Jump to content


Photo

Question for Trey


  • Please log in to reply
9 replies to this topic

#1 nia.435

nia.435

    New Member

  • Members
  • Pip
  • 7 posts

Posted 22 December 2013 - 09:38 AM

Hi Trey      

I was diagnosed in July 2012 with CML CP.

At 12 months on imatinub my results were as follows:

1 out of 20 metaphases of BMB was Philadelphia Chromosome POSITIVE.

PCR: 1.7 (IS)


My haematologist then switched me over to Dasatinub.  At 3 months on Dasatinub, my results were as follows:

1 out of 20 metaphases was still Philadelphia Chromosome POSITIVE. (No change).

PCR:  Results were not available yet.

My question to you Trey is: 

Is there any possible way that one can have a PCR <1 (CCyR) and at the same time have a BMB that is still Philadelphia Chromosome POSITIVE. (As in my case with only 1 metaphase still Philadelphia Chromosome Positive)?

My haematologist said that although I did not attain CCyR on Imatinub at 12 months, I still had a very good TKI response. I know it is still early days on Dasatinub and I am very close, but I am still worried about my response.

Thanks Trey

Vanessa



#2 Trey

Trey

    Advanced Member

  • PS Beta Group
  • PipPipPip
  • 1,705 posts
  • LocationSan Antonio, Texas

Posted 22 December 2013 - 10:03 AM

Vanessa,

Due to the small sampling of the white blood cells (WBCs) during a BMB cytogenetics analysis, there is the chance that a random leukemic cell could be found even for someone who has an even deeper response by PCR.  The cell selection is random but only looks at higher level WBCs (progenitor WBCs, not worker bee level WBCs) since these higher level cells show their chromosomes more clearly.  So even someone with a 3 log reduction (.1% PCR IS) could have a BMB analysis show a leukemic cell out of the 20 sampled. 

But at the one year point there is often a plateau in response because the TKI drug is starting to wipe out the leukemic cells which are higher level cells and harder to kill than the lower level cells which are killed off quickly when the TKI is first started.  These are the same higher level leukemic cells which can show up on a BMB, which is why they can show up more easily on the BMB exam while a PCR may still be dropping, since a PCR counts BCR-ABL derived from all levels of leukemic WBCs.

Overall you are doing well. You may see a plateau in PCR results for a few months, but don't think the TKIs are not doing their job unless there is a large spike in the PCR, which is unlikely for you. 



#3 nia.435

nia.435

    New Member

  • Members
  • Pip
  • 7 posts

Posted 23 December 2013 - 07:16 AM

Hi Trey,

Thank you so much for your advise. It really makes much more sense to me now and I feel so much better.  I am certain you know more about CML that some CML haematologists. We must all be greatful for having someone like you on this site.

Vanessa



#4 nia.435

nia.435

    New Member

  • Members
  • Pip
  • 7 posts

Posted 09 January 2014 - 05:11 AM

Hi Trey

Remember in our earlier discussion I asked you if there is any possible way that one can have a PCR<1 (CCyR) and at the same time have a BMB that is still Philadelphia Chromosome POSITIVE. (As in my case with only I metaphase still Philadelphia Chromosome Positive)?

Remember at 3 months on Dasatinub, I still had 1 metaphase out of 20 still Philadelphia Chromosome POSITIVE.

My PCR at 3 months on Dasatinub were not available at that time.

Well I received my PCR results for the 3 months on Dasatinib yesterday and It was as follows:

PCR: 0.264% (IS) (CCyR).

So you were completely right as my BMB still showed 1 metaphase still Philadelphia Chromosome Positive, but my PCR did an 85% drop from 1.7% (IS) at 12 months on Imatinub, to 0.264% (IS) at 3 months on Dasatinib.

So I have attained CCyR by PCR.  My haematologist still wants to do another BMB in 3 months time, but she said she is absolutely certain that the 1 metaphase that is still Philadelphia Chromosome Positive will have disappeared.

So Trey you were absolutely right.  I am really learning a lot about CML through you and this site.

Thanks.

