27 replies to this topic

[scuba]

I have been asked in private messages why I feel I can succeed stopping my treatment after only a few months MMR/CMR (i.e. PCRU). There is debate here on this forum and also in the medical research community on what the criteria really needs to be for cessation success with little or no risk. There is also debate on whether complete eradication of Leukemic stem cells is absolutely necessary for cessation success .... or "cure".

 

I believe that eradication of all leukemic stem cells may not be necessary. The scientific community is starting to come around to that idea. Creation of translocation and CML cells probably happens all of the time naturally. But only a subset of us gets full blown CML. The question is why?

 

What I write below is my thinking. No one should attempt what I am doing without full consultation with their doctor (who they trust and is expert in their own right). Most Oncologists will never endorse what I am doing. And for the normal good reasons. My doctor is willing to collaborate with me and oversee this experiment. The risk is mine alone. And since I don't fear CML anymore,  I am willing to try and see if I can speed things up. I am impatient to get rid of CML or more accurately - get rid of taking a TKI. After 5 years, it needs to go away. 

 

My reason for trying and believing I can succeed at stopping is that I am not relying on a TKI alone for CML killing. I have added high dose Curcumin to my diet as an additional nutritional support and also elevated my very low vitamin D status to high normal. Dr. Aggarwal of M.D. Anderson told me that 8 grams of 95% Curcuminoids is the minimum in order to get enough absorption and be therapeutic at getting at these signalling pathways. Curcumin should not be taken by anyone who is on blood thinners. Curcumin is what makes Turmeric root yellow and used in Curry spice cooking. It's been eaten by people for thousands of years.

 

Why should this enable me to now stop Sprycel and continue with just a focussed nutrition approach? It's about the Hedgehog pathway, the Nf-Kb (nuclear factor kappaB)

pathway and the Wnt cell signaling pathways that CML cells need in order to proliferate and dominate our normal blood system. Interfering and downregulating these pathways has been proven to cause CML cells (and other cancer cells by the way) to go into apoptosis, but not normal cells. Below are some research articles from reputable sources () that summarize Curcumin's now known impact on these critical pathways. Is it proven in terms of CML? No. Is it a cure - No. But it seems nothing is ever proven in Cancer research. 

 

Importance of Hedgehog signalling in overcoming drug resistance:

http://www.ncbi.nlm....pubmed/25701353

http://www.ncbi.nlm....les/PMC4325629/

 

Curcumin's impact on Hedgehog signalling:

http://www.nature.co...559a.html#close

 

Importance of Nf-kB signalling:

http://www.ncbi.nlm....pubmed/19378338

 

Curcumin's impact on Nf-Kb signalling:

http://www.ncbi.nlm....pubmed/19723087

 

It is my hope that Curcumin is messing with CML in a big way and buying me time. It is my hope that getting my immune system shaped up (cd4+ & cd8+ cells) by getting vitamin D back to normal it will enable my immune system to do its job. That's the theory anyway.

 

So far I am TKI free. Anemia is going away. And my skin looks great. And no arthritis anymore. So even if my plan doesn't work (and I have to go back on Sprycel) at least I'll look good.

 

I don't recommend my approach to anyone. I am just sharing what I am doing, why I believe it can work and then sharing the results. My motivation is to get rid of the side effects (in my case anemia) brought on by Sprycel and to avoid long term use of a toxic man-made chemical (i.e. Sprycel) that may have long term health consequences in its own right. So far I am in month 3 of no Sprycel and no progression. Cross your fingers.

[pammartin]

Every hour, day, week, month we go without having to take a TKI helps our body for the possibility of having to return to the drugs.  Each of us who are making this choice are choosing our own path and how to walk it.  Our individual reasons are often different, but the goal is the same.

 

I entered into my TKI break thinking it would be a few months at best.  I am now a few days shy of 14 months without having to return.  I have never left the idea I will have to take a TKI again, but I am thankful for every month I do not.

 

Cross your fingers, say a prayer to your God, think positive thoughts, and enjoy life. 

[scuba]

Every hour, day, week, month we go without having to take a TKI helps our body for the possibility of having to return to the drugs.  Each of us who are making this choice are choosing our own path and how to walk it.  Our individual reasons are often different, but the goal is the same.

 

I entered into my TKI break thinking it would be a few months at best.  I am now a few days shy of 14 months without having to return.  I have never left the idea I will have to take a TKI again, but I am thankful for every month I do not.

