9 replies to this topic

[Rice]

I'm meeting with Dr. Kantarjian for the first time next week and I could use some help in knowing what to ask and the most direct way to go about it to make the most out of my appointment.

I'm 30 years old and was diagnosed back in May. I've been on Sprycel 100mg since and as of two weeks ago my blood counts are near normal. My biggest concern is that I have no idea how much of the BCR-ABL remains. My PCRs have all come back negative and I'm told this is due to having a different break point than normal. I was also told that only a few labs can or will test this specific case and that's why I'm heading to MD Anderson to potentially find out exactly what's going on.

If I haven't explained this well enough I apologize. I just want to better articulate what I need without wasting time. Bottom line, I want to know how I'm responding to the treatment and I want a number to attribute my level of response too. Thanks for any help!

[Dom]

Hello Rice.  You did a good job explaining your situation to us, so I think you're ready to meet with your new Onc.  There are very very few instances on this board of Oncs who are not responsive, but for the most part they do a good job answering questions.  I have to say, though, that I'm surprised no one is telling you about your BCR-ABL.  That's important information.  

 

I go to Anderson too.  I have no complaints.    

[Trey]

Standard PCR only tests for three BCR-ABL breakpoints, namely e13a2 (b2a2), e14a2 (b3a2), and e1a2.  That is because 99% are these three breakpoints.  Sometimes e1a2 is not even tested unless requested.  There are other rare BCR-ABL breakpoints with names like e19a2, e2a2, e1a3, e6a2, e13a3 (b2a3), and e14a3 (b3a3).  You first need to ask which of these you have.

http://www.bloodjour...so-checked=true

 

FISH and BMB cytogenetics can detect all breakpoints, so FISH should be the primary method of testing disease levels for you until it becomes negative.  If you do not have e13a2, e14a2, or e1a2 then your PCR will always be negative regardless of response or lack thereof.

 

You could message me and attach a copy of your BMB report and I could explain what it says.

[Rice]

Thank you for helping to explain Trey. The information I have relating to my BMB report seems to be very lacking so I'm trying to find a more detailed report (hopefully from the lab that performed the test). Upon further reading, I do have positive FISH results, but it is considered abnormal. I'm not sure what sense to make of that (if it's related to the abnormal breakpoint like PCR results or something else). 

 

My oncologist thinks that I could have a P230 breakpoint or a variant of P210 (e13a3 or e14a3). I'm starting to get overwhelmed looking through everything since I'm not sure what exactly I'm looking for and I have the feeling that I'm missing reports even though I requested "everything." I have a Flow Cytometry Report (includes Lymphoma Leukemia Phenotyping Report), a Surgical Pathology Report (BMB information) and a chromosome analysis w/ the following results:

 

 

-------------------------------------------------------------------------------------------------------------------------------------------------------------------------

Chromosome results: 46,XY,t(9;22)(q34;q11.2)[12]/46,sl,inv(7)(p12p22)[10]

Diagnostic Impression:

Two cell lines were detected in multiple cultures from this
patient. One cell line showed the Philadelphia (Ph)
translocation between chromosomes 9 and 22 in 12/22 (55%) cells. The remaining 10/22 (45%) cells showed an inversion in the short arm of chromosome 7, in addition to the t(9;22).

This result is consistent with a diagnosis of a Ph-positive leukemia.

NOTE: FISH was performed on this sample and reported. FISH results were ABNORMAL, and showed an atypical BCR/ABL1 rearrangement signal pattern which may include additional chromosomally invisible structural change. 

-------------------------------------------------------------------------------------------------------------------

 

Please help make sense of this for me.

[Rice]

From my FISH results:

 

ABNORMAL FISH RESULT

t(9;22)(q34;q11.2) (ABL1;BCR): translocation present (*atypical signal pattern*)

DIAGNOSTIC IMPRESSION:
Fluorescence in situ hybridization (FISH) analysis was performed with the BCR/ABL1/ASS1 Tricolor Dual Fusion probe (Abbott Molecular).

This analysis showed evidence of a fusion of ABL1 with BCR in 189/200 (94.5 percent) cells scored.

This finding is consistent with a diagnosis of a Philadelphia translocation-positive leukemia.

*The signal pattern observed was consistent with a der(22) and BCR-ABL1 fusion but showed two normal patterns for the ABL1/ASS1 loci; this pattern may indicate a loss of BCR sequence from the der(9), two normal copies of 9, or a more complex rearrangement involving these loci.

ISCN:
nuc ish(ASS1x2,ABL1x3,BCRx2)(ABL1 con BCRx1)[189/200] 

 

 

*From what you've said Trey regarding disease levels is the 94.5% what I should be tracking? Should I be able to track log reductions or is it different in my case?

[Trey]

An "abnormal" FISH simply means it detected the leukemia.  The report says the FISH detected 189 leukemic cells out of 200 cells sampled, so 94.5%.  At diagnosis this level is fairly standard.  So this is what you should track for progress or lack thereof, and you need to have FISH tests done regularly.  Your BMB showed 12 out of 22 cells examined by microscope were leukemic.  The percentage variation from FISH is not an issue -- both show CML.  If your PCR was negative, that likely shows it is not P210 CML.  Maybe the PCR tested for P190 CML and maybe it didn't so you need to ask.

