16 replies to this topic

[snowbear]

My 12 month PCR results came in at 6.5% IS.  Diagnosis was 22.5%, hematologic response at 4 months, CCyr at 6 months.  But still not MMR.  

 

My last PCR was in July and it was 8.5%.  I just thought I would've made better progress in 6 months.  

[CML2012]

I understand. It took me 29 months to be PCRU. I was still at about 2% after 18 months. I started out at 53%. You are not alone.

[hannibellemo]

Snowbear,

 

The trend is down so that is always good. It isn't speedy but that's not necessarily bad or out of the ordinary. Could you attain benchmarks faster if you were taking Sprycel or Tasigna? Maybe, but you'll never know unless you switch. Switching could bring a whole different set of side effects that could be better or worse then what you are dealing with now,

 

You might want to give it another 3 months and see where you are at that time.

[Silvertabby]

I started on gleevec in October, 2013. Today the nurse called and said that I am PCRU. My response has been slow as well, but slow and steady is fine. I had a bit of a blip in June when my PCR supposedly went up to .58 from .159 three months before. But the results were inaccurate because the blood sample was suboptimal. They retested in September and it was .02. I now am very diligent to remind the lab to express the sample to Seattle so the lab receives the sample faster and tests it before the sample degrades too much. Hang in there. We are in this for the long haul.

[Trey]

The CCyR you have achieved is important.  Somewhat interesting that you were CCyR with a PCR of 8.5% last summer since normally one would expect CCyR below 1% PCR.  So it is possible that your personal PCRs "read higher" than others.  This is possible because some people have a different ratio of the control gene used (usually ABL1). 

 

If the next PCR shows a continued drop then this current one will look much better to you.

[alc999]

The CCyR you have achieved is important.  Somewhat interesting that you were CCyR with a PCR of 8.5% last summer since normally one would expect CCyR below 1% PCR.  So it is possible that your personal PCRs "read higher" than others.  This is possible because some people have a different ratio of the control gene used (usually ABL1). 

 

If the next PCR shows a continued drop then this current one will look much better to you.

 

Trey - What do you mean by "some people have a different ratio of the control gene used (ABL1)"? Could this be why my BCR-ABL was 195% at diagnoses? I'm curious about this because my BCR-ABL at 9 months (11/10/15) was 0.6%, which I was happy about. But my onc is not thrilled and wants me to consider switching my TKI if my 12 month isn't at 0.1 or below. Could I just have a different ABL ratio that makes me test high?

 

FYI - I reached CCyR at 6 months, at which time I had a BCR-ABL of 1.6%

[scuba]

Trey - What do you mean by "some people have a different ratio of the control gene used (ABL1)"? Could this be why my BCR-ABL was 195% at diagnoses? I'm curious about this because my BCR-ABL at 9 months (11/10/15) was 0.6%, which I was happy about. But my onc is not thrilled and wants me to consider switching my TKI if my 12 month isn't at 0.1 or below. Could I just have a different ABL ratio that makes me test high?

 

FYI - I reached CCyR at 6 months, at which time I had a BCR-ABL of 1.6%

 

Reaching CCyR at 6 months is terrific. Reaching CCyR is what is MOST important. CCyR is zero CML cells under the microscope and correlates approximately to 1.0% PCR. Your PCR continues to drop below that level. You should consider continuing your 3 month monitoring during which your PCR should continue to drop and very likely hit the next milestone target of 0.1% (major molecular remission). Keep in mind the accuracy range of the PCR test is one log or a factor of 10. In other words, you could be at 0.1% already.

 

Your Onc is being overly conservative and switching drugs is not necessary yet unless you have side effects that are interfering with your quality of life. You're doing fine. 

 

p.s. My baseline PCR was 155% at diagnosis. 

[Trey]

PCRs use a control gene to form a ratio of BCR-ABL1 (commonly called just BCR-ABL) to that selected control gene.  Most PCRs use ABL (actually ABL1) as the control gene.  ABL1 is in the BCR-ABL1, and is also found in normal cell DNA.  So the PCR compares BCR-ABL1 to the amount of overall ABL1 (both in BCR-ABL1 and ABL1 alone) to develop a percentage test report number.  One problem is that the amount of free ABL1 not associated with BCR-ABL1 can be different among various patients.  So two patients with the same relative "leukemic burden" would have different PCRs.  A second issue is that BCR-ABL1 and ABL1 degrade at significantly different rates over time.  So for a sample which is 1 day old vs 2 days old when tested can have very different results due to the difference in BCR-ABL1 vs ABL1 degradation rates.

 

The main issue to take away here is that PCR can be very inaccurate at higher levels, maybe above 10% PCR result.  As the leukemic burden decreases this becomes less of an issue.

 

These two issues are especially an issue with higher PCR numbers, and tends to even out with the lower PCR numbers. 

 

Here is what one article says:

 

"Although ABL is most widely used, our data suggest that the amount of ABL is different in CML and non-CML cells. Moreover, ABL levels are regulated by cellular stress. These findings have a direct impact on current clinical laboratory practice and patient care because the use of a proper control gene affects the reported levels of BCR-ABL transcripts used for patient management decisions."

http://www.ncbi.nlm....les/PMC1867593/

 

Here also is one of our members who had PCRs done with two different control genes on the same samples.  Note how the results are very different at higher PCR levels but tend to equalize at lower PCR levels:

http://community.lls...e-2#entry178990

[alc999]

Thank you both Scuba and Trey! I agree that my onc is being overly cautious, and he know that I'm uncomfortable with the idea of switching off of Gleevec unless there's a really good reason. This just helps bolster my decision to stay the course for now.