 

Cross your fingers, say a prayer to your God, think positive thoughts, and enjoy life. 

 

Hi Pam ... it just reconfirms in my mind that the body has mysterious ways of keeping itself 'healed' when it has a little help from its friends. When something gets out of whack and we manage to put it back - it's good to know the correction can stick. I am thrilled that you are at 14 months - no progression. And each day, week, month you go without needing a TKI, increases the odds you never will. But as you imply above - we'll never think we are "cured" - we'll always wonder ... is it happening all over again...

 

No matter - we're TKI free, for now - and maybe forever. Thanks for your reply.

[Gail's]

I know you've just started your stop trial, scuba. At what point did you feel stable enough to go drug free? And same question for you Pam.

[scuba]

I know you've just started your stop trial, scuba. At what point did you feel stable enough to go drug free? And same question for you Pam.

 

That's an intriguing question Gail. When I had two back to back PCRU's (six months), I decided to stop taking Sprycel and then have a PCR taken one month later to see if I was holding steady. Reaching PCRU was a significant event - so I thought if it continues, I'm ready to try.

 

At the one month test - no change. At the two month test - I had a detection, but was told it was a meaningless result and they reported the result as no change. I go for my third month test next week. If it is the same as last test, I continue. If it increases by 1/2 log, I'll probably resume Sprycel. 

 

I was told that in the formal trials on cessation, a patient has to lose MMR before they stop the trial. In my case that would mean I would have to jump more than a log to qualify. They have seen patients rise a log and then go back down. I probably won't let it go that high and instead resume my low dose Sprycel. 

 

Take a look at slide 33 from the report Trey linked:

 

from Trey's post:
"There is a .pdf file available which I cannot link to. But G-search on these terms:

fx mahon cessation blast 8.5

Click on first item "Deciding to continue or discontinue...."

 go to slide 33. It shows the fluctuations that I was told may happen. The rest of this slide deck is interesting reading as well.

[Gail's]

Ok, I'll check it out. How long before you were pcru, scuba?

[SUE]

Michael and Pam,

 

Congratulations on your courage and determination.  You are the pioneers in this fight that we are all waging against cml.

 

Sue

[pammartin]

Gail,

 

My situation was a bit different, I developed severe pulmonary hypertension from Sprycel.   This is a rare condition, Cleveland Clinic has only two cases, myself and one other in all their CML patients.  I was taken off the TKI 3 months before I was diagnosed with the PH.  It was originally pulled because I had fluid around my heart and lungs, the PH was harder to detect because you have to have a right heart cath or echo, and neither was done for a few months because my shortness of breath was blamed on the fluid retention. 

 

I was/am doctor sanctioned to remain off TKI, (I cannot take Sprycel even in a low dose again), until Jan. of this year.  In Jan. my local oncologist gave me ultimatum, either I begin the Bosulif or he was going to release me from his care.  I decided to stay off the TKI, my PH specialist was against both drugs because they are similar in chemical make up and dangerous for me.  My oncologist followed through, he released me and referred me to Cleveland Clinic.  After they ran a PCR test and it was undetectable, the oncologist spoke with my PH doctor and Cleveland's PH department.  All decided as long as I am tested every month and remain undetectable I will be healthier off a TKI.

 

My 'team' have agreed if I show a continued positive PCR I will begin Tasigna, it is the safest drug for my situation.  Until then, I take my PH meds, appreciate how good life can be, and try to forget last year

 

I do not, or would not advise anyone to make the choice I made, even for a month.  It was my decision and it was against my families wishes. 

 

I am simply more afraid of the PH than I am the CML.  I have large blank spots from last year when my oxygen level dropped to dangerous levels from the PH.  I hit a local bank building twice within a few minutes, damaging my car and the building, I do not remember this.  I attended my son's graduation last June and I have no memory except I fell twice going into the building.  I drove miles to oncologist and was taken from the office to the ER and then admitted to ICU.  It was a horrible time.  I had a picc line for 9 weeks and I couldn't handle it, with my poor skin from the leftover TKI in my system I had infections, rejection, and constant sores at the site.  I never want to go to that dark place again.  The CML so far is treatable, and I am thankful for TKIs. I am also thankful I have not had to touch one for over a year.   

 

I am not brave, nor am I forging a way for others.  I am afraid, but right now it is because of the PH. 

[Gail's]

What a tough year for you, Pam. I would be much more afraid of the PH than stopping TKI s. I understand the original oncologists' fear of being involved with your care with your decision to stay off TKI. But glad you ended up where you are now. Seems a much more collaborative group.

