My oncologist called me yesterday and said they had found a donor match for a stem cell transplant and did I want to proceed?
So a little of my story, I have been on IBRUTINUB for two years and am currently feel great as my lymphocyte count is 16.5 and neutrophils at 3.8.
He said because of my higher risk genetic mutation (I am 17p deletion) that it would be advisable to do a SCT when I am in a strong healthy state.
In the past three months I have done two - three day fasts and saw my lymphocyte count go down to 17.1 and then 16.5 where it stands currently.
I am not certain if this drop was aided in my fasting – but I feel it has aided .
At this point, I feel like proceeding with the SCT would feel like ‘throwing in the towel’ and when the specialist is telling me there is only a 50% chance of surviving a SCT – the odds are not good – so why do it?
By the way, my answer to my oncologist was a ‘no for now’.
Have any of you been faced with this type of decision? I appreciate your feedback.
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steve_canada
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There is one statement that I suspect you have misinterpreted.
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The survival rate for SCTs is usually 90% not 50%, but the success / cure rate is in the 30% to 50% range. So you may want to clarify that with your doctor.
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Also, many CLL patients with 17p formerly had very short life expectancy when Chemo was the only option.
But with the new targeted treatments in use since 2014, the life expectancy is dramatically improved. So most 17p patients are going through multiple sequential treatments with drugs like Ibrutinib/Imbruvica, Venetoclax/Venclexta, and Idelalisib/Zydelig before considering a SCT.
Hi Canuck, A SCT uses stem cells from a donor (different person matched as closely to your genetics) and attempts to replace your entire immune system. As mentioned about 10% of patients do not survive, 30% succeed and get a different immune system with no problems, 30% have GVHD (Graft vs. Host Disease) where the new immune system attacks parts of the body, and 30% have the old original immune system wipe out the transplanted cells.
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In CAR-T therapy - a group of T cells are removed from the patient's own blood and altered in a laboratory, then grown / expanded / mutiply to become hunter killers specifically targeting the CLL cancer cells, and re-infused into the patient.
For many other Leukemias & NHLs this process is very successful, but so far, the success rate in CLL is around 30%. While the first month after infusion can have some serious medical issues, the survival rate is much better and the issues like GVHD are far less than SCT transplants.
Where are u located In Canada to get an SCT? Who’s your Oncologist if you don’t mine me asking ?
I would seriously consider it , you have a. Chance to Most likely get off of all medications and taking a forever pill. Stem cell has a much higher % of curative than Ibrutnib
Steve there is a lady on here from Australia , Debbie in OZ , she recently just had a stem cell transplant a month or 2 ago ? . Maybe you can read about her experience ?
Deb's CLL was aggressive, she is young (in her 40s now) with a young family and FCR, then Venetoclax failed. When she was diagnosed and her CLL turned out to be aggressive, she was told by her specialist that a bone marrow stem cell transplant was on the cards. Thankfully CAR-T therapy has come along way since Deb was diagnosed. So I don't think Deb's experience is all that relevant to Steve.
The risk associated with bone marrow stem cell transplants increases with age, so they are less and less used as you get older, with the need for them thankfully reducing due to the much better treatments now available. Steve, you have more options now than Deb had, should Ibrutinib eventually stop working for you, with more likely to come. Read my post about all the BTK inhibitors coming on the market (a non-covalent BTKi could work for you if you develop resistance to Ibrutinib). Then there are all the BCL-2, PI3-K, anti-CD20 and now ROR-1 drugs I note in a reply to that post, before a transplant or CAR-T treatment would be in consideration, I suspect. healthunlocked.com/cllsuppo...
At least your specialist is looking at all options for you!
Interesting read. Looks like Dr. Gorski has his own biases though. The patients with no progression perhaps stuck better to the keto diet because they had a less aggressive disease? That's a funny conclusion. Seyfried will preach to whoever is willing to listen but it does not reduce his credibility. The most important question is how to exploit cancer's metabolic derangement to fight it and Gorski has no answer. Yes, it's complicated and is both a genetic and metabolic disease. But other than cut it, burn it, radiate it poison it, there's nearly no other option. Exception is the new blood cancer therapies. So we are still stuck and have no real progress. Trying to depict keto as something very hard to do and thus not a solution because people can't adhere to it does him disservice. Some people would rather die than stick to keto and that's OK. That's their choice. In combination with fasting and conventional therapy keto needs to be tested for improving outcomes. But nobody seems interested.
