuppression, they did my blood work and confirmed only b3a2.

 My primary hematologist is repeating a bcr-abl test and ordered a mutational analysis.

hopefully pcr value is not rising..we have discussed therapy switch to either Nilotinib or Busotjnib as well. Fingers crossed as the next step depends on the pcr  results.

 

 

Yeah so far bobbing around MMR was on last 2 tests. Just had my 2.5 year test as I test 6 monthly get the result in November (still no mutation report over 6 months now). So we will see I am not holding my breath on a reduction but anything other than a rise I’ll be happy with. I am regular p210 only...

I just got the repeat of BCR-ABL results today which is 1.2, increase from 0.95. Still waiting on mutation analysis results.

I'm really worried now, I've a followup appointment with my doctor this week. What can be the next steps here? Options my doctor discussed last time with me were

1. Switch to either Nilotinib or Bosutinib

2.  Increase Dasatinib to 140mg

3.  Continue on Dasatinib 100mg and do more frequent monitoring

#3 was the least preferred option per my doctor last week, but not sure if that is an option  anymore since the latest results are up from last week.  

of course, everything changes if there is a mutation where 2nd gen TKI doesn't work. In that case only 3rd gen TKI(Ponatinib) is the only option.

I would greatly appreciate your response if you have encountered something similar with Dasatanib or any other TKI or any suggestion/guidance is welcome.  This is really making me nervous.

 

 

 

 

Hi Brett,

I understand your concern. It's never nice when the numbers don't continue to go down.

I would have thought trying another TKI would be worth a try. We do see patients who do better on one TKI, even when there's no defined mutation, so there's every chance you could be like that.

Dasatinib at 140mg feels like a longer shot - side effects (particularly fluid on the lungs) increases with that dose, and 100mg is already a good whack of a dose.

Just to rule things out, are you taking any other medication as well as dasatinib? Or any supplements?

David.

Thanks David, No I’m not taking any other medication or supplements except Sprycel.

My understanding is that the transcripts b2a2 or b3a2 code for a p210 protein.

This short video may be helpful.

https://cmlsupport.org.uk/videos/second-and-third-generation-tkis-%E2%80...

50% of patients are super responders. 

10% suffer from primary resistance and 10% suffer from secondary resistance.

30% plateau.

 

Good informational video, thanks for sharing

That's right. The e1a2 RNA encodes p190 fusion protein. b2a2 or b3a2 encode the p210 fusion protein, which is the most common for us lot. c3a2 encodes the even lesser spotted p230 protein which seems to generate something that is similar to, but not quite CML

David.

Thank you, David.

I cannot find the appropriate authority now but I have seen a video in which Prof Jane Apperley suggest that those with the b2a2 transcript type experience greater difficulty achieving deep responses to TKIs and may not be the best candidates in the longer term for treatment free remission.

 

You might be thinking of this one: https://vimeo.com/220445547

I don't have the time to watch it now to check, but the title of that session was "Are we ready for recommendations to stop outside of trials?"

David.