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Starting TFR in November after 9 years of daily drugs

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Hi, my name is Ian and I haven't posted on here for a good few years as treatment has been uneventful, thank goodness!  

My story in a nutshell is cml diagnosed 9 years ago at 65% with 350k white cells in spleen, biggest spleen doctors had ever seen! 2 years on Imatinib 400 lots of side effect but got down to 0.1 but numbers got stuck.  Moved to sprycel 100mg and went down to 0.005 zone quite quickly and have been there for last 7 years.  2 years ago dropped to 50mg sprycel in preparation for TFR trial.  Latest PCR was 0.004 :)

Well today went to Kings and discussed TFR and will be starting in November with monthly PCRs and 3 monthly check ups, with first 6-9 months being critical to holding response.

Wish me luck and hope the immune system can take over, will keep you posted on this thread. Will answer any questions anyone may have also about any part of my journey so far...

BTW This link is a pretty awesome introduction to TFR: http://mypcr.org/wp-content/uploads/2018/09/MyPCR_TFR_FAQ.pdf

Kind regards

Ian

 

That's great, Ian!  Can't wait to continue your story.  So far, that story is exactly the same as mine, except nobody is talking TFR to me.  That's OK.  I'm willing to wait awhile.  Did you never get any pleural effusions on Sprycel in all those 7 years?  I've had four, and each time I took a drug holiday to get rid of the fluid, the CML came roaring back pretty darned quickly, which was discouraging, because I had been having a lot of double zero PCRs (0.005, etc) and thought I was pretty close to undetectable and maybe could stay that way.  No such luck.  Maybe someday.

Hi Kat, good to hear from you :) No plural effusions for me and have tolerated sprycel really well.  I had to push for TFR myself as everything is going well but wanted to try and see, also helping with research at Guys into how the immune system changes when you come off Sprycel.  They will take bloods before I stop and 3, 6 months in and analyse.  Hope it helps other people...

Yes, it will I'm sure - the key to the lock is in the immune system - there's obviously something different about the immune response of someone coming off Sprycel at DMR and zooming back to the left of the decimal point at 11 weeks, and someone who goes for six months (or longer) and never loses MMR.  Thanks for being a guinea pig!

Fabulous news, Ian.  After nine and a half years on Glivec i started TFR at the end of August.  I hope it goes well for you.

Thank you, stopped on Thurs, so far so good just a little achy but that could be because I am getting old!  Also enrolled in a trial at Guys to have my immune system monitored via blood at day 0, 3 months and 6 months to see how the stopping affects the immune system and if they can spot any markers that may help identify others who have these markers  who may stop as at the moment it is 50-50 success.  Could help with predicting success but wont help me...

Keep us posted Ian as some of us hope to start the same journey in 2019.Good luck with holding TFR,

best

Chrissie

Month 1 update, just had PCR result back and 0.001 which is the lowest I have been for a long time, always hovered around 0.003-0.006.  Not sure what to read into it but feels positive!  Had terrible headache and felt like the life had drained out of me for a few days about a week after stopping but feel much more energized now.

Fingers crossed and will report back next month

Ian

Terrific, Ian!  When will they be looking at immune system markers?

Great news, Ian.

0.001% is indistinguishable with PCRU. Any value below 0.01% is meaningless, so you are doing terrific.

But as you pointed out, you have to be watchful these next several months. If your levels stay below 0.01% for six months you are on your way. A blip up does not necessarily mean CML is recurring. You need a trend upwards for that to be the conclusion. Stay the course.

Boost your immune system with vitamin D to give yourself an edge.

Also - when I stopped Sprycel, I had a thyroid attack (thyroiditis) at around two months in. Sprycel affects the Thryoid gland I learned especially during withdrawal.

https://www.hindawi.com/journals/bmri/2013/725410/

https://www.ncbi.nlm.nih.gov/pubmed/20929406

So be on the watch out. Not much you can do during thyroiditis except monitor thyroid function (TSH, T4, T3 and related hormones). I had to take a thyroid hormone for a short time as the attack resolved itself. Avoid excess iodine during your withdrawal period (six months) so as not to overstimulate the thyroid. Your thyroid is fixing itself during your TKI stoppage. I wish somebody told me this before I tested cessation. It was very painful.