[Trey]

I would like to see you succeed, but it is highly unlikely.  Your theories and citations above are not very convincing. 

 

Most of your references do not apply to blood cells, let alone to CML.  Curcumin is basically a natural anti-inflammatory, which although interesting for arthritis has nothing to do with CML.  Dr Aggarwal whom you have cited has written over 500 articles trying to sell the world on the miraculous healing benefits of a plant from his homeland India.  Per your citation, liver cell hedgehog pathways may be inhibited to some degree by curcumin, but blood cells are very different and no such connection has been established.  By the way, hedgehog and Nf-Kb signal pathways are normal human cellular functions, not just found in cancer cells, so inhibiting them may not be advantageous to overall health in the longer term.  But BCR-ABL is not a normal cellular process, only a leukemic one.

 

TKI cessation trials are a good thing for the advancement of the science.  But none of them allow participation by a patient with only a few months in CMR (PCRU).  Most require two years PCRU minimum.  The stats for successful cessation show that the longer the PCRU, the higher the probability for success.  Even when PCRU for more than 2 years, on average only 40-45% succeed, and the definition of "success" is questionable since it assumes the patient can lose PCRU and remain in the studies while MMR.  Of course, MMR means the patient still has between a million and a billion leukemic cells in their body.  This approach of living with possibly a billion leukemic cells continually dividing (does not sound like a cure to me) assumes that this is a reasonable option and that the CML will not turn nasty.  But in fact it has happened.  That is why the clinical trials are important, and several here are rightly involved.

 

My purpose here is not to rain on your one-man parade.  Taking risks beyond what is recommended is entirely up to you.  People are thrilled by seeing someone put their head into the lion's mouth.  I simply want others to understand that what you are telling them is highly speculative and based on a significant amount of conjecture.  Otherwise I would prefer to just sit back and enjoy the show.

[scuba]

I would like to see you succeed, but it is highly unlikely.  Your theories and citations above are not very convincing. 

 

Most of your references do not apply to blood cells, let alone to CML.  Curcumin is basically a natural anti-inflammatory, which although interesting for arthritis has nothing to do with CML.  Dr Aggarwal whom you have cited has written over 500 articles trying to sell the world on the miraculous healing benefits of a plant from his homeland India.  Per your citation, liver cell hedgehog pathways may be inhibited to some degree by curcumin, but blood cells are very different and no such connection has been established.  By the way, hedgehog and Nf-Kb signal pathways are normal human cellular functions, not just found in cancer cells, so inhibiting them may not be advantageous to overall health in the longer term.  But BCR-ABL is not a normal cellular process, only a leukemic one.

 

TKI cessation trials are a good thing for the advancement of the science.  But none of them allow participation by a patient with only a few months in CMR (PCRU).  Most require two years PCRU minimum.  The stats for successful cessation show that the longer the PCRU, the higher the probability for success.  Even when PCRU for more than 2 years, on average only 40-45% succeed, and the definition of "success" is questionable since it assumes the patient can lose PCRU and remain in the studies while MMR.  Of course, MMR means the patient still has between a million and a billion leukemic cells in their body.  This approach of living with possibly a billion leukemic cells continually dividing (does not sound like a cure to me) assumes that this is a reasonable option and that the CML will not turn nasty.  But in fact it has happened.  That is why the clinical trials are important, and several here are rightly involved.

 

My purpose here is not to rain on your one-man parade.  Taking risks beyond what is recommended is entirely up to you.  People are thrilled by seeing someone put their head into the lion's mouth.  I simply want others to understand that what you are telling them is highly speculative and based on a significant amount of conjecture.  Otherwise I would prefer to just sit back and enjoy the show.

 

I understand - I don't agree. The risks I am taking ARE beyond what is recommended. That is my choice of course. The science requires two years until it doesn't. Eggs are bad for you ... until they are not. The sun is bad for you - until it isn't. I just don't buy into the total expertise of the medical establishment completely. To some degree, I do - I am a scientist myself, but not 100%.

 

You have been PCRU for a very long time and certainly qualify to stop Gleevec. But you don't. You have your reasons. You decided to reduce your dose - not because your doctor told you too, you decided. You made your own decision because of your learning and understanding. I have my own learning and understanding.

