36 replies to this topic

[rct]

scuba wrote:
I am very puzzled that the CML specialists, when faced with myelosuppression in their patients, keep trying the high dose's with drug interuption rather than go the other way and see if response stabilizes at a low dose and then work up.

There is a great need to prevent myelosuppression from becoming "side effect".  It's side effectiveness could render TKI not approved.  It's why they try to call myelosuppression "an unfortunate consequence" of having CML and using TKIs, which actually makes your head hurt if you think about it too long.  Espcially when people gain two pounds and the docs immediately change drugs and are pulling their hair out to solve this medical mystery, while people suffering through neupogen and the now other unknown leukemic world of chronic, apparent lifetime low anc get "unfortunate consequence" and that's just too bad.

That's my experience so far with my Mrs.  I don't have evidence from anyone else to demonstrate any other conclusions.  If anyone has some, please put it up here.  Don't just call me a bitter kook without some explanation.

rct

[pamsouth]

Phil, Scuba, RCT, 

THANK YOU, THANK YOU, THANK YOU!!  I have been looking for the words to put this in persective.

Great Job!!!  I will copy, paste and save to a file!!!!  I was beginning to think I had lost my mind!!!

This may be a poor attitude on my part, but after 6 1/2 years and much reading and understanding to a certain level that I can.  I have begun to wonder about many onc view of hit hard/ fall fast and hard, then move to bigger dose, new med, old med, up/down. suffer...  It just made no sense to me, unless they want to keep you coming back for more money or strictly the research, (sorry that wasn't nice of me)  I have been at a few seminars where there are some onc, who would disagree with the hit hard and fast.  Who knows when you get on so many meds what all these chemical, do or the outcome. There are no guarantees if you are MMR that you will not have a mutation or something will not go wrong, maybe a slight change more at CCYR, but there are some oldies holding on the edge of CCyR for a few years and are stable, and are having a better quality of life with out continualy suffering anymore side effects then they have to with messed up CBC and low counts and the hit your organs may take, especially as you get older.

PamSouth

PamSouth

[Melanie]

Thank you. I'm going to present these same thoughts to my onc today and see if he will listen.  He may still be under the belief system that unless you're on the full dosage there can be no response. I'm praying he's willing to use his great expertise and try something off the normal guidelines. Here's to open minds!

Melanie

[Melanie]

Scuba, I was on the treatment of drug interruption and modification for some time. I would prefer this option.  My onc got nervous because of length of recovery time and the increase in basophils. (up into the 20's)  That's when he thought my only option was BMT. My BMT Dr disagreed and wanted me to try the TKI's again, with low dosage and gradual increase, and tough out the low ANC and supplement with Neupogen if absolutely neccesary. That's where we are now. We'll see what my Dr says today as what is plans are. I'm praying he'll measure response now on the lower dosage and let the results determine the future treatment plan. We'll see. Thanks for your imput!

Melanie

[CallMeLucky]

Many oncologists have an "old school" mentality about this stuff.  Targeted therapy like Gleevec is relatively new and hasn't been around long enough.  Unless your doctor really studies CML and is up to date on the latest they may not have the confidence to say "sure let's try a lower dose and see what happens".  With most cancers when you do that, the cancer spreads and you lose the patient.  The conventional wisdom is hit it fast, hit it hard, and don't stop hitting it until it is obliterated.  Complicate things by the fact that CML is not exactly like other cancers, particularly in the chronic phase and this gets even more complicated.  Even within CML experts there are differing opinions.  My doctor is a CML specialist working at one of the top cancer centers in the world.  When I brought up dose reduction she told me I would have to find another doctor if I wanted to do it because she would not even entertain the thought of it.  I know she is conservative, but I also respect her experience and while I am intrigued by some doctors willingness to go off label and see what happens, I keep in mind 100% of the time that when a doctor takes a chance on something it is really we the patients who are taking the risk.  Anyone who tells you that using TKI below what has been tested in a trial is perfectly reasonable and safe is not being fair to you.  They can't know that, just like they can't tell you what your outcome will be if you do everything by the book.  Everyone reacts differently.  If one person takes low dose and develops resistance that leads to an unfavorable outcome would that mean that no one should ever go low dose?  Would it mean the low dose was the cause of the resistance or would they have had trouble on full dose?  This is very tricky stuff and until someone perfects the crystal ball you are taking a chance no matter what you do.  I think most doctors want to take the safer route and hit it fast, hit it hard.  Of course they are not the ones living with the side effects.  You have to determine what your level of risk is and then find a doctor that has a similar level of risk tolerance and then proceed from there.  There are no guaranteed outcomes, what works for one may be highly unfavorable to another. 

