25 replies to this topic

[xxgirl]

Hello again all.

 

Diagnosed 4/2014

 

Historical meds and corresponding PCR's

 

Gleevec 400mg 4/14 - 2/15

7/22/14 - 21.36%

9/18/14 - 14.61%

10/31/14 - 10.88%

1/29/15 - 46.26%

 

Sprycel 100mg 2/15 - 7/15

4/3/15 - 24.25%

4/30/15 - 12.16%

7/2/15 - 9.84%

 

Persistant low blood counts and multiple transfusions prompted my dr to try a lowered Sprycel dose.

 

Sprycel 50mg 7/15 - 8/15

8/25/15 - 21.46%

 

Sprycel 100mg 8/15 -12/15

9/15/15 - 8.62%

11/3/15 - 8.95%

12/1/15 - 18.20%

 

Tasigna 800mg 12/15 -9/16

12/31/15 - 21.81%

1/26/16 - 12.30%

2/22/16 - 12.81%

3/7/16 - 14.2%

4/18/16 - FISH 42% PH+ (peripheral blood)

4/26/16 - 12.52%

5/26/16 - 8.98%

7/18/16 - 4.0%

 

Ponatinib 30mg 9/16 - 4/17

9/23/16 - 9.49%

11/14/16 - 5.0%**

1/11/17 - 7.79%

3/2/17 - 8%**

 

Bosutinib 500mg 4/17 - present

5/15/17 - 5.6%**

8/21/17 - 3.7%**

10/31/17 - FISH 20% PH+ (peripheral blood)

1/8/18 - 3.6%**

 

**not my usual lab

 

I've been tested for kinase mutations, and have a somewhat obscure insertion that suggests that Gleevec may not be effective.  No other mutations found.

  

A BMB performed 2/16 showed a deletion of 9q34 - what they call a "variant Philidelphia translocation".  According to lab reports this may indicate a "resistance to therapy".

 

My doctors have been pushing me towards a SCT/BMT for the past 18 months or so.  While I haven't had tremendous response, I haven't had any accelerated loss of response, either.  Yet.  My results from last week just came back essentially unchanged since last August.  So, do I keep on keeping on, just waiting for things to go bad?  (Routine blood test results all seem normal.  Thus far.) Or do I follow the advice of my doctors and proceed to transplant?  I know that this has to be a personal decision that I must make peace with, however, I've turned this over in my mind a million times, and I wonder if I'm being realistic about my prognosis, so advice would be welcome.

 

Thanks.    

 

[thatguy]

I'm so sorry for your predicament and constant fear you must have dealt with the last several years. Do you have full matches available? I'd base my decision largely on that and how comfortable I feel with doing one over the other. Keep us posted!

[Melanie]

Such a difficult situation and very sorry you're in it. Are you seeing a CML specialist? If not, I would recommend at least a second opinion from one before transplant. I found my self in a similar situation and traveled to see Dr Cortes for a 2nd opinion. We tried a few more things and they worked. Took time, over 2 years after seeing Dr Cortes and starting Bosulif, I finally had a negative fish, then reached MMR end of 2015, lost it, but got it back this last year. Although there's no way to tell if more time will work like it did for me, we're all so different. I would say get the transplant matching done if you haven't already as That Guy says and get a second opinion. When you have all the information, then you might be able to decide easier. Hope so! Take care and let us know what you decide.

[r06ue1]

You may look into a trial, ABL001 being the top on the list.  This trial (which it looks like you qualify for) is still recruiting:  

 

https://clinicaltria...recrs=ab&rank=1

 

There are a few other trials also, all of which are recruiting, but that one looks like the best fit for you.  

 

https://clinicaltria...te=&city=&dist=

 

If your current Oncologist only wants you to do transplant I would seek out a CML Specialist and discuss your situation with them:  

 

http://www.nationalc...cml-specialists

 

Dr. Druker or Dr. Cortes would be at the top of my list of recommendations based on experiences others have had with them on these forums.  

