6 replies to this topic

[LivingWellWithCML]

Hi everyone,

I know we've dabbled on this topic in some other threads, but I wanted to resurface and get some opinions from you all on our (and our CML specialists') confidence in the use of peripheral blood (PB) for CML treatment monitoring.  Especially as I approach an important treatment milestone.

To set context, I received a lovely BMB/A to confirm dx at the end of March 2011, started Gleevec 400mg in mid-April, had 3-month FISH/PCR done on PB only in mid-July (FISH = 5%, PCR = 0.72 log decrease from an 'average' untreated chronic phase baseline value), and am scheduled to have 6-month FISH/PCR testing in mid-Oct ... also exclusively from PB.  My CML specialist is planning to monitor my response exclusively through PB moving forward ... unless there is a specific need to do otherwise.  He specifically referenced a study that he was a co-author on ... this paper concludes that PB is an acceptance method for treatment monitoring and correlates very well with marrow:

• Peripheral Blood Monitoring of Chronic Myeloid Leukemia During Treatment With Imatinib, Second-Line Agents, and Beyond
  

I managed to get ahold of a copy of the paper -- it's nice to have a neighbor who's a molecular genetics professor <grin>.  Anyway, I gave it a read with my statistics hat on ... looked at the various graphs and such, and have drawn some of my own conclusions:

• In comparing PB FISH to BM Cytogenetics (CTG) and to BM FISH, the test results are extremely close if the patient is ~ >= 90% Ph+ or ~ <= 30% Ph+.  There are some freaky outliers though (e.g., PB FISH ~ 10%, but BM CTG data points at 60%, 80%, and even a couple at 100%!!).  It doesn't state whether those outliers were other than chronic phase, or if they had additional chromosomal abnormalities.
  
• With that said, if PB FISH is < 10%, then BM CTG & BM FISH are also going to be < 10%.  And PB FISH and BM FISH correlate extremely well to each other (only a few bizarre outliers).
  
• PB PCR vs. BM PCR appear to have less outliers ... in my review of the summary data, PB PCR looks to be a very solid monitoring method as compared to BM PCR.
  
• Oh by the way, it estimates a significant cost savings (~ $8,500) by using PB during the first 18 months of treatment (assuming chronic phase).
  

Questions for other CML'ers:

• If treatment is proceeding optimally (or close to optimal):
  
  • Given the choice at 3, 6, 12, and 18 months to go with BMB/A or PB for your testing, which would you choose and why?
    
  • What will BMB/A buy you that PB will not?  For example: Is blast cell %-age (i.e., the indicator of disease phase) **only** able to be measured through BM CTG, or can this be done accurately through PB somehow?  My blast cell %-age from the BM CTG at dx was 0.2%, but obviously I get concerned that this percentage could be increasing without me knowing it ... and is BM CTG the *only* way to confirm this?
    

I was told that we would only do another BMB/A if the PB test results indicated a need to (e.g. loss of response, sub-optimal respons over a certain period, etc.), so I'm just trying to get comfortable with that reasoning.

I value your feedback and opinions!

[Trey]

Before CCyR I would want a BMB at the prescribed intervals.  After CCyR, use of PB is fine but depends on the Onc.  After MMR (3 log reduction) use of PB is the only thing that makes sense.

[LivingWellWithCML]

>> Before CCyR I would want a BMB at the prescribed intervals.

Why?  For my case (for example), I was 5% PB FISH @ 3 months ... and a decent chance of being 0% PB FISH for my next test.  Is that not good enough to be considered CCyR (given the strong correlation between PB and BM FISH), or is there a specific reason why you want to see 0% *specifically* from marrow?

[Trey]

You could estimate that you are very likely in CCyR (near the margin of error for the test) and skip the 6 month BMB unless the 6 month FISH shows you are not in CCyR.  The BMB shows several things that are not testable by other means.

http://community.lls.org/docs/DOC-1273

[LivingWellWithCML]

Ok Trey, thank you for your input and advice.  Everything's already lined up for my 6-month blood draw for FISH/PCR, so I'm going to review those results then decide.  Given that I was 5% PB FISH at 3 months, I am optimistic that I'm already CCyR and just don't know it yet.  And based on the study, (CCyR from PB FISH) == (CCyR from BM CTG/FISH) [highly likely].

In reading through your testing primer ... :

>>> high blast count (immature WBCs)

Can this *only* be analyzed from BM?  If, for example, I am 0% PB FISH @ 6 months and have a positive downward trend in the PB PCR ratio, is it really worth the extra cost to obtain marrow for blast count analysis?  What's the risk that blast count in the marrow could be increasing at the same time that PB FISH/PCR is rapidly decreasing?

If I asked these questions to my CML specialist, I think he'd tell me to stay away from the Internet, keep taking Gleevec daily, and come back in 6 months, LOL.

[Trey]

I provided a general answer for general consumption because you asked us "what would you do?".  But if you ask me if I think you specifically need to be concerned about anything (blasts or otherwise), or have a BMB, or have curcumin enemas, I would say "no".

But back to the general, if someone does not have a quick CCyR, it is a good practice to keep an eye on the marrow, especially early on, because It is a much better indicator of what is happeneing when things are not going smoothly.  The marrow can show a number of things that PB cannot, or else does not show very well.  If all is going smoothly, then monitoring by only using PB is low risk.

[scuba]

I want to echo Trey's comments.  The timing of your question with my case is - well - timely.

I have had a very significant drop in PCR in the last two months (2 log reduction) after struggling for a year.  The two log reductio put me into CCyR (or close to it).  My PB FISH is zero.  My FISH was a puzzle because it went to zero months ago while PCR was at 55% (intl scale) - that was a first.

The drop along with the fact that my Sprycel doseage is so low (20mg). and only started a few months ago has now caught the attention of M.D. Anderson (Dr. Cortes).

I just received an e-mail from him that he wants to see me for a bone marrow aspiration.  He wants to see what the marrow is doing to help explain the sudden drop.

(Trey:  He also wants to talk to me about Curcumin!! - wants now to track it very closely - brand, type, how much, etc. and give to his research team (I was surprised))

He feels that the bone marrow will tell him what he needs to know.  PB is not sufficient given the nature of my change.  (blasts?)

The good news is that he doesn't want to do this until early November - even though I am due in October for my 3 month PCR.   But I am going to be scheduled for a full workup (i.e. that means I have to talk to his interns and research teams - this is an ALL DAY AFFAIR) to establish a new baseline.

Dan:  I would love to get a copy of that paper?