[CallMeLucky]

"We'll see what my Dr says today as what is plans are. I'm praying he'll measure response now on the lower dosage and let the results determine the future treatment plan. We'll see."

Remember Melanie, ultimately it is up to you - if you don't feel comfortable with the direction your doctor is taking you, then find another doctor. 

[Tedsey]

Re: Since the CML stem cell creates leukemic white cells and doesn't listen to the shut off call from the normal stem cell, does that mean that the neutrophils, esonophils, and basophils that do show up could be leukemic and not working at their best?

Melanie,

As I understand it, the leukemic stem cell, (LSC) doesn't "listen" to the "shut off call" from the healthy stem cell.  It works independently.  I think what happens is that because the LSC makes leukemic WBC that continue to proliferate, the healthy stem cells cease or slow down production of healthy WBC.  The healthy stem cell receives a signal to stop reproducing because there is already enough WBC (although, leukemic).  So, the healthy cells stop dividing and the leukemic ones keep on going.  The TKIs plug into the space on the leukemic cells, and if it works effectively, it keeps them from dividing at all levels (but mostly lower).  Thus, it causes apoptosis in the leukemic cells.  This cuts the number of leukemic WBC down so the healthy stem cells are signaled to repopulate with healthy WBC.  Ideally, the healthy WBC eventually replace the leukemic ones.  However, the LSC are very clever (as Trey says).  It is believed they can change the environment in the bone marrow (as pointed out by Lucky), so it is easier for them to hide.  They may even go into a state to quiescence (sleep; so to speak), until there is a chance for them to come out again and reproduce.  But if the drug is ever-present, they may eventually die or get nailed (using Michael's term) by the TKI when they start to divide again.

This is as I understand it.  I welcome anyone who wants to correct me.  It is a very complex subject for me.  I feel it is important to understand the intricacies.

I am so glad to hear your latest CBC was so good.  You PLT are low, but OK.  Just no contact sports.  I was a Neupogen and Aranesp taker soon after taking a TKI.  So, if you have any questions, don't hesitate to ask. 

I am on Sprycel now, and it has taken a year and a half for my counts to climb back to near normal.  My PLT are still low, and I am close to MMR.  Nevertheless, I have never had a dose reduction on Sprycel, even when my counts were really in the doghouse.  But I was allowed to ride with lowish counts because my onc knew how I hated the Neupogen, et. al. (stim drugs), and they are risky.  My onc says the issues with WBC and the PLT are due to the disease and not the Sprycel or dose (makes me think of RCT and what he said about why low counts are not considered a serious side-effect).  Of course, that is her opinion.  However, I choose to stay the course on a full dose because I have almost no side effects (except awful mouth sores).  And I am not officially MMR after 1 1/2 years on Spycel (I was dx 2 1/2 years ago).  I consider my onc very good.  She is conservative, but I feel she really wants me to survive.  I really believe she wants to do what she thinks is best for me.  The comment by your onc that he didn't want to tell you the FISH results because they would "depress" you is goofy.  Esp. if you wanted to know.  We have to roll with the punches with this disease.  But most of the news we hear will be good.  Here is to continued healing to you and normal counts!  Wish I could help you more regarding your "anyone on a reduced dose" question.  I am on a different course (full dose, due or die), but I have experience with low counts.

Teds       

[rct]

Tedsey wrote:

My onc says the issues with WBC and the PLT are due to the disease and not the Sprycel or dose (makes me think of RCT and what he said about why low counts are not considered a serious side-effect).
 
    

Indeed.  And in the name of everyone suffering with this, we have offered clearly to go off any TKI and see what happens.  One of  us will be right, right?  Counts will stay low because of disease, or come back up because of the missing drug, right?  Silence.  Unfortunately we need medical care from them, regardless of the level of the courage of their convictions.

