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BCR-ABL Transcript Type Predicts Response and Survival Among Patients with CML


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#1 gerry

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Posted 03 March 2016 - 08:53 PM

The presence of one or both of the most common BCR-ABL transcripts in patients with chronic-phase chronic myeloid leukemia (CML), e13a2 and e14a2, is predictive of response to tyrosine kinase inhibitors (TKIs) and longer survival, according to results from a recent report in Blood.

http://ashclinicalne...ients-with-cml/

#2 Trey

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Posted 03 March 2016 - 10:43 PM

Weird.  Those patients with both e13a2 (b2a2) and e14a2 (b3a2) responded better to TKI treatment than those who had one or the other.  Probably a statistical sampling thingy.

 

But I have been wondering if transcript type is a determining factor in cessation success.  Possibly e13a2 (b2a2) could be harder to keep in check?



#3 gerry

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Posted 03 March 2016 - 11:47 PM

I wonder if there may be different reasons why the CML appeared for some of us. And if it was for a particular reason, why some of us have been able to stay off a TKI.

#4 Frogiegirl

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Posted 04 March 2016 - 02:33 PM

Trey.....this question may be dumb but I'll ask anyhoooo. ....how do you know which transcript you are or have? I looked all over my bmb/fish results at diagnosus and all they say are the 9 and 22 chromosome rearrangement?

Diagnosed Oct 2013 Started 600mg of Tasigna  on Nov 4th. Lowered dose a few months later to 300mg due to side affects stayed here declining PCR until March 2015 small jump from 0.0072 to 0.0083 scarred my doc into full dose of Tasigna again 600mg(been miserable since) but reached PCRU 06/15/2015(next test) and have been there ever since. Hoping to have another little one. I have the support of my doc to go off anytime, just scared to jump. might go two years PCRU but he said it wont make much of a difference. I just figured I could possibly go into a trial while preggers if I got the two years behind me.

Nov 8th 2017 went off Tasigna

Dec 1st PCRU off TKI

Jan 5th PCR Detected .0625

Feb 1st PCR Detected .7815

Added 8-6 grams Curcumin daily in Feb

March 3rd PCR Detected 3.2646 YIKES!

 stopped trying for baby after February reading. will start new TKI march 16th 2017 (Sprycel)

FYI I'm not done trying for my last little one.


#5 Trey

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Posted 05 March 2016 - 09:51 AM

Both PCR and FISH can determine the transcript type.  But it may not be reported unless asked for.  It is often reported at diagnosis, but maybe not after that.



#6 Gail's

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Posted 05 March 2016 - 03:11 PM

So I'm entering what I think are the pertinent results from both my initial BMB and the repeat at 1 year post diagnosis. Based on my latest results I've switched from 400 mg gleevec to 100 mg sprycel. GI effects are better, muscle aches, fatigue, insomnia worse and I'm discouraged. I had a really hard time for about 3 mos with onset of gleevec, got better over time although sharts were a pain. I would like to use higher dose of gleevec rather than sprycel due to upcoming retirement (649 days). Doc is worried I'll still have GI difficulties and wants me to stick with sprycel.

Feb 2015
Hyper cellular marrow 95% with trilineage hematopoiesis.
Myeloid hyperplasia with left-shifted myelopoeisis
Atypical megakaryocyte hyperplasia
Diffuse to moderate reticulum fibrosis
Less than 5% blasts
Peripheral blood with neutrophil is, monocytes is, eosinophilia and basophila (6%)
No increase in blasts 1%
Bar/abl positive by molecular analysis.

My fish about a week later was 92%

Feb 2016
Peripheral blood with normochromic, normocytic anemia
Normocellular bone marrow with trilineage hematopoiesis
Approximately 3% myeloid blasts
T(9;22) detected by fish in 3.5% of cells; normal karyotype
Comment:
Bone marrow is normocellular with trilineage hematopoiesis. There is no significant increase in dysplastic features. Myeloid blasts are approximately 3% of the bone marrow by CD34 staining. There is no evidence of a lymphoproliferative disorder.
Amendment:
The cytogenic studies show a normal karyotype. The fish studies show the bcr/abl present in 3.5% of cells, consistent with treated CML.
Diagnosed 1/15/15
FISH 92%
BMB 9:22 translocation
1/19/15 began 400 mg gleevec
1/22/15 bcr 37.2 IS
2/6/15 bcr 12.5 IS
3/26/15 bcr 10.3 IS
6/29/15 bcr 7.5 IS
9/24/15 bcr 0.8 IS
1/4/16 bcr 0.3 IS
Started 100 mg dasatinib, mutation analysis negative
4/20/16 bcr 0.03 IS
8/8/16 bcr 0.007 IS
12/6/16 bcr 0.002 IS
Lowered dasatinib to 70 mg
4/10/17 bcr 0.001 IS
Lowered dasatinib to 50 mg
7/5/17 bcr 0.004 IS
8/10/17 bcr 0.001. Stopped TKI in prep for September surgery.
9/10/17 bcr 0.006
10/10/17 bcr 0.088

