12 replies to this topic

[amurray]

I just got back a bcr abl1. I am very concerned and thought the experts here could give some input. My wbc and other blood counts are good,so i am confused. This is the results, please help me, I am a little scared:

BCR-ABL1, MAJOR (P210) QUANT RATIO     0.18544

BCR-ABL1, INTERNATIONAL SCALE (PERCENT)     13.1860

Unit: %

If someone can help me by letting me know how bad this looks it would be great!!

Amanda

[Trey]

It's been a couple years since we heard from you, and your PCR appeared to be quite low last we heard, but I do not know how the PCRs were reported.  That can make a difference by itself.

PCR reporting is not very patient-friendly.  Your first number above is reported as a ratio and the second number is a percentage.  So to compare the first to the second requires converting the ratio to a percentage, which is .18544 x 100 = 18.544%   This number is then converted to International Scale using a conversion factor that is unique to your lab.  So your PCR converted to IS scale is 13.186%  This number is a little less than a standardized 2 log reduction.  Since you were diagnosed in 2009, that is not a great number, but it is not awful either. 

You had been taking Sprycel, and I do not know if you are still taking it daily and the dosage.  Also, was the latest PCR from the same lab as the previous PCRs, and did they have International Scale conversions?

[amurray]

Hey Trey, it has been a while. I am so glad you answered! I am on sprycel 100 mg a day. My previous brc abl have been much lower . The last was actually a long time ago in 2011, it was the same lab the numbers were .00141 and on the international scale  .26%, I think. It seem like quite an increase. Thank you so much for taking time to help!

[Trey]

So it has been about 2 years since the last PCR, although proper procedure is a PCR every 6 months.  Not a good thing to do, but  you have said you have issues affording health care.  In those 2 years your PCR has increased roughly 1 1/2 logs, which is large enough that it requires investigation.  It would be advisable to have at least a FISH test done, and preferably also another BMB at the same time.  Or (somewhat less advisable) you could just repeat the PCR in a couple months to check on the validity of that last PCR.  Your small town doc does not appear to be taking very good care of you. 

[amurray]

I am actually having a bmb Tuesday,  I have have the FISH testing everything 3 to 6 months which I have opposed some because I feel a lot better with brc-abl1. The bcr did not increase that much when they advised the switch from Gleevec. This brc-abl1 was done on just blood.I am nervous what the BMB will show, does it typically show the roughly the same numbers as the blood? You are a blessing to all us Trey, truly!!

[Trey]

The PCR is equivalent enough done from either marrow or blood unless the marrow is changing quickly (due to disease rapid advance or decline). 

What have your FISH tests shown over the past year?

[amurray]

Trey just got done with bmb. The FISH results were 24%. During the bmb there was a lot of clotting and they had a hard time getting the marrow out, not a pleasant way to spend a beautiful tuesday, but now it is over. A week of waiting starts now, Uggg!

[Trey]

The FISH shows a clear loss of CCyR status, and is consistent with your recent PCR increases.  You may need to do something differently but will want to see what the BMB says.  

[amurray]

I got the FISH test back from the BMB, it showed 42%. I am really worried, what do you think?

[Trey]

That is not a good FISH result at this point.  I  highly recommend a Kinase Mutation Test to see if a kinase mutation caused the Sprycel to stop working (see links below).  That is not the only possible reason, but this test is needed to tell you if a specific drug is required since they do not all work the same against the various kinase mutations.  It is clear that you must change drugs, and also need to see what the BMB report says to see if it provides any clues (the BMB does NOT show kinase mutations, so a special test is required).  There are only a couple mutations which could do that, especially one called T315i that would require switching to Iclusig (Ponatinib) if you have it.  Otherwise Tasigna or Bosutinib are the other options.

http://www.aruplab.c...sts/0040138.jsp

http://www.cml-found...4-vep-branford2

[amurray]

The mutation test show positive for Q252H mutation. I am having trouble understanding what that means. Any info?

[Trey]

See this article, especially the red-yellow-green chart in Figure 1 which shows which drugs (Gleevec, Sprycel, and Tasigna only) are foiled by certain kinase mutations:

http://bloodjournal....110/7/2242.full

Q252H is the 4th kinase mutation listed in the chart, and is colored "yellow" for all 3 mainline drugs (Gleevec, Tasigna, and Sprycel).  This means these drugs only work to some degree against this type of mutation, so your results on any of them may be marginal. 

This color chart includes the TKI drug Bosulif, and shows that it overcomes Q252H:

http://jco.ascopubs..../27/3/469.short

This article says Ponatinib (Iclusig) can overcome Q252H mutation with 20mg dosage

http://www.ariad.com...Lf_SEPT2011.pdf

(See chart number 3)

The maker of Iclusig says that it "overcomes all clinical mutations tested".

http://www.ncbi.nlm....947601912462126

"ponatinib is active against many of the other imatinib-resistant mutations, including M244V, G250E, Q252H, Y253F/H, E255K/V, F317L, M351T, and F359V, among others"

So it would be a very good idea to switch to Iclusig (Ponatinib) or  Bosulif.  One of these should turn this around for you.  But you need to do this as soon as possible to avoid further loss of response.

[amurray]

Trey, thanks so much for all your help!!