Don't we all have biases? That's why properly designed clinical trials are so very important.I note that in your report about your lymphocyte counts you state "I was hoping for the fasting/keto combo to reduce ALC levels but that did not happen", but without a statistically meaningful large enough number of people trying, including a placebo group, we won't know whether anyone is likely to benefit or be worse off from a given intervention.
That's true. Most everybody has a bias. But I don't think I have 😊 any. I just cut known offenders from the diet and eat the rest. I wish somebody ran a RCT on keto/fasting on many different diseases so we'd have definite answers.
From birth we are conditioned to be biased. It takes daily effort to resist it, and much more to seek and observe credible evidences that provide accurate measure.
You used the term "cure" which is not uMRD. I wish it were! I've been uMRD off and on with Ibr...its just the detection in 1/10000 not sensitive enough.
Here is an article you might find helpful. Be aware that stats can be misleading/confusing as already seen with the misunderstanding about survival rates.
Like you, I would lean strongly to not having a stem cell transplant. But there is more info I would want to consider.
I think the survival rate and success rate is much greater for younger people with a lower disease burden. Since stem transplant can be a treatment of last resort for seriously ill folks, the statistics might be very skewed and not applicable to you.
I suspect your doctor might think that statistically with existing treatments, eventually you will relapse and after exhaustion of novel agents, need a stem transplant anyway, but you may end up choosing it at an age and health situation where it is less likely to work.
So I would want to know that stats not for people overall, but rather for people your age in otherwise good health. I bet that is very different than the overall stats with a much higher survival rate.
The other side of the coin is that we all might have better options five and ten years from now. CarT treatments for cll might improve greatly. Other drugs might be developed in the next ten years for cll that make transplants obsolete for cll.
I dont think I would choose the transplant either, but I would keep an open mind if my doctor suggested it. The survival rate and cure rate Len quoted for you is probably for the overall population, not for someone young and fit and with lesser disease burden like you.
Yes he is a specialist but he is thinking that if IBRUTINIB stops working for me , his plan is to transition to 2nd line of targeted therapy which in Canada is Venetoclax and Rituximab.
And if that doesn’t work he would rather have me strong going into a potential SCT.
But honestly, deep down in my heart , I’m not doing it. I would rather consider alternative therapies if all else fails.
Currently looking at oral DCA/AVEMAR combo, Exogenous Ketones, Intermittent Fasting , Meditation
Steve- i am 17p and tp53. and was diagnosed almost at same time as you. However without knowing your age and what kind of sct your doctor is suggesting RIC=reduced intensity transplant was in that article-i cannot give you an opinion.
Will it be ric or regular? dana farber has reduced intensity and outpatient kinds of transplants. I am 70 and if i have one it will be RIC and hopefully out patient, The original full transplants are the ones that lay you up. the difference is full replacement of all blood versus just getting a small amount of donors cells to jump start your immune system. you need to know just what you are getting they are all allogeniec
It is most likely a RIC, from my understanding CLL is always treated with RIC regimen. The full "knock out the entire bone marrow" chemo is still used for other very aggressive types of leukaemia. With RIC you would be likely to spend some time in hospital, but you are not likely to have to do full isolation.I have done a RIC, after R-EPOCH dose adjusted (can read details in my profile), the RIC was milder to go trough than the heavy R-EPOCH treatment, but the side effects, like fatigue etc. took longer to normalise regain from after the chemo from HSCT.
My view is that if IBR stops working THEN try the next drug and if that fails THEN consider it and be ready. If Ibr is working you will be still strong if it stops working. I would say buy time. However, these decisions are difficult. I tend to go with my gut if it feels right or not.