 

Transplant would be the last thing I would choose to do.  CML has a way of coming back even after a transplant in many patients and you may also have to deal with GVHD afterward.  The survival rate isn't that great either.  

 

 

 

Results of recent studies of allogeneic bone marrow transplantation for CML report long-term survival rates of 55%-80%...

 

https://www.medscape...rticle/408451_8

 

Trey may have some better information for you, he is the resident expert on these forums.  

[Trey]

There is no clear answer, only choices.  Personally, if it were me, I would hang on with the TKI drugs and would try the ABL001 clinical trial.  If that was no more effective I would wait for another new drug to come along which might work better for the longer term.  I believe you are on the younger side, so BMT/SCT is not out of the question.  But since you have not shown signs of complete relapse there does not seem to be an urgency in deciding on transplant.  So that could remain a future option if needed.  The key is you do not want to completely lose response prior to a transplant, which makes it more difficult.

 

Regarding the der 9 micro deletion (9q34) it sometimes causes lesser responses for tki drugs.  It is not part of the Philadelphia Chromosome which is chromosome 22, but rather it is part of the chromosome 9 where half of what becomes the Philadelphia Chromosome broke off.  The remaining piece of chromosome 9 (der 9) normally does not exert an influence on the CML processes, but as in your case the chromosome 9 break resulted in a deletion of a piece of material which caused the chromosome 9 to send out signals which can "inhibit" the tki drug from working as well.  Sometimes it also causes more severe anemia, as in your case.  Sometimes the der 9 9q34 deletion has no impact.  It is a matter of exactly where the micro deletion occurs.

Edited by Trey, 17 January 2018 - 10:27 AM.

[xxgirl]

Thatguy - I've been tested for matching, and there are three 10/10 unrelated donors that match in the registry.  You would think that would make things easier, but it doesn't.  Knowing that they've requested further samples from 3 people, and they have all given willingly makes me feel like a real a**hole for basically saying "nah, why don't you guys just wait around in case I need ya."  That said, the stakes are a bit higher for me than for them, so I'm willing to feel like an a**hole.  

 

Melanie - I haven't consulted with a CML expert.  Honestly, I'm not sure what they could suggest for me that I haven't already tried.  Despite my low counts that persisted for MONTHS/YEARS I continued on full dosage TKI, and my PCR numbers still went up.  I'm at a place now where my counts have stabilized in the normal/low normal range (except platelets - those little buggers are still a bit low, but not worryingly so). 

 

R06ue1 - Yes, ABL001 is still a possibility for me; but am I just prolonging the inevitable while possibly incurring considerable travel expenses, and possibly giving my disease a chance to progress?  At this point I've been on all approved TKIs, and have only moved to the next when I stopped responding and my PCR rose.  Seeing as how I've never reached any of the milestones of the NCCN, most importantly CCyR, I think that I understand the transplant risks better than most people that haven't been through one, as it's been on my radar for years now.

 

Trey - I'm 37.  I'm inclined to stick with TKI therapy as well; against all of my doctors recommendations.  But again, I wonder if I'm just prolonging the inevitable.  Its a delicate balance to try to maintain some level of response but be ever vigilant to make sure that I'm not losing response when my doctor is constantly reminding me that 3.6% is still a very high level of leukemic burden, and that blast crisis is a deep concern and possibility.  I super analyze every single blood test. I've noticed recently that while my numbers are all within range, the percentage of neutrophils is now higher than the percentage of lymphocytes.  (Is that something I should be concerned about???)

 

As awful as it sounds, I wish that my results would clearly push me one way or another.  It's gotten to the point now, every time I have a PCR test, instead of hoping that I go down, I just hope that whatever the result is, that it will help me to make a clear decision with how to proceed.  Which hasn't been happening.

 

Thanks everyone.  Your responses help me to analyze my situation better, so that I can make the best choice for me. 