 

You also have a second chromosome abnormality on chromosome 7 called "Inversion 7" which is very rare.  It is only in the non-leukemic cells, which may or may not be significant.  Some of these issues are actually caused by the TKI drug treatment, and if this is the cause they usually disappear on their own without negative consequences.

 

There may also be micro-deletions of genetic material inside the Philadelphia Chromosome (the leukemic translocation).  It could be on chromosome 9 or 22 or both.  The report discusses this but draws no conclusion.

 

You sent your BMB report to me.  There is little information on the BMB report because the attempt to extract marrow fluid failed due to a dry marrow cavity (dry tap).  So they only evaluated the core sample and then sent out a peripheral blood sample to have a second analysis performed.  Do you have that second BMB analysis report?

 

Hopefully you had additional FISH tests done since the one at diagnosis 4 months ago -- what did it say?  If not, you need one right away.  If it can be done before seeing Dr Kantarjian that would be better.

 

This is a case where a CML specialist is very important.  Dr. Kantarjian at MDA should be able to help you understand these issues better.

 

I would ask Dr. Kantarjian these questions:

1) What type of Philadelphia Chromosome do I have -- something other than P210?  What is the significance?

2) Do I have micro-deletions on the Philadelphia Chromosome?  If so, on chromosome 9 or 22, or both?  What significance are they?

3) Describe the Inversion 7 issue and its significance related to CML.  Was this likely caused by the TKI therapy?

4) Should another BMB be done since the first was a dry tap?  What did the peripheral blood BMB show, and was it adequate for my diagnosis?

5) Am I in Chronic Phase CML?  Is there a risk I could have (or develop) something other than CML because of the abnormalities?

5) Am I responding well enough to Sprycel?  Should my drug therapy be altered in any way?

6) What testing schedule is needed, and what tests should be done? 

 

You should get copies of every report your current Onc has.  You could send them to me and I can help prepare you further for your appointment.

Edited by Trey, 10 September 2015 - 06:19 PM.

[Trey]

You sent me a more recent FISH report which was undetected.  That would indicate the drug has worked well for you since the FISH can no longer detect the leukemia.  That is very good news and indicates you have already achieved Complete Cytogenetic Response (CCyR).  That is a major milestone.  Given your complicated chromosomes, that is fantastic.  The issue now is maintaining that response for at least 2 years, and then you enter a "safe zone" of sorts.

 

FISH can only detect to a certain level, and PCR is needed beyond that to track drug response below CCyR levels.  If you have a Philadelphia Chromosome translocation other than P210 or P190 which cannot be detected by PCR, that additional level of response monitoring would not be possible for you.  So you would just need to keep having FISH to ensure you do not lose CCyR, and also probably have "regular" BMBs to assure the Inversion 7 goes away.  Once the BMBs no longer detect either Philadelphia Chromosome or Inversion 7 the BMBs can stop.

 

So a revised list of questions for Dr. Kantarjian:

1) What type of Philadelphia Chromosome do I have -- something other than P210?  What is the significance?

2) Do I have micro-deletions on the Philadelphia Chromosome?  If so, on chromosome 9 or 22, or both?  What significance are they?

3) Describe the Inversion 7 issue and its significance related to CML.  Was this likely caused by the TKI therapy?

4) Should another BMB be done since the first was a dry tap?  What did the peripheral blood BMB show, and was it adequate for my diagnosis?

5) Am I in Chronic Phase CML?  Is there a risk I could have (or develop) something other than CML because of the abnormalities?

6) My second FISH was undetected.  So I assume I am responding well enough to Sprycel?  Should my drug therapy be altered in any way?

7) What testing schedule is needed, and what tests should be done?  Is FISH and BMB the correct way to track disappearance of both the Philadelphia Chromosome and Inversion 7, and monitor for continued drug response?  Is there a special PCR which can monitor my progress beyond CCyR?

[Rice]

So I noticed shortly after sending the second FISH to you that the blood was collected on 8/26, received at the lab on 8/28, and completed on 9/7. Could this large date gap between collection and completion degrade the specimen to result in an undetected FISH?

Thanks Trey. You're beyond helpful.

[Trey]

Completed date is just the final report review date, not the date the lab did the FISH.  So it appears your FISH was done correctly.

 

FISH is not as dependant on quick processing as PCR.  PCR requires live cells but FISH does not.  Although FISH requires a sample which is not degraded at the cellular level, it is preserved in a different preservative medium (sodium heparin) which keeps it intact longer than the PCR medium (EDTA), although not alive.

[AngSuper]

Hello Rice,
I cannot give you advice on your condition but I wanted to let you know you are in fantastic hands. I am 34 yrs old diagnosed with AML and I went to MD Anderson from Pa for a second opinion. My Dr is Dr Kantarjian and he and his team are the best of the best. I think the world of them and I believe you will too. Prayers to you.