23 replies to this topic

[LivingWellWithCML]

Hey all,

I had a good 12-month follow-up with Dr. H. Khoury at Emory Winship yesterday - I've been fortunate to have a recognized CML specialist in my back yard and I'm continuing to work on building trust under his guidance and care.  The only issue I'm having at this point is that he's very big picture and I'm insanely detail-oriented, so we politely clash a bit in our appointments when I ask questions that he really doesn't think I need to be asking.  Anyway, we had the following Q&A that left me puzzled as I walked out; just wanted to get thoughts/reaction from other CMLers given that we're all seeing different docs with varying levels of knowledge and experience.  BTW, I am so incredibly grateful for Dr. Khoury and he tries very hard to get me out of the weeds and to see the big picture.  Oh, and he's a runner as well - so we have that vibe going on.  And lastly, I know that the TKI is doing the real work here, so all of this really is just me wanting to know/validate everything I've learned about CML.  Anyway, some interesting Q&A follows:

Thoughts on PCRU(ness) and dosage reduction

Me: What's the max log reduction that your PCR test can reliably detect?

Doc: Not exactly sure, but we aren't on IS and we use our own baseline.  You're undetectable through our PCR, and that's what we care about.

Me: Yeah, but is it -3.0, -4.0, -4.5?  Doesn't that matter?

Doc: Don't worry about it ... won't change a thing.  This is a great result.  If you hold this response, then we will reduce or stop Gleevec all together in April 2014.

Me: Really?

Doc: Yes.  I have a patient who stopped Gleevec and is still undetectable after 1.5 years.

(My commentary: He was pretty matter-of-fact about PCR sensitivity and dosage reduction/elimination.  He said multiple times that I should consider myself operationally cured given the test results, but aren't there still a few million Ph+ cells swimming around waiting to bump into each other and potentially cause problems/mutations, etc.?  And what about the CML stem cells causing this mess in the first place?  How should I realistically think about the status of bone marrow at this point?)

Thoughts on speed of response

Me: So, my understanding is that 12-month undetectable on standard-dose Gleevec isn't common, so I'm really just getting lucky that the first-gen therapy happens to be working for me ... this is seen more often with Tasigna and Sprycel.  Correct?

Doc: Actually, 70% of my patients who started on Gleevec made it to undetectable by 12 months.

Me: Huh?  That's counter to everything I've learned over the past year.

Doc: It's a very expected result. [Smiling at me to let me know that HE's the hematologist/researcher, not I.]

(My commentary: This stat did not sound correct to me at all and left me very confused.  NCCN guidelines state that optimal response is CCyR by 18 months [where dosage increases are recommended protocol if not CCyR by that point].  If that is defined as optimal, then how could 70% of his cases far exceed that optimal expectation by reaching PCRU on first-gen?  It just sounded wrong and I was worried that he was saying that to keep me confident that "this is usually how it goes, even on Gleevec".  Has anyone ever heard of a stat like this?  Now I'm wondering if he was thinking specifically of CCyR when he made that statement, because he has told me on multiple occasions that CCyR is *really* what matters in terms of event and progression-free survival, not MMR.)

Side Effects and Gleevec "holidays"

Me: So, I have this lower abdomen pain - it's a bit of a mystery.  Do you think it could be caused by Gleevec?

Doc: We hear about so many potential side effects, so we just aren't exactly sure.  Let's stop Gleevec for 4 days and see if it goes away.  That will help us rule it out.

Me: Uhhhhhhhhh, that sounds very scary to me.  I'm not comfortable taking 4 days off from Gleevec.

Doc: It's not a big deal given your response.  We do it with patients all the time.

[After further discussion, we decided not to do this - because I think there's a different root cause.]

(My commentary: I didn't realize that short Gleevec holidays could be done in such a matter-of-fact way over the first couple of years, regardless of response.  Frankly, I'm scared silly to skip a dose, no matter what the side effects are.  Is this really safe to do?)

Do others have similar interactions and have received similar guidance?

Thanks for your feedback...

[valiantchong]

The doctor is right on skipping one or few dosses after achieving CMR. It does not matter as half life of Gleevec is about 18 hours I believe, meaning leaving 50% or less Imatinib in your blood after a day or so... So you are still safe...