It is our belief after 4 years of this low counts thing, that there is far more to CML than just white cells that refuse to respond to their normal life span, and that for many there is a fundamental damage done or flaw in the marrow, the factory making this stuff.  But that would make the miracle drugs much less miraculous, so our ideas and more importantly our experience is not welcome.  Best to have those that are doing great keep doing great and be the loudest.  It works for everything else, so medicine too.

rct

[CallMeLucky]

I agree RCT and it may be a factor in how long the disease is in the system before treatment starts or perhaps other factors that we do not know about.  There was a study done by the researchers at City of Hope that showed how LSC alter the bone marrow.

http://www.cityofhop...and-return.aspx

http://www.youtube.c...h?v=ce58rAMvKZQ

[rct]

CallMeLucky wrote:
I agree RCT and it may be a factor in how long the disease is in the system before treatment starts or perhaps other factors that we do not know about.  There was a study done by the researchers at City of Hope that showed how LSC alter the bone marrow.
http://www.cityofhop...and-return.aspx

Honestly Luck, our belief is that we, the imperial we, know less than about 12% of what is going on with this.  The initial blush of headwarming Gleevec Koolaid is sorta fading, and we're getting left with...hangover I guess.

rct

[pamsouth]

Scuba, Dr. Cores sounds like he knows what he is doing, where is he located. I purchased some turmeric with 95 % Curcuminoids.  Is this what you have have been talking about?

PamSouth

[pamsouth]

Mbrown, I was at a seminar back in maybe 2006, one of the leading Leukemia Specialist in my area was one of the speakers.  He has probably been a leukemia specialist for over 30 years.  I will never forget when he said in the old days we were taught to hit the cancer patient hard and fast with drugs and we actually killed them before the cancer did, but that was what we were taught.  I have never forgot that.  Just my theory, sometimes I think the doctors are taught a lot from the makers of the drug companies. Push the drugs.    Not that they don't save lives but maybe we overdose patients.  I think that many of us want a drug for everything, a fast cure, when in some situations we can live without overmedicated ourselves. just some common sense.  A couple of years the doctor about killed my husband with arthritis med he was allergic to.  They just kept giving him more medicine, pain pills, neurotic, predisone, etc.  He kept getting worse, he was so swollen he couldn't feed himself, dress or bath, couldn't hold his head up and I can barely get him into the car. I kept taking him to so many doctors, as his CBC and labs were a mess, I even thought he had cancer as his Eosinophils were off and his mother had died of Luekemia in 1962 at the age of 42 years.  Yea seem odd that his wife would be diagnosed with Leukemia too, kind of a shock for him as he watched his mother died and now his wife, he didn't know what to think.  Finally I said Larry we need to ween you off this medicine.  In a few weeks the swelling went down and he went to physical therapy.  He has been working part time for a year now.  He still has arthritis but he doesn't take anything for it he just lives with it.  He was allergic to the maloxacam (something like that) a generic of Mobic.  I couldn't get a doctor to take him off of it, but I was almost to the point of sending my husband to the nursing home. So against all the doctors I did what was in my gut and it had a good ending.  Sometimes you have to be your own advocate when things to feel right.

PamSouth

[Melanie]

Hi everyone, just wanted to report what my Onc decided today. Open a bottle of wine and let's have a toast! Although I got him to admit he is old school and believes in hitting hard and early, he was open to what was being said here.  He left my dosage at 450 and lowered the shots to 5 a week. He's also ordering a Fish test for next week to see if I'm having any good response. These were all things I had wanted, so I'm praying the results are good. He is worried about my low platelets and ordered some extra test for that. He believes that's the CML. He's always been pushing for a BMT since my first go around with the TKIs didn't work, but is willing to try this approach even though he feels it may be wrong. He also had talked to another visiting CML specialist that works in France about my case and he too suggested a BMT. Really??? Regardless, thanks for all the dicussion. It's been refreshing and empowering. We'll see what next week's numbers bring. Blessing to you all!

Melanie

[pamsouth]

Call Me Lucky,

I have  printed Treys article on "Genetics of CML Leukemia Overview" and studied it in detail.

I have also listened to the video you posted and read the article from the City of Hope. 

Seems you can dig and dig and come up with more questions/speculation/theories then answers. I do definitely think we have only skimmed the surface.

One of the most important question that come to my mind is the mutations, and the level of response to TKI drugs?

If in fact TKI drugs fail, to kill the actual primitive leukemia cells where it all starts, then these CML STEM CELLS  are even more cunning and powerful villains in the CML story then once believed. If in fact the primitive leukemia cells, actually transforms the microenvironment of the bone marrow or neighborhood, to give themselves, a protected place, to hide and grow.  Brings me to this question; then at what level from the top, do the mutations actually occur ????  If the mutations actually occurs at the top of the genealogy or the primitive stem cells (which the TKI drugs never get to) then it doesn't matter what level of response we get to, taking the TKI drugs, because the mutation is at the top of the chain where CML starts.  The TKI only kill at the bottom level, the CMP, as I understand it from my onc nurse.  One thought above that would be, even if the TKI's kill higher up the hierarchy, the actually primitive cml stem cell, it wouldn't matter, because the primitive cml stem cell with the transcript error, (according to the City of Hope article)  has created an environment, to protect her or any future CML stem cells. Therefore CML is much more complicated then thought to be. 