Thank you and they will take blood in February for first look at markers after stopping Sprycel.

Thank you Scuba and have been taking spray Vitamin D daily since I stopped as I saw that you had posted the benefits of this to the immune system and other benefits a while back.

Not sure I have been affected by Thyroidism (yet) but do know I feel different and not sure what normal is after 9 years!

Next PCR 18th Dec due to xmas holidays so will report back when I get results and as you say 1st 6 months are key...

 

Month 2 PCR of TFR and result is less than 0.001!! So far so good and counts going down if anything to my lowest ever, not sure I expected that, does this mean the immune system is taking over after 9 years? Maybe daily Vitamin D helping immune system...

Ian - how much vitamin D are you taking? Do you know your current blood level?

Good job Ian.  Really gives us all hope.  All the best to you

Scuba, not sure what my levels are will ask how I can check next time I visit.  Currently taking the following daily as you posted some research and my wife who recommended it based on advice given in her recovery from breast cancer, she is a physio:

https://www.amazon.co.uk/BetterYou-DLux-3000-Vitamin-Spray/dp/B00AWNART4

Ray Sell, think you and hope I can give inspiration to others to stop when ready and safe. I was inspired by the trials they ran and felt like I was a good candidate for TFR, wanted to see what life was like without drugs and save money for NHS, so chased it up for 2 years when finally they agreed...

There is a very helpful FB group only for those in TFR.  You can request to be added. It’s CML Patients in TFR.  Great news about your TFR journey.  And I’m also curious how much Vitamin D?

Update on my TFR so far started Nov 1st 2018:

Month 3 PCR of TFR 0.005 IS

Month 4 PCR of TFR 0.006 IS

So slight rise but still in the boundary that I have been in for last few years.  Am very happy and staying stable!  Been advised not to get concerned unless the reading gets close to 0.1 on 2 consecutive tests and that 8 months TFR is an important milestone without relapse so half way there!

Will keep you posted

Cheers

Ian

 

Terrific news, Ian.  Those of us who are in the "double zero to the right" club are most interested in how you do on TFR, since the current real-life restrictions (in other words, our own personal oncs in clinical practice, not the research bloc) demand a couple of years of "undetected" PCRs before they'll even talk about TFR.  I am hoping your immunity markers will be illuminating.  In the meantime, you've gotten past the initial scary part - yay!  I went from 0.005 to 2.16 in the amount of time you have stayed at 0.001 - 0.005.  There has to be a reason why!

Well the last months results have been a bit of a blow:

0.12 IS 

So now need to get another test done and see if it is a) a mistake, b) a blip or c) an upward trend

Quite a big jump in one month so hoping it is a or b but if c just have to restart the meds knowing I have tried at least...

 

Ian, sorry to hear this - really hope it is a blip. Fingers crossed.

Ian, I sure do know how you feel.  I hope a redo shows differently, but even if not, I know you will recover your former numbers by returning to a TKI.  And that, of course, is what is really important.

I have noticed that it frequently seems that after a long stretch off drug, when people go back on, their numbers absolutely plunge - farther down than they had ever been before.  I don't know what could explain this phenomenon, and I've never read anything about it, but I've definitely experienced it myself and have noted it many times in peoples' stories here.  Anecdotal, but maybe this will be your story, too.  And maybe that means that you can try TFR again someday!

Hi Ian,

Your bump up is unfortunate. It's likely real given it's two logs. Assuming re-test confirms, consider restarting Dasatinib at 20 mg maintenance dose. It will likely drop you right back to <0.01% and you will have less toxicity (less side effects). I maintain my PCRU on 20 mg.