Well base on your Q and A with your doctor I guess he is a very optimistic on your progress or whoever that had achieved CCR after a year, I think he is on the group of doctor believing operational cure is actually achieved after achieving CMR after sometime. Since we do not have any way to vailidate his patients statistic records, but 70% achieving CMR in 12 months is too good to be true base on present ELN or Norvatis findings...I do hope it is the truth...

Well I kinda agree with the doctor on the mutation theory that it will not happen after easily and once you achieved CMR I think one will be fine and mutation will not happen, since there is no known report that CML will mutate that easily. If it does we will have lots of reports stating patient lost their reponse after a few years on medication but none of these actually happen. I believe only 1 or 2 cases may progress, but it is not significant.

I do not know why your doc so optimistic about stopping the medication in April, since there is reports stating 60% of the patient has reoccurance of CML... I do not think that is a good move..however no one knows unless there is more patients are able to do that... but not present.

[Trey]

He seems to be a Hematologist-Optimologist.  Very sunny side up.  Most people probably prefer this approach.  But we here at the Institute for OCD-R-US do not accept that premise.

I think the only way 70% of his patients reached PCRU on Gleevec in under 12 months are: 1) the PCR runs on moonshine reageants, 2) he has only two patients and you are counted as 70% of the two (maybe the other one is small?), 3) he has many patients but poor math skills.

The thingy about stopping TKI drugs in 2014 was unexpected.  He has 1 other patient who stopped TKI drugs and has not relapsed (so 100% of his patients have not relapsed). 

But overall, he is a good Onc and is correct that you are doing well and should not worry about it.  Good advice.

Just a reminder.  The #1 PCR maker in the world has this warning on their  machines:

"For life science research only.  Not for use in diagnostic procedures."

[pamsouth]

Trey was wondering about;

>>But we here at the Institute for OCD-R-US <<  What does  OCD-R-US, STAND FOR??

PAMSOUTH

[Happycat]

Pam - OCD = obsessive compulsive disorder

[pamsouth]

Trey,

Sorry I am assuming that is sort of a joke then, OCD INSTITUE.

OH, I GET IT, A LITTLE SLOW TODAY.  Here I was thinking you actually worked there.  I guess i'm OCD for taking things so literally.

PAMS

[Happycat]

Dan,

If you really want to know the log reduction cutoff for PCRU for that lab, contact the lab.  They would know how sensitive are their instruments. 

My onc is somewhat like that.  He assumes most people don't know and wouldn't understand the math and/or science behind the measurements and treatments, which probably is true for the majority of his patients.  Then there's that subset of patients that wants to delve into it and have done their homework.  I imagine we must be uncomfortable for them.  It kinda reminds me when I was TA'ing chemistry labs and I would get some kid who would ask me a really basic question like, "Okay, so it dissolves, but WHY does it dissolve?"   I'd have to scramble quickly for an answer that sounded better than "because it does".  I have to admit, those kids really made me think.  You really have to learn your stuff when you have to explain it to someone else.  I think some docs just don't like having to explain, or don't know just how far they can go before they lose you.  My onc keeps saying, "I don't normally go into this, but since you're in the sciences..."  He remembers my dh is working on a leukemia project at a research institute, so I get a little street cred with him.

Traci

[LivingWellWithCML]

Ok, this is helpful - thanks everyone.  We really do clash from that perspective, because I'm all about the gory details and he's very big picture.  At one point, it was a little funny cause we were discussing the abdomen pain and whether to take a Gleevec break to evaluate, and he got on a whiteboard and drew this simple little flowchart (take break for 4 days. if gone, then resume Gleevec.  If not gone yet, re-evaluate, etc.).  I was watching him draw this and thinking "Hey man, I have a degree in aerospace engineering.  You don't need to draw this funny flow chart to explain to me what a 4 day Gleevec break means". LOL, but his intentions are very good though.  I've got a friend on our street who is a professor of microbiology at Emory, and he was cool because he came over to the house one afternoon and we geeked out about PCR testing methods and such in detail, so I think I'll see if he can put me in touch with the lab so I can get the specifics.  This guy actually has a PCR machine on his desk.  Heck, I'm still bugged by the fact that their housekeeping gene is outdated ... guess it's probably used more for life sciences research than treatment monitoring.