As RCT says we basically have Gleevec or TKI Koolaid.

If the above article were true and the mutations are at the top where the TKI don't reach, then it really doesn't matter which TKI you take except for the side effects, and tolerability of your CBC lab.  This would mean we are far from a cure, and TKI'S are not really stopping mutations, because they may not be killing the primitive stem cell, that causes the mutation.  Perhaps just more speculation and theories.

These are just some of my thoughts after watching the video and reading the articles.   It is something to think about when choosing TKI's???  If this were true I doubt the oncologist or drug companies would want us to understand it to that level, as there is much money to be made from these drugs. Yes we would still need to take the TKI they are keeping us alive true, but perhaps we would be able to take the Gleevec which will become generic, if tolerated, mainly because it would be affordable for many. So much new information to digest and ponder on. Yes?

I would encourage no one to take this as gospel, as no one has said any of these articles or theories are a proven fact, but a theory.  Something to ponder on, when making decision though!!

It is 5am in the morning and I have been reading and searching cyberspace for clues. I am tired.  I may not even be making any sense.  I will read this tomorrow and probably wonder what I was talking about.  Hopefully I did learn some new words and to pronounce them.

PamSouth

[pamsouth]

Hi mbrown,

Here is to that toast.

Glad you were not only able to stay on your current dosage but that you were able to communicate to your onc.

Not sure about your platelets.  

However my diagnoses of CML was in 2005 & I had over 2 million platelets and only about 21 thousand white cells.  The Primitive CML stem cells that started this whole mess, is farther up the chain or genealogy so to speak.  This primitive CML Stem Cells actually effects the whole myeloid side, which would be not only the white cells with the PH+ but the red blood cells and the platelets.  Its in everything. I took hydrea for the platelets for awhile, then Gleevec, all of my cells got low, but the platelets coming down from 2 million never got below the normal range,  Remember the TKI are targeted drugs to kill the PH+ but my platelets and red cells were not normal either as the CML had effected them farther up the chain.

None of this may be pertinent to your platelets. But something to think about.

I pasted Treys the link to Treys article.  I reread it last nite.  There is a wealth of information that would be so beneficial to you.  It took me a couple times of reading it, and meditating on it.  Then there was an article for Lucky that was something to really ponder on as well.  It may take some time to read and digest but I promise you will be glad you did.  Even if you don't understand it all at one time you will get it.  I still don't understand all of it, but believe me I am digesting it and keep coming up with new thoughts.  It is are lives were talking about here.  As my dad always said education, education, education.  I mean its not like we just have a little cold here.

Glad you are feeling happy and are feeling good about your doctor, at least he or she listened to you and is willing to work with you and make you comfortable.

I copied and pasted the articles below, they say it much better then I ever could. 

http://community.lls.org/docs/DOC-1272

http://www.youtube.c...h?v=ce58rAMvKZQ

http://www.cityofhop...and-return.aspx

[Melanie]

Thanks Pam S for all the information and articles! I've read the CML genectics by Trey many times and still trying to get my foggy brain to retain some of the information.   The one on the LST creating it's own micro climate is also very interesting. Makes me wonder when it starts to do that?  Is it response to the TKI drugs hurting it's babies, or does it begin from day one?

If it's from the beginning, maybe that's why we can have CML for years without even knowing it...It's creating it's world to protect itself from being killed. Something to ponder...but it's a beautiful "Spring" day here in AZ, and you know we don't get many of those before it just gets plain "HOT", so I'm headed outside to enjoy the day. Thanks again for your thoughts. I agree that knowledge is very powerful and empowering. Bless this board!  Melaine

[Melanie]

Tedsey, Glad to hear that you are weathering the LBC. Can you tell me how long you were taking the neupogen shots and how often before it was decided to just tough it out? Which TKI were you on and was it full dosage?  I think I'm beginning to believe as your Onc and RCT that the low counts are a condition of the diease and not necessary a side effect of the TKI. Maybe more a reaction of the LSC response to the TKI threatening it's babies. How long since you stopped the neupogen did it take for your counts to start increasing while still on Sprycel? Thanks for sharing.

Blessings, Melanie