 

Trey, your explanation really helps me understand how I could have had a BCR-ABL greater than 100%, which has been something that has been bothering me since diagnosis. Now I can stop. My onc told me it meant I was an overachiever...which is funny, but didn't really help at all.

[snowbear]

It does confuse me why my FISH was 0% at six months, but my PCR's are still in the positive numbers. Onc wants to see where I'm at, at 18 months post-diagnosis before considering switching drugs.  I'm in no hurry to switch as it took me awhile to get used to the Gleevec and my side effects are much more manageable now.  I would hate to start all over with a new drug and maybe even worse side effects.

 

Doc was concerned though about my LDH.  At diagnosis, it was close to 900 and dropped to 150'ish within the first few months.  Now, it's up to 270.  The shortness of breath and chest pain have returned, but not as bad as before.  We don't know if it's the CML, an autoimmune issue (I have been flaring up over the past few weeks), or something else.  I've had enough heart and lung tests over the past few years that I'm not worried about that. So we are just watching it for now.

[snowbear]

Turns out that I HAVE made better progress than I thought. I'm not sure where the medical assistant got 6% from, but the results of my latest PCR test were posted on the hospital's forum this morning.  Come to think of it, my WBC was 6....anyhoo here are my results:

 

Specimen Type: Peripheral Blood (MO15-3977)

Assay performed: BCR/ABL1 Major transcript (p210) by quantitative real-time
PCR

Result:
BCR/ABL1 Major (p210) transcript: DETECTED (2.8480% IS or 0.4%
relative to K562 expression).

Comment:
The value reported represents a 0.301 log reduction from the immediate prior
value (PHB15-2966 from 7/21/15)
The value reported represents a 1.875 log reduction from our average
laboratory baseline of 30% for patients at diagnosis.

 

I'm still not <1.0% IS, but I'm getting there.  No doubt, I'll hit MMR by 18 months.  

[Terran]

Yay! Snowbear!

[snowbear]

Now, I'm really confused....and a bit worried.  More results were posted this morning.  My FISH has gone up from 0% last July to 3.4% in December.  This report recommends I undergo cytogenetic analysis...does that mean another BMB asap to look for mutations??  Should I call my doc or wait until my next appointment in March?

 

 

 

Fluorescence in situ hybridization (FISH) was positive for the BCR/ABL1 gene
rearrangement in 8 of the 237 interphase cells examined (3.4%). FISH
performed on the preceding specimen (a bone marrow aspirate, PHB15-2966 from
07/21/2015) was positive for the BCR/ABL1 gene rearrangement in 3.8% of the
interphase cells examined.

COMMENT:
The t(9;22)(q34;q11.2) translocation results in the transfer of the ABL1
oncogene from chromosome 9q34 to the BCR (breakpoint cluster region) gene on
chromosome 22q11.2. This leads to the formation of a fusion gene and
production of an abnormal protein with increased tyrosine kinase activity.
The latter plays a role in malignant transformation [Deininger MWN, Goldman
JM, Melo JW (2000) Blood 96:3343-3356].

Since only FISH studies were ordered, we cannot rule out the presence of other
chromosome abnormalities which often may be diagnostic for and/or precede the
hematologic and clinical manifestations of more malignant disease by several
months and thus, may serve as valuable prognostic indicators. Therefore, to
rule out the presence of additional chromosome alterations that are associated
with disease progression, you may wish to request classical cytogenetic
analysis.

[scuba]

Snowbear - do not wait. FISH going positive after being zero strongly indicates loss of response and is a more important indicator than PCR at this point. You need a bone marrow test so they can look at the cytogenetics for mutations. It is possible you are having a loss of response without any mutations and a change in drugs is in order. The time for that is now, not March.

 

From your report:

 

"Therefore, to rule out the presence of additional chromosome alterations that are associated

with disease progression, you may wish to request classical cytogenetic
analysis."

[Trey]

Something is odd about the way the FISH report is written.  The FISH was a bone marrow sample, so I think that is the old FISH report from a while ago since your recent PCR was peripheral blood.  FISH report also says "preceding specimen" like that was old news from a galaxy far, far away.  You didn't have marrow sucked out recently, did you?  If not, forget it since it is an old report.

[snowbear]

No, I've had 4 FISH tests so far.

 

12/14 - bone marrow biopsy - positive - 92.1%

 

6/15 -  peripheal blood - negative - 0%

 

7/15 - bone marrow biopsy - positive - 3.8%

 

12/15 - peripheal blood - positive - 3.4%

 

 

After the second marrow biopsy, doc did say it was normal for the BMB results to be higher than the PB results the month before. I looked back on my previous reports and that third paragraph was also on the 6/15 PB report so it seems that is just standard language when a BMB isn't done. I did call doc and left a message, but I haven't heard back. So I'm taking no news as good news and hope it's just a blip and will go back down by the 15 month test.

[Trey]

So the recent FISH was peripheral blood.  FISH can have a 1 - 2% error factor depending on type.  So FISH result is basically flat and PCR was lower than previous result.  Not speedy but acceptable.  No need to do anything in particular but I would shorten FISH and/or PCR cycle to 3 months.