On another note, before he erased the whiteboard, there was a bunch of stuff drawn up about ALL from a previous appointment - whewwwwwwwww .............. didn't like seeing that and was thankful that the whiteboard scribbling didn't pertain to me.  I'll take the silly Gleevec flowchart any day of the week.

I would be proud to join the Institute for OCD-R-US ... I think I'm probably a good fit ...

[Pin]

Hey Dan,

Wow - so interesting! So does this mean he wants to you try stopping Gleevec after one year of being undetectable? I wonder if that has to do with the speed of your response? I also need to consider stopping, but for the "potentially want to have a baby" reason - my doctor said she would prefer it if we waited 2 years though. I am the same as you though, not too keen on stopping something I know is saving my life, and what if it alters my overall response/future response...etc...Do I need to apply for a position at the OCD-R-US, or do they just hand them out to people like us   Hmm, anyway I will be very interested if you do try this!

Also 70% at PCRU at 12 months would surprise me - I can see why you thought he must have meant CCyR - I think that is the approximately figure for Gleevec.

My only problem with stopping for a few days to evaluate the stomach pain is that sometimes I don't get it for days, so it would not be a definitive test unless I could go without for at least a month. Did you decide yours was a stress-related thing? I think that's what mine is, I'm almost sure it comes on when I have something stressful to do at work - which I don't have a problem with as I have dealt with this type of stress-related pain before (costochondritis) but my issue is that I am concerned it is causing the other problem (the UTI). My other doctor said it wasn't possible to have a UTI without bacteria (is this even true?), but I really don't think that is the problem at all, it certainly has never been in the past, and my white cell counts have been well normal for months too. Hmm....perhaps need to avoid stressing to get rid of it?

Cheers,

Pin.

[LivingWellWithCML]

Hey Pin,

No - I believe he's following the 2+ year approach, because he's saying we could look at dosage reduction/elimination if I can stay PCRU until April 2014.  I'm not counting on it, however...many who achieve PCRU quickly do bounce in and out of detection, so I'm setting realistic expectations for myself.  But if I am lucky enough to hold this response for two years, then I will definitely consider moving to a maintenance dose (200mg Gleevec) like Trey has done.  But stopping all together?  I honestly think I'd have too much anxiety about it, but ask me again in a couple of years.  My guess is that Dr. Khoury would want to press any patient for that option, because of research reasons.....more "stop TKI cases" for him to have under his belt.

He's super big picture, so yeah - I really think he was talking about 70% achieving CCyR by one year ... much more realistic.

And YES YES on the abdomen pain -- same here!  After thinking back over year-one, I now believe the root cause is anxiety and stress that was pushed over the edge from the CML diagnosis and the reality of living with this disease and the ongoing threat of progression.  I've always thrived on stress as part of my daily living -- it's just how I'm wired -- but I now believe that CML has piled it on to the point that my anxious brain is causing some type of random swelling that ultimately causes the pain.  And when I calm down, it goes away.  Incredible.  Some notes on this as we continue to compare our situations (probably TMI, but let me know if this is helpful):