Leo I’m not gonna jump into this - not with all of the new targeted therapies on the horizon .Also , I have always been interested in supportive natural therapies - maybe that’s the Cowboy in me....lol
Hi. I have primary MF, aged 56 at the moment. I am very well maintained on 30 mg of Ruxolitinib daily and have just finished discussions with the transplant team about me possibly undergoing a stem cell transplant. They said because of my young age and well maintained condition, I was a good candidate.After a lot of soul searching and sleepless nights, I told the transplant team I do not want to go ahead at this time.
I decided I want to spend as much quality time with my husband while I am able to before entering a long course of intensive treatment that only has a 50% chance of success like you.
I think we have gone with our gut feelings and have done what is right for us.
Yeah you trust your own gut feelings ... well said . I mean once you do it - they effectively wipe out the garden and plant new seeds.
I’ll agree it sounded ideal to me initially but it definitely is not the silver bullet it could be - at least not for me.
Having said that - a dear friend had multiple myeloma and nothing worked for her so she did the SCT out of last resorts and happy to say she is back to work and doing well.
Why mess with what is working? I am high risk cll too. One oncologist wanted carT transplant. Got 3 more opinions. They said no. I can't verify, but they said 5 trials were done on high risk cll. All 5 died. So they stopped these transplants. I've been on ibutrinib for 4 years and feel great. May God lead you to the right decision.
No plan. They mentioned other targeted therapy available.
Hi Steve we have spoken before. I am also from Toronto. I am meeting with the transplant team next week. Ibrutinib stopped working for me this year. I am planning to proceed with the allogenic stem cell and we have found a donor. I have an aggressive form of cll and I have decided that the transplant is the best route for me while I am still young (50).
God bless you with a successful surgery and quick recovery. Sandra
I did chemo the first time and ibrutinib when i relapsed. A friend of mine did the stem cell transplant with dr Lipton 12 years ago. He’s still doing well. Yes I am also going to Princess Margaret
I’m actually an “email” friend with him. If you want to talk to him directly let me know. He’s an amazing resource because he has been through the whole process.
Hi Steve. It isn't much to offer, but I recall reading on my own charts (from Alberta) that the "cut-off age" for transplant is 60. This may be why your doctor is considering a transplant at this time. I would recommend a second opinion regardless.😊
Hi steve_canada, - I just found an on demand video discussion from this year's ERIC conference October 3, in Europe where 7 CLL experts from around the world discuss the exact question you raised. This for medical professionals so some of the discussion is in MedSpeak but it is mostly understandable with a few Google look ups of terminology.
When I was diagnosed in 2011, with my complex karyotype including unmutated del 17p & 11q, a stem cell transplant was recommended. The problem with all the "success/failure" statistics in my opinion, is there is very little data showing 1) whether or not a certain patient population has trouble regaining marrow function to where they are now dealing with ongoing inability to make RBC's, or platelets, or neutrophils, etc. etc. and 2) how long after the transplant total marrow recovery occurs, if ever. My grandmother was "cured" of cancer but died of an infection 6 months after treatment was finished. Her death was not included in cancer mortality statistics. Treatment throughout the years has changed my FISH to now I am only 17p/TP53 del & 13q.....the 11q and a few other minor deletions are gone. And you also have to consider the percentage of cells affected...lower percentages can have a different disease course than a higher percentage of affected cells. My FISH from May states that 17p del has the poorest outcome/lack of response to therapy, especially if involving at least 20% of cells (my italics, not the reports). Before Venetoclax & some of the newer agents, I too was disappointed at the potential of having to take forever after something like ibrutinib. I wish I could do another SC Campath treatment, I was in remission for about 5 years. But the docs say its "too toxic".....as if a stem cell transplant doesn't have at least as much marrow suppression/risk of infection! I personally will not do CAR-T or stem cell transplant unless it absolutely was the very last option available, until and unless the widespread marrow suppression is dealt with somehow. New treatments are in the pipeline, and most likely will be for some time to come, as CLL becomes even more widespread.