(I do wonder, however, if changing drugs (rotation) to bosutinib or another might eliminate the resistant clone and end CML for you)

@Ian, any news to report?  So sorry to hear about your blip.  My husband went to .12 in month 10 of TFR and then back to .04 and now up to .098.  We are waiting to see his next PCR.  Quite a few people bounce around, but I agree with Scuba that this was a pretty big jump.

This is his 2nd PCR attempt.  After the first one that only lasted 4 months he was back to undetectable very quickly.

Hi no news yet next bloods Monday so will probably find out week or so after that, will let you know on here how it goes but not holding my breath and have some leftover tablets at hand ready to start again...

So PCR is 0.031 this month so down from 0.12 last month so maybe last month was an anomaly, at least will get another 2 months off the drugs and hopefully PCR will stabilise around this level, fingers crossed...

Great news Ian. Onwards!

Wow, what a nice piece of news!  Don't know what to make of such a difference.  Keep us posted on the next one!  What have they learned about the immune system markers, anything?

Yes I was a bit surprised and now a bit confused about what is going on! I wont know about the immune system markers as I just give blood and dont hear anything more unfortunately...  Next bloods on 7th or 8th May so wont know until late May what the next counts will be but will let you know on here.

PCR for April (Month 6 TFR) is 0.067 this month so up from 0.031 last month but still below 0.1 hopefully PCR will stabilise around this level, fingers crossed...

Saw the consultant yesterday and good news bad news.  Seems the 0.12 reading I was sent was actually a typo and should have been 0.012 which is good but that now sets a trend for the CML coming back slowly though the readings are still low. 

Last 3 readings are 0.012, 0.031, 0.067 so upward trend.  Lets see what next couple of months bring but have a feeling that will need to go back on meds unfortunately.

As long as you stay below 0.1 % you can continue TFR.

I am two years into "undetected" and getting ready for TFR. I am using a series of 3 day fasts as an experiment in the hope any Leukemic stem cells I have left are coaxed into dividing and then getting killed by my TKI (my personal theory). Somehow, LSC population has to be reduced significantly in order for TFR to take hold. No one knows how much - just that for 45% of patients who try TFR after two years "undetected" succeed. I'll try anything that stacks the deck in our favor.

If you find your PCR climbing above 0.1% and have to return to taking meds, you might consider a fasting regimen and then try again.

Ian

i can’t believe you had all that anxiety from a typo.  As I mentioned before, my husband really did go to .12 and back down to .04, up to .098 and now bouncing around under .1 in month 14 of TFR.  While it’s a roller coaster we feel every month off meds is a good thing.

Keep us posted and hope your numbers stay low.  

Latest PCR for June is 0.043 down from 0.067 last month so maybe stabilising? Will see next month but gives an extra month off drugs...

Do everything you can to give your immune system all the tools to fight CML without your TKI.

Selenium, for example (cited in other posts) is showing strong evidence targeting CML stem cells.

http://grantome.com/grant/NIH/R01-CA162665-02

https://www.ncbi.nlm.nih.gov/pubmed/24872387

(many thanks to the other members in pointing out selenium! Could it be this simple?)

High normal vitamin D (> 50 ng/ml < 100 ng/ml) activates T-cell attack on cancer cells.

Low sugar (Keto as well as fasting) re-generates immune system and specifically depresses leukemia.

It's possible your PCR will drop to 'undetected' during TFR by you focusing on immune system health. If it does - you have hit a home run. Functionally cured although you will always have to test via PCR. But at least you would be drug free.

Good luck!

@scuba how much selenium is recommended?

@Ian my husband is still bouncing around and last month (month 15) he was at .1 exactly.  Hoping it goes down a bit or at least continues to hover around .1 to stay off meds longer.  Hope yours continues to drop.  

Here is a nice summary of the three types of Selenium all of which participate in cancer suppression:

https://www.lifeextension.com/magazine/2012/ss/selenium-protect-against-...

"In a randomized controlled clinical trial of sodium selenite using 200 mcg per day versus placebo in patients with aggressive head and neck cancers, the supplemented patients showed an increased ability to destroy tumor cells, which is the result of enhanced immune responses.43"

It seems that 200 mcg is the minimum needed to trigger some sort of response. 400 mcg is an upper safe limit.

