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BCR-ABL Transcript Type Predicts TKI Response in CML


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#1 Buzzm1

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Posted 08 January 2016 - 12:07 AM

BCR-ABL Transcript Type Predicts TKI Response in CML http://www.cancerthe...article/463515/

 

Patients with chronic myeloid leukemia (CML) in chronic phase who have e13a2 BCR-ABL transcripts have inferior outcomes when treated with imatinib 400 mg, while those with e14a2 have favorable outcomes regardless of tyrosine kinase inhibitor (TKI) therapy, a study published in the journal Blood.1


For the benefit of yourself and others please add your CML history into your Signature

 

02/2010 Gleevec 400mg

2011 Two weakly positives, PCRU, weakly positive

2012 PCRU, PCRU, PCRU, PCRU

2013 PCRU, PCRU, PCRU, weakly positive

2014 PCRU, PCRU, PCRU, PCRU (12/07 began dose reduction w/each continuing PCRU)

2015 300, 250, 200, 150

2016 100, 50/100, 100, 10/17 TFR

2017 01/17 TFR, 04/18 TFR, 07/18 TFR 0.0012, 08/29 TFR 0.001, 10/17 TFR 0.000

2018 01/16 TFR 0.0004 ... next quarterly PCR 04/17

 

At the earliest opportunity, and whenever possible, lower your TKI dosage; TKIs are toxic drugs and the less we take longterm the better off we are going to be ... this is especially true for older adults.  

 

In hindsight I should have started my dosage reduction two years earlier; it might have helped minimize some of the longterm cumulative toxic effects of TKIs that I am beset with.  

 

longterm side-effects Peripheral Artery Disease - legs (it's a bitch); continuing shoulder problems, right elbow inflammation.   GFR and creatinine vastly improved after stopping Gleevec.

 

Cumulative Gleevec dosage estimated at 830 grams

 

Taking Gleevec 400mg an hour after my largest meal of the day helped eliminate the nausea that Gleevec is notorious for.  

 

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#2 rcase13

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Posted 08 January 2016 - 08:07 AM

I will have to try and get my bone marrow results to see what I have. Thanks

10/01/2014 100% Diagnosis (WBC 278k, Blasts 6%, Spleen extended 20cm)

01/02/2015 0.06% Tasigna 600mg
04/08/2015 0.01% Tasigna 600mg
07/01/2015 0.01% Tasigna 600mg
10/05/2015 0.02% Tasigna 600mg
01/04/2016 0.01% Tasigna 600mg
04/04/2016 PCRU Tasigna 600mg
07/18/2016 PCRU Tasigna 600mg
10/12/2016 PCRU Tasigna 600mg
01/09/2017 PCRU Tasigna 600mg
04/12/2017 PCRU Tasigna 600mg
10/16/2017 PCRU Tasigna 600mg
01/15/2018 PCRU Tasigna 600mg

 

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#3 Trey

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Posted 08 January 2016 - 09:24 AM

There may be something to it, but there may also just be some statistical issues involved.  There was another clinical trial involving over 1000 participants which concluded "clinical outcome under imatinib treatment was comparable and no risk prediction can be made according to e13a2 versus e14a2 BCR-ABL1 transcript type at diagnosis."

http://www.ncbi.nlm....pubmed/24837466

 

The report cited by Buzz shows that e13a2 results in higher WBCs while e14a2 results in higher platelet counts.  That might cause some statistical issues when using log reductions as a measurement.  But again, there may be something to the issue, but probably not a big deal.  Oddly, the report also concludes that if someone has both e13a2 and e14a2 they do better than if they only have the e13a2 (b2a2) alone. 

http://www.cancerthe...article/463515/



#4 missjoy

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Posted 08 January 2016 - 12:10 PM

The following is what I found. Does anyone know how to compare p190, p210and p230 to e13a2 and e14a2?

http://www.ncbi.nlm....les/PMC2193055/

#5 Trey

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Posted 08 January 2016 - 12:41 PM

P210 is e13a2 (b2a2) and e14a2 (b3a2)

P190 is e1a2

P230 is several types with higher numbers such as e19a2, etc.

 

 

98% of CML patients have the P210 breakpoint.


Edited by Trey, 08 January 2016 - 06:48 PM.


#6 missjoy

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Posted 08 January 2016 - 01:24 PM

Thank you very much Trey!! I am so impressed by your knowledge and kindness to others. Wish you a good 2016!

#7 snowbear

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Posted 08 January 2016 - 04:31 PM

Interesting, I have P210 and am a slow-ish responder.  My WBC was moderately high prior to diagnosis (15-55) and platelets high (400-600).  



#8 Lucas

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Posted 08 January 2016 - 04:35 PM

don't believe in this issue. i rememer i read a paper when i was first dx saying that people with b3a2 are more prone to have a worse outcome and than i found other paper that said that people with b2a2 have a worse outcome on gleevec. my transcript is b3a2 and i failed gleevec within 7 months.






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