• I've had three official bouts lower-right abdomen pain since starting Gleevec in April 2011.  Each bout lasts ~ 1 month, and although I've gone on 10-15 days of antibiotics each time, I don't believe that's the solution.  I do not believe it's a urological infection at all, because I don't have the typical symptoms of real prostatitis or a UTI, and all tests are negative for infection.  I just happen to have pain in a discouraging area that gets worse when my bladder starts filling up, so naturally a urologist will assume that it's maybe a UTI or (for guys) an inflamed prostate.
• The pain completely disappears while I'm exercising (running or swimming).  I believe this is because my mind is calm and the chemicals in the brain are stabilizing ........ I'm always in a wonderful place and at peace when I'm in the middle of a good outdoor run.  I noted this to a well-respected urologist a few weeks ago and he had never heard of exercise resolving prostatitis symptoms ... and this guy is quite reputable and people travel from all over the country to seek him out for resolution to difficult urological issues.  And he's never heard of this happening?  Ok, sorry - it's not prostatitis.  No more antibiotics ... it's not the solution.  I'm going to cancel my follow-up appointment with him.  I'll go back to him when I start passing kidney stones. <ouch>
• My most recent bout has been particularly frustrating, because a 15-day course of Bactrim DS and Doxycycline didn't resolve the issue .... but over this period of time, I've been under unusually high levels of stress professionally.  Lots of client travel around the country, always having to be at the top of my game, etc.  Travel has settled down a little bit over the past couple of weeks, and the pain has become less intense.  Coincidence?  I don't think so.
• BTW, it's not like I'm running around with my arms in the air in some panic and yelling about the sky falling or anything.  This is a deep, fundamental thinking issue in the brain ... just a low, constant "I have CML, crap I have CML, why me?" thought that always seems to mull around in the forefront ... even though I might not feel overly anxious at all.  I think that anxiety situations are very complex and present themselves in very different ways.
• Under careful consult with my hematologist, I'm trying a mild course of an anti-anxiety med to see if it helps.... and wouldn't you know it?  On day 2, the pain has all but vanished.  Wow.  Oh, and I'm going to go for a run after I write this post (after I take some Naproxen to keep my left foot feeling good), so that I can continue to help resolve the situation using natural methods that settle my mind.  Given how quickly my body responded to the med, I believe that deep anxiety in the brain is the root cause.  I really do wonder if other CMLers deal with this at all, because I don't hear much about it on the board.  But the hematologist and his nurse told me that their other CML patients deal with this as well - even though we're healthy and able to live our lives with an excellent prognosis.
• I've read a lot about anxiety and how it can cause strange unexplainable abdomen pain (for guys, anyway), and there are guys out there that were diagnosed with prostatitis but were able to resolve their symptoms with Clonazepam (anti-anxiety med) rather than antibiotics.  That really got me thinking.

Anyway, that's where I'm at ........ Pin, I am calmed a bit to know that this resonates with you (and that I'm not the only one potentially dealing with this).  Are there others on the board that are dealing with this as well, or have folks in chronic phase generally been able to settle in, listen to their oncs, throw their good test results aside with a sigh of relief and live life without CML constantly in the forefront?  Although I function at a high level personally, professionally, and athletically, this is a challenge that I continue to deal with.

[CallMeLucky]

To a point you made in the conversation, if their sensitivity is not that good and they only go to a 3 log reduction, then that would mean all their MMR patients are consider PCRU, that might explain the higher percentage rate.  Not to be cynical but think about the marketing - "come to Emory where we get more CML patients to CMR then anywhere else *disclaimer, we only look to the level that satisfies our claims." LOL

I have found that just because an Oncologist is a CML expert and could be quite brilliant, it doesn't necessarily make them a mathematician.  PCRs are complicated and I don't think they care enough to get into the details because the details don't matter.  We obsess because we have the disease, they look at trends and broad stokes.  They don't care about variations in the test.

[LivingWellWithCML]

I think you nailed it, Lucky - fortunately, my calculations seem to point to -4.0 log reduction sensitivity, which is definitely more settling than -3.0 sensitivity.  I wish it were more like -5.0, but I feel it's a good trade-off to make sure that I'm getting PCR testing done on-site vs. having the blood sample shipped out to degrade en route.

I have an oncologist that's closer to my house who ships blood out to Genzyme.  I wonder what their PCR sensitivity is?  I had one FISH test done through Genzyme and they only analyze 200 cells (vs. 500 cells, which would be ideal.  And Emory's FISH test only analyzes 200 cells as well).  Guess I could always consider a once/year trip to Portland to see Dr. Druker or Mauro ... their machines (from what I understand) are some of the most sensitive around.

Yes, I agonize over this stuff when I really shouldn't...

[Susan61]

Hi Dan:  Let me share my history of Gleevec.  I started on my Gleevec 400mg in Oct. of 2000.  I achieved my CCYR at  6 months.  Then I got to PCRU in 2003 with a reading of 0.000 which is a 5 log reduction according to my lab.  I have maintained this for 9 years this past January.