[AdamJ]

Personally I think that ABL001 might be worth the trouble. It binds to a different location than existing TKIs. See http://www.clinical-...1122-9/fulltext for some scientific details.  I suspect the fact that you have tried all 5 existing TKIs might make you a good candidate for "compassionate use" even if specific trials are closed.  

 

I do know someone who had a successful SCT a couple of years ago (AML, not CML) though and things are getting back to normal for him at this point.  It was rough for him, but he is happy with the results.  As was mentioned above though, CML can always come back so even an SCT may just be postponing things. 

[r06ue1]

Thanks AdamJ, was about to mention that (ABL001 binding to a different location), from what everyone has heard or read, it has a lot less (to no) side effects also.  

[xxgirl]

AdamJ and R06ue1:

 

Valid.  

[xxgirl]

The reality of the situation is that I have to make what could be a life or death decision based on fear. 

 

What do I fear more - a stem cell transplant, or poorly controlled leukemia?  Right now a transplant is the more terrifying of the two.

 

I hope that leukemia doesn't eventually tip the scales in the other direction.  

[kat73]

xxgirl - Another thought on ABL001 is that, I think they use it along with whatever standard TKI you're on, which gives you two punches instead of one.  I believe that is the thinking behind their hope that the leukemic cell can't adjust and work around all those blocked sites at once, and just dies.

 

In making your hard decision, don't be swayed by feeling badly for the donors' having to do additional tests.  Remember, they wanted to help when they signed up - they'll do anything to help someone.  A long time ago (LONG before CML) I signed up to see if I could be a match for a friend (acquaintance, really), and if they had called me back to come in to the hospital, do more tests, give more blood, whatever - even if it never got used, or it didn't work out - I would have been more than happy to do it.  I think most potential matchers would.

[Trey]

There is no such thing as "just postponing the inevitable" when it comes to trying each of the available drugs one by one.  It only takes one to work and it may work for a lifetime.  With many drug choices, we only need one of them to work.  That is why a person should try every single one of them until they find one which works well enough or else find out there is no drug which works well enough.  In that way the choice makes itself.

 

I doubt any potential donor really wants to give up their stem cells to you.  They would probably rather just give up a little blood for testing.

 

Don't worry about cell percentages.  They often give a distorted picture because the math always forces them to add up to 100%.  And just having allergies can distort the percentages.  It is the absolute values which matter.

[thatguy]

Xx, the thing I have in common with you that others on this board may not have, is that I too was pressured towards transplant by my doctor due to my differing response levels from the normal cml population, and not in accordance with the most recent guidelines. I sought out a third opinion by Dr. Deininger who I'd consider as notable as Cortes, and maybe Druker, he's worked with Druker and helped author prominent publications and cml guidelines. I believe you're in CA, and he's in Utah. You might consider him too. My cumulative take away regarding our demographic and disease is this:

-young people tend to have more aggressive disease.
-young people typically "do better" with prognosis long term, ironically since the above would imply otherwise.
-young people with a 10/10 match (under age 40 was the limit I was told) remain in the highest percentages of successful bmt/sct survival. Which, I've been told is 80 to 90% from different dr's.
-sct/bmt is most successful at lower pcr number, and significantly less so as disease burden rises, and if phase advances especially. (Im assuming because it's more likely the chemo and radiation won't get everything). So people saying they wouldn't do it until advanced or blast phase, may do so by their choice, but shouldn't expect success, or enjoyable life to be the outcome.

We're sadly different in respect to that while fortunately Bosulif brought me where I needed to be to feel somewhat comfy with things, you've obviously exhausted every readily available tki without that success. And I can't imagine that constant fear, but I feel like I may a little better than some of the others on here.

It gets a little scary seeing people log on here and stating in their first post that they hit mmr in month 3 or 6 on Gleevec, and their next post a month later is talking about dose reduction...

I believe your wbc was over 500k at diagnosis which isn't common from what I've seen here, and in my non-trained mind suggests the disease had progressed further than most others' on here, or at least been festering longer (I've been told that my counts at diag suggest the same for me). The additional mutation is certainly a wild card, which medications aren't necessarily tailored to or designed to fit.