Vanessa




#5 Trey

Trey

    Advanced Member

  • PS Beta Group
  • PipPipPip
  • 1,705 posts
  • LocationSan Antonio, Texas

Posted 09 January 2014 - 10:18 AM

Good to hear the news about the last PCR drop. 



#6 nia.435

nia.435

    New Member

  • Members
  • Pip
  • 7 posts

Posted 22 March 2014 - 04:19 AM

  

Hi Trey,

I just want to give you an update of my progress so far.  Just to recap.

-12 months on Imatinub: 19 out of 20 metaphases Philadelphia Chromosome NEGATIVE.

-PCR: 1.7% (IS)

My haematologist then switched me over to Dasatinub.

-3 months on Dasatinub: Still 19 out of 20 metaphases Philadelphia Chromosome NEGATIVE.

-PCR: 0.264%

I have just received my 6 months BMB results on Dasatinub and they are as follows:

-All 20 out of 20 metaphases Philadelphia Chromosome NEGATIVE. (CCyR by BMB).

-PCR: 0.199% (IS)

I am so happy I have finally got my CCyR by BMB.  Just to give you some idea why I am happy concerning my response and progress so far.

I was dx in July 2012 CML CP. My WBC=600k, Hb=6.7, Pts=167k, Blasts=1%. I don't know what my BCR-ABL was at diagnosis, but at 3 months it was 46.68%. At 6 months it dropped to 4.23%. I think my BCR-ABL at diagnosis must have been quite high.  My karyotype at diagnosis was as follows: 46, XX, t(4;5) (q21;q35), t(9;22;17) (q34;q11.2;p13) [20].

As you can see Trey I had a translocation involving chromosomes 4 and 5 and a three- way translocation involving chromosomes 9, 22 and 17.  I have done some research and I found out that additional chromosomal abnormalities can cause one to have a slower response on Imatinub.  My haematologist also said so.  Although I am at the 18 months mark from diagnosis, and have not achieved MMR ( I am very close) yet, my haematologist is so very happy with my progress and she said I will definately get there.  I have been reading some of your earlier posts on TKI response and I now realize that some of us take longer than others to reach MMR, but I am doing well.

Thank you so much Trey and everyone else for your advice and support, on this informative site. May God bless every one of you.

Vanessa



#7 Trey

Trey

    Advanced Member

  • PS Beta Group
  • PipPipPip
  • 1,705 posts
  • LocationSan Antonio, Texas

Posted 23 March 2014 - 09:52 AM

Interesting that you have two separate translocations, and that the main CML translocation is a 3-way.  You are quite the oddity.  T(9;22;17) is your main CML translocation with a bit of 17 thrown in.  That means that when your 9,22 swap occurred a piece of 17 that had also broken off attached to the broken piece of 22 along with the broken piece of 9.  The Philadelphia Chromosome is the new chromosome 22, so your Philadelphia Chromosome is the base part of 22 with broken off pieces of 9 and 17 attached (so 22, 9, 17 in order).  Most of us with CML have a broken piece of 9 attached to the broken 22 base.  As with all of us, the piece of 22 that goes and attaches to 9 is not relevant and apparently has no impact on the CML disease.

It is accurate that complex translocations often slow down the response to TKI drug therapy.  But the only issue is whether the patient responds, and that the response is sustained.  In some cases people with complex translocations can respond better than those with "normal" CML translocations.  So far you have done well, and since you are almost at the 2 year point since diagnosis, most people who get through 2 years doing well can expect continued success.

Regarding the separate t(4;5) translocation, it is very rare.  But oddly it is also a translocation which has responded to Gleevec in a number of cases.  Very good for you that it does.  This t(4;5) is a myeloproliferative disease similar to CML, but is called an "Atypical myeloproliferative disease".  I assume the t(4;5)  disappeared after the initial BMB since it was not mentioned in your later BMB reports from what you have said. 

Here is info on t(4;5) :

http://atlasgenetics...1q33ID1510.html

Also remember that your translocations only apply to your blood cells.  You may read about t(4;5) translocations which affect the skin, but those are not blood cells, so ignore such information. 