I currently am enjoying two - four brazil nuts per day - and have been for a couple of years - which - coincidentally corresponds to the start of my "undetected" status. I intend to cut down my brazil nut intake to just one per day and add selenium selenite supplement so I get both organic and inorganic forms of selenium as per the article's notes above.

It's important not to over do it. We are so conditioned on "more is better", but not in this case. Selenium is a metal and in high concentration in the body is toxic (as are most metals in the body). Too low and you don't get any benefit and may even have deficiency. Too high and you get sick. In fighting cancer it seems we have to be on the upper limit of the safe zone in order to be effective. We have to be in the sweet spot of the benefit curve.

What is needed is a solid clinical trial that involves a pharmaceutical grade selenium (so dose is precise) so we know what works.

I will error on the side of keeping my intake below 400 mcg, but higher than 200 mcg. One brazil nut can contain upwards of 95 mcg of inorganic selenium.

Selenium, by the way, is good for so many other things in our bodies including prostate health - but in excessive dose can actually increase prostate cancer risk. Best to have some selenium if you don't already and not add more if you currently enjoy brazil nuts. Go slow with this information.

Thanks, Scuba!  Will pick up some Brazil nuts and seems like it can't hurt for him to chew one a day!

Ali,

Make sure you count out like 1 or 2 weeks worth then freeze your nuts.  The high fat in them cause those to go rancid faster than other nuts.  I buy mine locally in 2 pound bags and they are very fresh.  

Steff

 

 

Steff - Brilliant idea ...

.... Brazil nut freezing that is ... or maybe even refrigerating them.

Started my Brazil Nut regime today to supplement the vitamin d I take.  Hopefully will help immune system and also ease some of the shoulder and hip pain I am getting from TKI withdrawal...

Good general article on Brazil Nuts which are not actually nuts they are seeds! https://draxe.com/brazil-nuts/

 

Ian - How did your TKI withdrawal symptoms occur?

Was it noticeable instantly or did it take weeks and weeks and was gradual.

Felt a million dollars for first couple of months but gradually the pain started getting stronger and movement in my shoulders and hips became harder.  It now hurts doing simple things like putting socks and shoes on and also when driving for long periods, getting out of car for example.  Never had problems previously so assume its TKI withdrawal and onc said it was pretty common an d can subside between 6 months and 2 years...

All the more reason to get off these drugs !

Latest tfr month 8 - 0.031 down from 0.047 and 0.068 the previous 2 months. The trend is stable and hoping the 4 Brazil Nuts a day started taking a month ago and Vit D supplement is helping 👍

great Ian!!!

 

Steff

Great news Ian.

This is the best information I was looking for. Thank you all. Reading this I feel proud, I can soon start my TFR. Hopefully from November or December. Feeling very happy. 

IAN: Hope everything is still going well!

 

Hi Kat:

Question: When you went from .005 to 2.16 what was the time span and were you off of the TKI?

Have your numbers recovered and how long before you were back to the right on the decimal point?

The reason I'm asking is because of what just happened with my latest blood test.

Dr. stopped the  50 mg sprycel for 35 days because of plural effusion/shortness of breath and then restarted Sprycel at 20 MG on June 27th 2019.

I have been taking the 20 MG for 21 days when another blood test was done on July 19th, 2019  and my numbers spiked big time from 0.000 not detected on 50 MG ddaily in May to now at 1.146 July.

Hoping I just need more time for the lower dosage of  20 MG Sprycel  to work in lowering my numbers to the right of the decimal point.

 

Thanks for an insight,

Chuck.