Figure out what you're living for if you haven't. My goal is to get my house paid for and see my youngest hit 15 at least, so I can feel that they can manage without a father figure. I've contemplated saying screw it, if I'm meant to live, I'll live, and going for transplant. Being disease free is pretty tempting to think about. But decidedly, I would do as you have and exhaust every option prior to doing so, my response coordinating with guidelines, and my balancing the rest.

Best freaking luck, honestly... I feel awful for you...but I'm not saying to feel gloomy, because transplant statistically is in your favor. Just try to have peace in your life.

[xxgirl]

Trey, I get what you're saying, but when do you "call it" as they say? Try every drug until you find one that works well enough - but what is "well enough"? No one can seem to tell me. Maybe Im at "well enough" right now but there's no way to tell until all of a sudden I'm not anymore.

My fiance asks me "What do other people in your position - people that have tried all of the TKIs and are still above 1% do?" And I have to say, I don't know. First of all there isn't anyone like me, and second of all most people don't work their way through all five due to resistance. I can only assume that after the third or so they listen to their Drs and proceed to transplant.

Thank you thatguy for your understanding. Its been really difficult living with this hanging over our heads for the past several years. Every time I get sick or get an infection, I'm sure that my disease has progressed Blast off! and I berate myself for not having anticipated it when my Dr has been warning against it for so long.

You're right, my WBC was over 500000 at diagnosis and I agree with you that I most likely had leukemia brewing for a long while before it was discovered. That's part of why I'm on here asking everyone else what I should do. To my detriment I ignored night sweats, bruising, fatigue, weight loss to the extent that you could count each vertebrae and a spleen so enlarged that they could barely see any of my other organs in my cat scan. I rationalized all of those things for possibly years, so am I rationalizing again and is it unreasonable to think that bosutinib still could work for me if I just give it a little bit longer? Or abl001? I want one to work so badly...but that hasn't been my reality. So I try to look at things objectively but that is difficult when you're afraid for your life.

Honestly, right now, I'm inclined to give myself a deadline and postpone transplant for a finite amount of time and see if continued drug therapy can get me to a place that both myself and my Drs feel more comfortable with. Which is ultimately what I've been doing all along.

More of the same. Carry on.

[chriskuo]

I think you should give Bosulif more time while you investigate the ABL001 trial.

In your situation, I would also consult with one of the very top experts and not rely on just a local doctor.

[rct]

I am sorry you are in this mess xxgirl.

 

You wrote:

 

Try every drug until you find one that works well enough - but what is "well enough"? 

 

If he is still working, Druker will probably say that getting the same numbers, or in the ballpark, as everyone else is not getting "good enough".  "Good enough" is relative, for everyone.  We went from one ocean to the other to see him, 7 years ago.  While we and the east coast oncs at some pretty well known medical/education centers were pretty scared, he wasn't, he thought that Mrs was doing pretty well.  We stuck with his advice and stuck it out, she is still here and still making her way to retirement.  If we followed advice from some pretty smart folks we would have gone back out there to Hutch for a transplant, the only place really to do it if you want even a modest chance of success.  All of this while she was PCRu for 4 years by that time.  All because they couldn't figure out her counts and why they were not the same as everyone elses.

 

The point for him was not a number to indicate control, but a state of person.  Mrs hasn't had an ANC above 1000 for over a decade now.  They are at a complete loss as to why, and they have all acknowledged that maybe that number we seek for "normal" isn't really all that important after all.  Decent blood counts and some form of control over CML may just be what will end up as "normal" for you, just as Mrs just had tooth surgery yesterday with an ANC of only 800, and nobody worried about it at all, it's her "normal".

 

Good luck.  I hope a trial can find better numbers for you.  I hope an oncologist not still invested in transplants can be found, one that will work with you to change dosages and try to find the right spot for your "normal".