#8 nia.435

nia.435

    New Member

  • Members
  • Pip
  • 7 posts

Posted 24 March 2014 - 07:59 AM

Hi Trey,

Thanks for all the information and encouragement.  Maby I never explained myself properly involving my karyotype with my various BMB's.

Karyotype at diagnosis: 46, XX, t(4;5) (q21;q35), t(9;22;17) (q34;q11.2;p13) [20].

3 months on Imatinub:46, XX, t(4;5) (q21;q35), t(9;22;17) (q34;q11.2;p13) [13]

6 months on Imatinub:46, XX, t(4;5) (q21;q35), t(9;22;17) (q34;q11.2;p13) [3]

12 months on Imatinub:46, XX, t(4;5) (q21;q35), t(9;22;17) (q34;q11.2;p13) [1]

3 months on Dasatinub:46, XX, t(4;5) (q21;q35), t(9;22;17) (q34;q11.2;p13) [1]

6 months on Dasatinub:46, XX

So as you can see Trey, the t(4;5) remained with me from diagnosis through 3,6, 12 months on Imatinub and then at 3 months on Dasatinub.  At 6 months on Dasatinub It was a normal female karyotype.  I see from the link to the article you gave me, that the t(4,5) responds well to Imatinub.  I have had a very good TKI response, albeit a little slower.  I was only diagnosed with CML, not a-MPD or anything else.

Thanks Trey,

Vanessa 



#9 Trey

Trey

    Advanced Member

  • PS Beta Group
  • PipPipPip
  • 1,705 posts
  • LocationSan Antonio, Texas

Posted 24 March 2014 - 09:53 AM

Vanessa,

As you can see by your karyotype numbers at the end of each line in brackets, such as [20], [13], [3], etc, those show two things.  They are the numbers of leukemic cells found when 20 cells were examined from the BMB sample, but they also show that the t(4;5) chromosome abnormalities were only in the leukemic cells since the t(4;5) do not have their own brackets with separate numbers.  That is important.  So the leukemic cells are the only ones with t(4;5), and as the leukemic cells are killed off, the t(4;5) issue also goes away at the same time.  That is why you do not have a secondary diagnosis other than CML, which is good.

So you have had a steady response to TKI drugs over 21 months.  It is not clear why you were switched from Gleevec at 12 months since it seemed to be doing the job well enough for you, but there is no problem with switching drugs, either.  It is good news that your complex translocation responds to either Gleevec or Sprycel.  Also, you are nearly past the 2 year point where patients have less chance of relapse.  These are a good indicators that you will have a good long term response despite the complex translocation.

Thank you for sharing your story and information.  Others coming along in the future will learn from your success that complex translocations are not necessarily a problem for TKI drugs, even though the response may be somewhat slower.



#10 nia.435

nia.435

    New Member

  • Members
  • Pip
  • 7 posts

Posted 25 March 2014 - 06:09 AM

Hi Trey,

Thanks for clarifying things concerning the t(4;5) chromosome. I now understand. My haematologist switched me from Imatinub to Dasatinub at 12 months, as she was following The ELN Recommendations For The Management Of CML (2010). At 12 months one must have CCyR by BMB for Optimal Response. 

As you know I just missed CCyR by BMB at 12 months. She switched me as I dropped to Suboptimal response at 12 months and she said she was also concerned about my response because of my Complex Karyotype. My doctor is pro-active and she is very cautious.  She also said I did extremely well on Imatinub and my graph of my BCR-ABL shows a good, steady decline from diagnosis to present. Exactly like you said.

Trey, I have learned such a lot from you and this site. I have read many of the stories posted here, and they have really helped me greatly.  That is why I decided to tell you my story, so that you can relay my story to anyone in the future with similar Complex Karyotypes and it will also motivate them, and like you said know that there is success with TKI's regarding Complex Karyotypes, even if there is a slower response.

Thanks

Vanessa






1 user(s) are reading this topic

0 members, 1 guests, 0 anonymous users