#7 Trey

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Posted 05 March 2016 - 03:52 PM

BMB cytogenetics is zero but FISH is 3.5%.  This is CCyR since the BMB is zero.  FISH is slightly positive, and although it could be false positives it is probably accurate. 



#8 rcase13

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Posted 05 March 2016 - 04:58 PM

b3a2 is what was in my paperwork. I had a good fast response to Tasigna but after 15 months have never reached PCRU. If enough of us post results maybe we can learn something from it. But most likely the pool of people posting is really too small to tell.

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

 

Cancer Sucks!


#9 gerry

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Posted 05 March 2016 - 07:44 PM

Weird.  Those patients with both e13a2 (b2a2) and e14a2 (b3a2) responded better to TKI treatment than those who had one or the other.  Probably a statistical sampling thingy.

 

But I have been wondering if transcript type is a determining factor in cessation success.  Possibly e13a2 (b2a2) could be harder to keep in check?

I see my doc on Tuesday, so will ask him, give the doc and I something extra to talk about. I couldn't find this info on any of my initial reports from the two BMBs. Will see how I go with him. 



#10 gerry

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Posted 05 March 2016 - 09:21 PM

I can see a bit more info on my second BMB undertaken 4 months after starting gleevec, though still not the info on the transcripts

At 4 months treatment I had 64% T cells: B Cells 11% and NK cells 20%.



#11 Gail's

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Posted 06 March 2016 - 12:02 PM

Trey, is it significant that blasts are still there? My doc also did resistance studies that were negative.
Diagnosed 1/15/15
FISH 92%
BMB 9:22 translocation
1/19/15 began 400 mg gleevec
1/22/15 bcr 37.2 IS
2/6/15 bcr 12.5 IS
3/26/15 bcr 10.3 IS
6/29/15 bcr 7.5 IS
9/24/15 bcr 0.8 IS
1/4/16 bcr 0.3 IS
Started 100 mg dasatinib, mutation analysis negative
4/20/16 bcr 0.03 IS
8/8/16 bcr 0.007 IS
12/6/16 bcr 0.002 IS
Lowered dasatinib to 70 mg
4/10/17 bcr 0.001 IS
Lowered dasatinib to 50 mg
7/5/17 bcr 0.004 IS
8/10/17 bcr 0.001. Stopped TKI in prep for September surgery.
9/10/17 bcr 0.006
10/10/17 bcr 0.088

#12 Trey

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Posted 06 March 2016 - 09:13 PM

Trey, is it significant that blasts are still there?

1% is fine for marrow.  Under 3% would be OK.



#13 Gail's

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Posted 07 March 2016 - 10:10 PM

2nd bmb report said 3% myeloid blasts. Is that ok?
Diagnosed 1/15/15
FISH 92%
BMB 9:22 translocation
1/19/15 began 400 mg gleevec
1/22/15 bcr 37.2 IS
2/6/15 bcr 12.5 IS
3/26/15 bcr 10.3 IS
6/29/15 bcr 7.5 IS
9/24/15 bcr 0.8 IS
1/4/16 bcr 0.3 IS
Started 100 mg dasatinib, mutation analysis negative
4/20/16 bcr 0.03 IS
8/8/16 bcr 0.007 IS
12/6/16 bcr 0.002 IS
Lowered dasatinib to 70 mg
4/10/17 bcr 0.001 IS
Lowered dasatinib to 50 mg
7/5/17 bcr 0.004 IS
8/10/17 bcr 0.001. Stopped TKI in prep for September surgery.
9/10/17 bcr 0.006
10/10/17 bcr 0.088




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