 

 

Chuck, let's see, if I'm reading this right you didn't have a PCR at that 35 days off drug point? So you didn't know what the number was at restart?  It could be that the number you have at 21 days back on is reflective of how far you had slipped in the 35 days off.  Anyway, doesn't matter.  Was the pleural effusion completely gone at 35 days off?  See, mine was not gone (although it had reduced to minimal residual fluid) but because the PCR showed 2.06, I had no choice but to restart.  At any rate, to answer your question:  After restarting at 50 mg, the 2.06 had returned to .61 after 3 weeks; I then reduced to 25 mg (splitting the 50's) and after 5 more weeks it was .02.  After 5 more weeks (that's 10 weeks at 25 mg, 13 weeks total back on any drug) it was returned to 0.005.   For additional info, on a prior stop/restart: I was at <.01 when I had to stop for a pleural effuson and after 9 weeks off Sprycel it had risen to .47 so we restarted (at 50 mg) and after 6 weeks it was .05 and after 11 weeks (total) it was again <.01.

My thoughts are that POSSIBLY restarting at 20 mg was too low - Scuba will dispute - we simply don't know on this.  My doc felt 50 was safer - research will tell us for SURE one of these days.  Other thought is - your 1.something PCR was a mistake.  Keep us posted.

Ian:  Let's start calling your .0whatever the "new normal" LOL.

I'm replying here as my husband's PCR in month 16 of TFR was up to .18 last month.  @kat73 you really went all the way up to 2.06 and got back down to MMR very quickly as you described?  And I've been worried if he goes up any higher. than .18.  There are a couple of people on the TFR FB forum that have been around .18 to .2 for several months and haven't returned to meds.  One of them just went back down to .06 today!  But I hadn't heard of getting as high as 2.06.

At this point my husband will stay off meds if his BCR/ABL is stable or goes down from .18.  I'm watching Ian's journey here and on FB and hoping his remains below .1.

Both my husband and I are eating brazil nuts and taking Vitamin D!

(Just as a refresher, this is his 2nd TFR attempt.  It was actually TFR by default after taking a drug holiday after severe shortness of breath on 50 mg Sprycel without PE.  When his PCR stayed low he just stayed off meds.   It took him 10 months off Sprycel to get rid of the SOB.  While going back on 20 mg Sprycel is an option, he prefers to go on Bosulif if/when he has to return to meds.  He will start at 100 mg and titrate up hoping that 200 mg will be enough to get him back to MMR with few side effects.)

Yes, Alison, it was 2.06.  Of course, it could have been a mistake, but my onc certainly proceeded on its being accurate.  Although dismayed, I wasn't worried that I would get back down quickly, as I had before and people generally do.  But I sure would like to know what's "missing" in my immune make-up or whatever it is that makes me zoom so fast upward when off drug.  I don't think I'm ever going to be in the TFR cohort.  Oh well, not complaining.

@kat73 I think that’s the gazillion dollar question: what makes some people part of the 50% that seem to have TFR success?  My husband is happy for the drug holiday as long as it lasts since he knows he’ll be back on meds. 

It's my theory Kat, that rapid re-start of CML following cessation suggests a large pool of leukemic stem cells (LSC) continue to remain in the bone marrow.

This population has to get reduced so that over time, LSC's are just too few in number to re-initiate disease in the absence of a TKI. Also - LSC's, when dividing, are susceptible to TKI's (which is probably how they get reduced over time). Coaxing LSC's to divide, I believe, is key to their eradication (to low enough level to not matter).

What causes LSC's (or normal HSC's for that matter) to divide? The body produces cytokines (proteins) telling the bone marrow - quick, we need more blood cells. This signal causes LSC's to come out of quiescence and divide in larger numbers than what would otherwise occur. What causes the body to produce this blood making stimulation?

1. massive blood loss (trauma).

2. Disease (such as fever inducing flu, bacterial infection, etc.)

3. Fasting (for more than 3 days at a time) and subsequent re-feeding (which is the trigger to build blood).

And there is evidence that Misoprostol as well as selenium may interfere with LSC's as well.

Worth looking into .... However, I would avoid deliberately pursuing number 1 and 2 above.