 

You believe I am putting my "head" into the lions mouth. I don't feel that way at all. CML is a slow disease when in chronic phase. My risk of progression - for all practical purposes - is zero. I am o.k. with the risk. Even Dr. Cortes suggested I can continue another month, he wasn't concerned. Why? He has data that is suggesting that stopping is not as big as risk as they thought. There was a time that they would "stimulate" in order to maintain full dose. Now they are adjusting that back down. Science is not perfect and to think it is is to put faith in people who are not motivated in the same way. This, I very much understand.

 

Regarding Hedgehog pathways - I do very much disagree with you that "inhibiting" them is not advantageous. Research is growing in this area:

 

http://www.ncbi.nlm....les/PMC3643342/

 

Tyrosine Kinase is a normal cell function too! Thats why we have so many side effects, from not tanning normally to worse. And yet we take a Tyrosine Kinase inhibitor so we can live. Your argument doesn't work here. Hedgehog signalling pathway is vital for Leukemic systems. That's why they are exploring Hedgehog inhibition. The good thing about normal cells is they have ways around the inhibition whereas leukemic ones don't - they require mutations. I'm sure you know this.

 

At the end of the day, Trey, if my one man parade works - for me - then I am thrilled. The jury is still out. But I am extremely confident in what I am doing. If the Lion chomps down - so be it. I have a strong neck. And each month is a gift.

 

But just to give you benefit of the doubt - if I don't succeed - I'll agree with you. And I'll be back on Sprycel - low dose taking my Curcumin.

[Marnie]

I was off of TKIs for just over a month due to pleural effusion.  My first PCR after the break was zero.  I was excited.  My next PCR took quite a jump. 

 

My conclusion is that everyone responds differently.  I've been a slow responder since Day 1, which has been a frustration.  It seems obvious to me that I am not one of those lucky people who might have success off of TKIs. 

 

It's apparent that many folks watch your "experiment" and are very hopeful that things go well.  I do, as well.  That said. . .I also hope that everyone will consider their own situation very carefully before making medical decisions.

 

While I'm far more casual about cml than I was at the beginning, I still find it to be very scary.  I have no intention of letting it get out of control.  Zero is a great number.  I hope I get back there soon.  And maintain it for an extended time.  I hope we all do.

[pammartin]

Amen, Marnie, Amen

[scuba]

I was off of TKIs for just over a month due to pleural effusion.  My first PCR after the break was zero.  I was excited.  My next PCR took quite a jump. 

 

My conclusion is that everyone responds differently.  I've been a slow responder since Day 1, which has been a frustration.  It seems obvious to me that I am not one of those lucky people who might have success off of TKIs. 

 

It's apparent that many folks watch your "experiment" and are very hopeful that things go well.  I do, as well.  That said. . .I also hope that everyone will consider their own situation very carefully before making medical decisions.

 

While I'm far more casual about cml than I was at the beginning, I still find it to be very scary.  I have no intention of letting it get out of control.  Zero is a great number.  I hope I get back there soon.  And maintain it for an extended time.  I hope we all do.

 

Marnie, I agree 100%. I am watching carefully for the jump up. If it happens, I'm back on Sprycel. I have no intention of letting it get out of control - that's why the monthly testing is so important. But I am not relying on Sprycel alone. That's the debate Trey and I are having. Under normal circumstances, I would have to be PCRU for two years. But I would never have achieved PCRU on only 20mg Sprycel (M.D. Anderson reported - at best - MMR and barely). Although many of their patients achieved CCyR on only 20mg and that they felt was the critical measure. I was a slow responder until I wasn't. I had difficulties until I started adding additional nutritional support. That really is my main point here. We think the TKI alone will solve the problem - (in the sense of progression free survival, but with side effects felt or unfelt). But perhaps two drugs taking together or as in my case, adding Curcumin, getting vitamin D to normal, etc. can be the trigger to keep CML at bay. That is strictly my view. Trey and others disagree. I respect their thinking.

 

No one should do what I am trying until some day there is a scientific trial that verifies the results. I'll probably know in the coming months to probably a few years. And I do half expect that it won't work. But then the risk is small. I'll try again after a longer time on Sprycel. My main "fear", if I can call it that, is whether my immune system has truly lost the capacity to recognize aberrant CML cells and kill them. That's the key. 

 

But don't tell Trey I tied the lions mouth open with steel wire and a pin. It might not be strong enough. That could hurt.

[JPD]

One thing I wanna know - and this is in the "if it doesnt hurt me, why dont I try it" camp - how much Curcumin should a fella take?

