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It can be a negative sign - but you will need a trend upward of several log increase to be sure.
Any PCR result < 0.01% is in the noise of the test. Your result can easily be a false "positive". You can continue TFR and monitor monthly as you are doing.
Hopefully the next result will be "undetected" again. TFR attempts can be continued until the loss of MMR (0.1%), but most patients, will restart therapy after 3 months of rising PCR.
K.tam for what it’s worth I too plan to try TFR in the next year or two. And from what I see on this site TFR is a mixed bag and for myself I don’t think I have a great chance for success. But, and this is important, if I fail TFR my hope is that I can at least reduce my dosage. So there are positive options that can still result from your TFR attempt in the event it does not work out.
Scuba,
I started TFR last week after taking nilotinib 150 bid for 1 year and reducing to 150 qd the last two years. Except for one PCR early on at <0.003%, I've been in CMR for those three years.
My onc at Mayo - Rochester, MN will restart me at anything at or above 0.01%. Over the past almost 16 years, I've noticed that Mayo seems to march to the beat of a different drummer. :)
Pat
Hi Pat,
All the best in your TFR attempt!
It does seem many in the research facilities (Mayo, M.D. Anderson, MSK) have their own protocols. 0.01% to 0.1% is typical for restart.
You are an excellent candidate for trying! I assume you will have your PCR tested once a month in the beginning?
Keep us posted.
Hi, Pojo, sorry about that. Scuba thanks for translating - I hate typing so I'll do anything I can to reduce keystrokes! I was diagnosed (dx) in late 2008 and started Gleevec in early 2009. 8 months later I developed TKI-induced hepatitis. I was switched to Sprycel after my liver settled down and was on it for 12 years but I was constantly dealing with pleural effusion the last couple of years even at the low dose of 20mg. I switched to Tasigna in Oct. 2020.
Good luck!
k.Tam, wishing you the best. Your next few PCR tests will likely help determine your possibility of a successful TFR. During the Stop Trials exceeding a BCR-ABL of 0.1% was considered clinical relapse and a TKI restart was in order. If you do happen to exceed 0.1% over your ensuing tests, wait for a confirming test before restarting your TKI and then also see if your doctor will allow you to restart on the lowest dosage of your TKI if a restart is necessary. When you lowered your TKI dosage prior to your TFR attempt, how low did you go and for what length of time were you on this lower dosage prior to your TFR attempt? This will likely help determine your doctor's willingness to restart you on the lower dosage if a restart becomes necessary.
I've been TFR for going on eight years but haven't had an undetected test for almost seven years. So far none of the positive tests have exceeded 0.1% but a number of them have exceeded 0.01%. My last test in October, 2023 came back as 0.01494. Any test of 1.0% (CCyR), or less, presents no risk to the CML patient.
Buzz
Buzzm1 your experience is priceless. I would have never have thought you can go that long without TKI while still having a low level response. This is encouraging news for K.tam.
Buzzm1 I also find it interesting that after 8 years off TKIs you are still posting to this forum. People like you and Scuba contribute greatly to the understanding of our treatment options. Thanks!
Buzz - your experience with TFR where you remain drug free while still testing positive for bcr-abl is very encouraging. It highlights the nature of CML biology and our immune reaction to it. Eradication of all CML cells is not likely or necessary in order for disease control to occur without a TKI.
We all need to remember PCR testing detects the presence of the BCR-ABL fusion gene, which results from a translocation of genetic material between chromosomes 9 and 22 and leads to the production of an abnormal protein that causes uncontrolled cell growth. PCR testing is a molecular test to detect CML at a very low level AND (this is important) is only done on existing CML patients who were diagnosed with full blown CML disease (i.e. bcr-abl/FISH at 100%).
In other words, if random people on the street were tested for CML - a striking percentage of healthy people as high as 30% !! would test positive for bcr-abl (i.e. ~0.01 - 0.1%)! Having a positive test for bcr-abl at this level does not mean one has CML disease. It is indeed encouraging to see your immune system "stopping" CML from advancing without the need for a TKI even though bcr-abl is "detected".