Agreed, Scuba, that there is logic and promise in the proposition and those methods.  But what about all the successful TFRers who never fasted or took selenium or mistropopal (sp) or got friendly with leeches?  I know there's some research into NK differences in immune systems (something I hope we learn from Ian's case someday) and I think there just have to be some markers, some sort of profile that will sort this out.  Then maybe there might be something to be done about it.  But, yeah, I'm plodding along using the exhaustion theory.  If research ever PROVES selenium and/or misto-whatever boots those lazy LSC's outdoors where they can get gunned down by the TKIs, I'll happily take them.

On the ~50% who were able to stop without doing anything special .... lucky.

They probably had a relatively low LSC population to begin with and/or when they started treatment their LSC's were dividing into oblivion due to TKI attack. I believe the "odds" one patient has an LSC population that is dormant (quiescent) vs another patient  whose LSC's are active is a coin flip.

Quiescent LSC's escape destruction by a TKI and dividing ones do not.

So my goal remains to bias my biology so that LSC's are dividing (via fasting) as well as taking selenium and curcumin to attack them in other ways. Stack the deck in my favor sort of speak.

Didn’t mean to hijack Ian’s thread, but happy to report my husband’s 16 month TFR PCR down from .18 to .111.  @Scuba  Added a third Brazil nut daily .   That means at least one more month off meds and hopefully more. Yay.  

Good to read on 16 months TFR!

This selenium idea has me very intrigued. I alternate between brazil nuts (two - four a day) and a 200mcg supplement. I never take both at the same time, but figure alternating between organic and  inorganic form may help.

I will try TFR beginning perhaps this September! We'll see.

Latest results are very encouraging down to 0.017 from 0.031 last month and 0.043 and 0.067 months previous.

Saw CML Specialist in Kings last week and he said all is going very well and the pattern he is seeing is becoming more common, as in stop drugs, counts rise slowly then the body takes over and they start dropping and he even said I may get to undetectable!!  I am still nervous but at month 9 now and he said the high risk stage has gone but there are still chances of relapse, but very pleased with progress!

So onwards with Vitamin D supplement and 4 Brazil Nuts a day and keep seeing what the results bring... He also said after 12 months may go to 2 monthly checking.

So happy for you, Ian!  As far as I know, you are the only person I can think of here who has stopped TKI's successfully without being declared undetectable first.  I know that two zeros to the right of the decimal is considered commensurate with undetectable, but my onc is NEVER going to let me try TFR unless and until the labs come back 0.0000.  Plus, I have a bad history of the CML zooming back super fast after stopping Sprycel for pleural effusions.  Next time I see the onc I'm going to mention your case and what your specialist said about the immune system's effects with the rise and then subsquent dip.  Is he going to present his data at some point, do you know?

Latest result from August 0.030 so little rise from 0.017 but still below 0.1 so TFR 9 months so far and at least another 2 months!

Hi Ian

I'm pretty much in the same place, having stopped taking imatinib in late October 18.

March 19     0.03%

May 19        0.012%

Jul 19          0.02%

Had a test a few weeks ago - consultant will call me if there is  problem, which he would have done by now. Next test early November.

 

You are in the noise of the test. You are looking very stable.

Also - we don't know if your levels are now the result of normal bcr-abl formation that happens naturally in normal population. In other words, if we randomly selected people off the street and tested them, upwards of 30% would show your numbers and they do not develop CML.

According to Dr. Cortes, he believes it takes 5 - 7 years for CML stem cells to burn out once 'undetected' has been achieved with TKI's. At 2 years ("undetected"), your body is able to fight off the now depleted state on its own without drugs. It's cross your fingers time, but looking good.

Results today not so good up to 0.084 from 0.030 last month but still below 0.1 so have couple of months drug free at least ahead. 11 months TFR now, so will make it over a year drug free but still jumping around!

Ian - There does seem to be a trend, but it is still below the "resume" threshold.

Are you taking selenium? (200 mcg per day). Recent research suggests selenium interferes with leukemic stem cells. Anything you can do to augment your immune system to keep a lid on CML naturally may help (including vitamin D). The idea is to see a trend downward again by next test.

Yes am taking 4 Brazil nuts daily and also supplementing vitamin d. Hopefully just bouncing and next month will be a key result 🤞