[scuba]

One thing I wanna know - and this is in the "if it doesnt hurt me, why dont I try it" camp - how much Curcumin should a fella take?

 

I think that is Trey's point - that people will try things that others do and not know why. And that is a bona fide concern.

 

Research Curcumin, especially relating to Leukemia as well as other cancers. There is nothing magic about Curcumin any more than vitamin "C" or getting enough fiber in your diet. Sprinkling Turmeric (which is mostly Curcumin) on your salad would go a long way to adding this important spice to your system. 

 

I take a lot of Curcumin. But it can thin the blood and should never be taken with Warfarin or other pharmaceutical blood thinners. I increased my dose gradually to test my response to it (i.e. gastric issues or other effects). 

[JPD]

Im not gonna stop taking my TKIs FFS.  Its a supplement not eye of newt.  I guess Ill just take the amount on the back of the bottle.

[gerry]

Keep an eye out for extra bruising on it.

[pammartin]

JPD, the concern is curcumin is a natural blood thinner.  Because I am already on a blood thinner with the PH meds, I cannot try curcumim.  I bleed like a stuck hog now if I have a small cut, bruise or scrape.  I bruise easier and it stays longer, the last thing I need is a natural blood thinner.  This is why each one of us has to make our own choices and decisions under the advice of our oncologist. 

 

I (sounding like the broken record) always add disclaimers.  And I think they are important.  If you spend any time at all on this board it is easy to realize there is not two people with exactly the same response, symptoms, tolerance just as different are the TKI's taken. 

 

I was too sick last spring to worry about being off the Sprycel, then as I started treatment for the PH and began feeling better I was afraid it would come back.  Most people who develop PH have permanent damage, there are few documented cases where people bounce back to a semblance of normality after diagnosis.  This is why all my team believe it is the Sprycel, because I still have PH but my internal pressures are at a 'high' normal and months ago they were severe. 

 

Check back through the threads, Scuba has noted several times how much curcumin he takes and it works for him.  Disclaimer Alert!  This does not mean it will work for you or you should take the same dose.    I can be a pain in the ass, but I am aware of it.

[scuba]

JPD, the concern is curcumin is a natural blood thinner.  Because I am already on a blood thinner with the PH meds, I cannot try curcumim.  I bleed like a stuck hog now if I have a small cut, bruise or scrape.  I bruise easier and it stays longer, the last thing I need is a natural blood thinner.  This is why each one of us has to make our own choices and decisions under the advice of our oncologist. 

 

I (sounding like the broken record) always add disclaimers.  And I think they are important.  If you spend any time at all on this board it is easy to realize there is not two people with exactly the same response, symptoms, tolerance just as different are the TKI's taken. 

 

I was too sick last spring to worry about being off the Sprycel, then as I started treatment for the PH and began feeling better I was afraid it would come back.  Most people who develop PH have permanent damage, there are few documented cases where people bounce back to a semblance of normality after diagnosis.  This is why all my team believe it is the Sprycel, because I still have PH but my internal pressures are at a 'high' normal and months ago they were severe. 

 

Check back through the threads, Scuba has noted several times how much curcumin he takes and it works for him.  Disclaimer Alert!  This does not mean it will work for you or you should take the same dose.    I can be a pain in the ass, but I am aware of it.

 

Well said Pam ... I am being reminded that I cheerlead too much the path I chose. I've commented on this forum mostly because I wanted to share what's been happening since I started making changes in how I was treating my CML (incorporating my own thinking as well as my doctor's thinking) especially as it relates to Curcumin and other nutrition approaches.  It's been very interesting. People on this forum who have interest should read up on Curcumin and come to their own conclusions. 

 

Curcumin, vitamins, and any other natural substances so far known are not cures for CML. TKI's are not even a cure for CML. It's possible there never will be a cure, as such, for CML. Personally - even if I never have to take another Sprycel tablet again, It will always be lurking in the back of my mind - will it come back? I will always have to be tested for bcr-abl (via PCR). That is the new reality. But I do subscribe to the idea that we can "help" our treatment along with nutrition that supports the immune system in particular so that our TKI is more effective and perhaps even enable a lower dose so side effects are less and yet response maximized. It's a personal journey for each of us. And the good news - one that I am guilty of overplaying - is that CML is very treatable now while in Chronic phase. It's no longer a death sentence. But it is nevertheless a serious disease as any any cancer is serious. We must be vigilant, relentless and ready.