It is theorized that everyone has bcr-abl at some level beyond the limits of technology to measure (i.e. 0.00001% or so). The breakpoint of bcr and abl on chromosome 9 and 22 are so tightly wound together in the nucleus, it is biologically amazing that CML is not more rampant. It is easy for bcr-abl to form when cell division occurs and chromosome 9 and 22 unravel. This is how bcr-abl forms in the first place. And it likely happens all of the time naturally. It's just that when it happens, the body normally recognizes the protein it makes as not normal and limits the cell (apoptosis) population. For some reason, largely unknown, some of us don't stop the process in its tracks when it happens and disease occurs. And, in fact, when disease occurs (white cell count explosion) bcr-abl needs to be over 50% or even highter. This shows you just how powerful the body can maintain a healthy status. Recall when we first started treatment and how quickly we recovered normal blood levels even though CML was only reduced to 70% or 50%. And this only took a few weeks to achieve.
I believe that when TFR is successful, many of us have been able to put the genie back in the box so that our immune system takes back over as before. This is good news. I am so thankful for TKI's as they helped our immune system to regain control and saved our lives.
Hi Scuba,
Your statement that healthy people as high as 30% !! would test positive for bcr-abl (i.e. ~0.01 - 0.1%) if random people on the street were tested is very interesting.
I started Imatinib 400mg on July 2022 with qPCR = 50.2% IS, in November 22 the qPCR was below 0.1 and March 24 undetected. I have been fortunate and my plan is to try TFR as soon as I can, but for now I still live with the concern that if for some reason I don’t have the medication the CML will come back fast, but may be my immune system will be able to control it, during the last years, I increased my vitamin D3 from 26 to 82 now.
Vlacer
Hi Vlacer. Well done on getting to undetectable, and on getting your Vitamin D3 up. I hope you may find this video titled "Reducing or Stopping Treatment Who and When" useful - it is a talk by Prof Clarke from the 2019 patient conference.
https://cmlsupport.org.uk/videos/reducing-or-stopping-treatment-who-and-...
Alastair - Great video summary of CML, treatment and TFR. I particularly liked the inverted pyramid slide from a Rugby ball of CML cells (10^12) to "undetectable" with current technology and still there are million CML cells around.
Blood cells containing bcr-abl are created all of the time because it is easy to do. Translocation errors of this kind are typical in mitosis when genetic material is bound tightly and when unwound for division bits of DNA break off and merge with other bits of DNA. This is what happens to form bcr-abl. Most translocations are benign or are destroyed by the body naturally (oops, that was wrong, next ....). CML disease happens when bcr-abl explodes to Rugby scale.
I firmly believe, the answer to cancer is in our immune system and helping our immune system destroy aberrant cells. This is why anyone trying TFR should also apply nutritional support to their immune system (vitamin D, etc.) to give their TFR attempt the greatest chance of success.
My previous onco once referred to CML as a stupid cancer. His logic being that CML only has one genetic aberration. The acute forms are much more complicated and can involve lots of different genetic mutations and aberrations. We are in a sense fortunate that it’s only BCR/ABL for us. I can see our immune systems fighting this off. Not sure that can be said for other leukemia forms.
Allistair’s video is awesome. I especially like the visual presented that MR4 is similar to less than a grain of sand.
I do want to amend my response to what Scuba said about the immune system fighting off aberrant cells. I did write that I wasn’t sure if the immune system could fight off other more complicated forms of leukemia… But then I remember the success they are having with CarT which essentially weaponizes the immune system to attack the aberrant cells in other forms of leukemia. That I believe helps to bolster the idea that a strong immune system can maintain safe levels of leukemia mutations. We just have to rebuild our immune system to maintain the fight. There is probably a lot more that goes into remaining in TFR that we need to learn but you guys who are doing it really are an inspiration, at least to me. It gives me hope. Thanks!
The solution to cancer lies in genetics of our immune system. Cancer occurrence is an immune system failure.
We like to think of ourselves as 'machines' with parts breaking and in need of repair or can't be fixed even if we try. In reality we are nothing more than chemical reactions.
Truly stunning when you think about it. All life is/are chemical reactions. And that is especially true of DNA which is magical.
Aberrant proteins "coded" by oncogenes, lead to cancer unless other proteins coded by other genes (i.e. P53) shut it down. Science is slowly unraveling the genetic triggers and proteins that if shut down "chemically" can extend our lives.
I don't believe cancer can be "cured" as such. I believe it can be arrested. Our immune systems are the police.