    As far as stopping the Gleevec totally, I do not agree. My numbers are dropping and out of wack with my latest test results.  My Oncologist is leaving everything alone until my next test in July, then I may have to cut back my dose to bring those numbers back up.  I am even thinking she might put me on a Gleevec vacation to see how I do if they are really low.

   Your doctor does sound like he feels you are doing good, so just leave it alone.  I do not agree with the stopping the Gleevec in 2014, but thats just my opinion.  Then again who knows what more we will have learned in the next 2 years.

   I do think you are doing very well though.  May you continue on with good results.

[Lori's okay]

Bravo, Trey!!!

Thanks for the shot of laughter endorphins!!!!

[Sneezy12]

What numbers are dropping? Frank

[Pin]

Oops! I must have read the dates wrong (or I am a year ahead of myself!!). That will roughly be my date for potentially stopping too, as long as my next test actually comes back as undetected of course...

Very interesting indeed - I hope your response to the anxiety meds continues, is this a short-term experiment though? Most anti-anxiety meds are designed to be used short-term (with the exception of anti-depressants I think). I will have to try this myself as I'm almost sure that the pain is caused by anxiety. What is complicating in my situation is that I have actually had UT infections! I do wonder if it is just a coincidence though, the ER doctor I saw thought that the first course of antibiotics was unlikely to have been effective and that the second was just the previous one relapsing. I'm wondering if the infection may have started back when my white counts were a little low, and all this is just a coincidence designed to red herring me!

I also find that it goes away during exercise - except when the sport is the cause of my anxiety! But that's another story....Anyway, it's great that we can actually share stories, and at least console with each other that we are not alone with what may prove to be a very uncommon side effect!

[Sneezy12]

Have you had a complete G-I evaluation, including a Colonoscopy, Endoscopy and CT of your abdomen? Frank

[LivingWellWithCML]

Good question on the term.  I don't know yet.  All I can say is that I've started a mild course and so far ... the pain/pressure has basically vanished.  And I slept last night for a full 8 hours (while on a client road trip in a hotel) ... I cannot remember the last time that I actually slept comfortably for 8 full hours!

I have not had a GI exam, but I had a CT of my abdomen last year after the first bout and there was nothing interesting going on at all.  They made a vague note of potential prostititis and found a few kidney stones (which was an interesting find ... something to look forward to there!), but the ER really just did the scan cause I was in a panic about the pain and they wanted to make sure I didn't have some obvious form of tumor/cancer lurking ... of which they found nothing.

I'm 43, so I'm due for a colonoscopy in the next couple of years (definitely before I'm 50, just to be safe).  But that is my theory ... that anxiety causes GI (not urology) issues, which ultimately causes pain/swelling low in the GI tract.  But now that the anxiety has subsided, all pain/sensation have completely gone away.  Definitely a connection.

Pin - heh, track & field in high school caused me a lot of anxiety ... especially before the 800m races.  But it made me run faster in the end.

[LivingWellWithCML]

Thanks Susan.  Your posts (and how well you've done on treatment for so long) always cheer me up.   So, you've been undetectable for so long, I'm sure that you could handle a dosage reduction for a period without any issues whatsoever...

[Susan61]

Thanks Dan:  I do have other health problems, and I have just felt so blessed to do as well as I have with the CML, and I have had people tell me to cutback on my dose which could help my blood counts, and probably make me feel better.

I think I am afraid of something going wrong, but if monitored properly I probably could take a chance.

Some people believe that if your PCRU for so long that your most likely cured, and would not have a problem.

I do not know as much as others, but I do know if you do not kill the stem cells that you can be right back where you were.  The way my doctor explained it to me awhile back was that killing the cancer cells is like cutting your grass, but the root is still under there to make more grass grow or cancer cells grow.  I am just being very cautious.

I hope to see something developed to be able to kill all the underlying cells that are still there that can cause the CML to be in full bloom again without our TKI drugs.  They are working on so many things, but I have not heard of anything conclusive to this day.  This is just my opinion and how I feel.  Just glad your doing so good.  I think its so important for all our newcomers to see the progress so many have made.