 

rct

[xxgirl]

Chriskuo - While its true that I'm not seeing one of the top five, I am seeing a doctor at UCLA who is very smart. While my dr has suggested that due to my response I go to transplant, they have been respecting my wishes to try all available options before I do so.  They don't currently have a trial at UCLA for ABL001, so we haven't talked about the possibility of that much yet. 

 

Again, I've considered requesting a consultation with another doctor and another facility, but to what end?  Keep seeking answers until someone gives you the one that you want to hear?  I feel like they can only offer suggestions based on their knowledge and experience...which is how the current guidelines for CML were created.  And based on those, transplant or a trial are my only options at this point.

 

Thank you for your perspective RCT.  I know that your wife has been dealing with low counts for - what  - nearly a decade now?  I think that you're very right to point out that while several doctors didn't know what to make of her persistent low counts coupled with PCRU, that it was very wise to look at her case holistically. 

 

If you do that in my case, and take into account "all things", my blood counts have normalized, I've achieved the lowest PCR result that I've ever had, I work 40+ hours a week and lead a normal life aside from the emotional roller coaster that I feel like I'm on every time I see a doctor.  So are those results "good enough" or "well enough"?  For now, I'm inclined to think so, but the truth of the matter is that IF something goes bad with my blood, I'm just about out of options.  I'm the sort that likes to have a plan in place.  

[thatguy]

Xx, since my last post went on so far, i forgot to mention that the Bosulif does show a decline over time, that maybe will continue and get you to ccyr over the next few months. If you choose to ride it longer, use the same lab..then pick the same day of the week to test, same testing time and consume plenty of liquid prior to. And maybe avoid high fiber foods, within hours of taking the pill, and I even feel milk might be wise to skip too, based on my result fluctuations (and maybe overanalyzing?). If you get an increase result, test again immediately to verify. If possible get pcrs drawn the same day at 2 separate labs to see variations present, and gain some rightful peace of mind possibly. I've done all this and it helped me feel more in the know.

[JohnFromChicago]

xxgirl - I was also diagnosed at a young age (28). The first local doctor I saw prescribed me 300mg ONCE daily Tasigna. At first I thought the best method to cope with the diagnosis was to just take the pill and forget about it. Thankfully my OCD self caught his error after thoroughly reading the entire Tasigna RX insert and I immediately dismissed everything he had told me. I researched CML day and night for about 5 days straight. I flew out to Texas and went and saw Dr. Kantarjian at MD Anderson. Although he only verified what I had already learned from my many hours of research it was nice to have the extra confidence I was doing the right thing considering my young age. If I were in your shoes I would definitely try to meet with him or one of the other CML experts at MD Anderson. Their team could really look at your whole picture and give you the best gameplan. Im guessing and hoping for you that they say ABL001, but always nice to have the extra confidence from an expert team.

 

thatguy - I have also been thinking for a long time now that it seems younger people tend to have a more aggressive form of CML. I actually brought it up on a here a while ago but was kind of dismissed with my theory. This is just based on everyone's PCR trends in the forum. It seems that anyone diagnosed under the age 30 rarely reaches MMR in a year. Im sure there are a few outliers but it seems that the % of people reaching MMR in a year diagnosed above 30 is way greater than those under 30. It is nice to know that research shows our prognosis is still good regardless of this. Do you have any links to the research?

[xxgirl]

Thatguy -  Got it. I'll make sure that I'm there on a Monday morning, wearing my lucky socks, after my breakfast of powerade and a bag of beef jerky.  Kidding.  But really, how can people give so much credence to a test that could be swayed by seeimngly superficial influences?  Maybe PCR isn't as precise and shouldn't hold as much weight as my doctors and I have given it?  Just a thought.

 

JohnFromChicago - Thank you for including me in the "young" group.  I was 33 at diagnosis, and certainly felt young and stupid when I got blindsided by this.  Will be looking into ABL001, so we shall see on that front.  

 

Again, thanks everyone.  It's good to have such a diverse group of people to be able to bounce ideas off of.