This is a highly personal decision that you have to discuss with your docs, after educating yourself to all the pros & cons. This site is great for asking questions & getting opinions, I definitely feel less "stressed" and/or "isolated" sharing in this community.
Hi Steve,I too am 17p deleted, and although Ibrutinib worked great for me (I was on it for only 3 months), I chose to go for allo-SCT at Princess Margaret in May 2019.
I struggled with the decision too, and even now I cannot be sure if opting for transplant was better/safer than staying with BTK inhibitors.
My situation was as follows:
1. Post my diagnosis in 2014, I steadily lost energy till 2018, although I was not on any medication. I did include green tea and turmeric, as well as vit C & D to my diet and I was gung ho about alternative medication and diet for controlling my CLL. My WBC stayed around 13-16 though my RBC and platelets slowly but steadily declined. I also struggled with sinusitis and chest congestions that lingered.
2. In Nov 2018, I landed up with Richter's transformation. 17p del patients have about 44% chance of RT vs. 'normal' CLL (1.5%).
3. Chemo (RCHOP) failed by 2nd round. I was on Ibritinib, and Venetoclax was the second resort.
4. I responded extremely well to Ibrutinib, and started to regain weight and stamina. My WBC counts shot up (Ibrutinib starts to draw out the CLL cells from the marrow and lymph glands) and then started to drop till it was back around 13-15. My immunity was shot though, and I was put on IVIG.
5. My CLL specialist at Sunnybrook (Dr. Spaner) recommended me to go for SCT, and was very skeptical about BTK inhibitors working beyond a few years. He confirmed the recommendation with his colleagues at MD Anderson and Mayo Clinic. He also was not in favor of Car-T vis-a-vis SCT. As far as I know, CAR-T is attempted after SCT fails (based on Brian Koffman's case, and 2 other people on this list). Dr. Spaner also stated that progression in high risk cases, once BTK inhibitors fail, is real rapid. I can attest that the onset of RT and the resultant weight loss and fatigue is in days and weeks. I lost 25% of my body weight in just 6 weeks and I could barely walk 10 steps when I was admitted!
6. The transplant team at Princess Margaret (Dr. Lipton is the head of the team but they all work together as a team and discuss all patients in their weekly meetings) basically echoed the same (though one of the understudy specialist did tell me in private that if a donor is readily available, then it might make sense to delay the transplant).
7. My understanding is that BTK inhibitors generally tend to stop working over time (there always are exceptions), and even if they get you to MRD undetectable status, they only keep you in remission. Furthermore, your immunity takes a hit and never quite recovers. That means, you need to take the BTK inhibitors for prolonged periods of time, as well as IVIG infusions. The current policy in Ontario is that Ibrutinib can be prescribed (and covered) for prolonged period of time, but Ventoclax is prescribed and covered for only 2 years. I do not know if it is automatically renewed. IVIG also is also quite expensive and has many criterion for renewal. I think I read on this list sometime back that IVIG might be prescribed on a case by case basis, only if you consistently fall sick or get recurrent infections.
8. The above thoughts made me think that staying on BTKs meant a low risk option but with protracted battle of constantly dealing with side effects and failing immunity, while SCT was a high risk option but with the potential for cure. I was told that the transplant has a 30% success rate for 'full cure', and another 30% success rate of cancer cure but with chronic GVHD issues (trading one disease for another). So about a 60% success rate and about 7% chance of graft failure and about 30% chance of cancer recurrence. CLL has the highest probability of cancer recurrence.
9. Car-T is the newest kid on the block, and in Dr. Koffman's case, has kept his CLL under check after his stem cell transplant failed. He recently has gone off Ibrutinib too and still is MRD undetected. I do not know about his immunity issues, but what I understand is that Car-T does not help you regrow immunity.
So I will agree that it is not an easy choice. I know someone who is dealing with chronic GVHD issues and that is as bad for quality of life as is failing immunity.
Stem cell transplant can be successfully deferred - as long as you are in relatively good health and a donor is readily available.
Stem cell transplant is also most effective if you have the CLL under control (ideally at MRD!) and you are young and good health.
BTK inhibitors are great and the side effects are way easier to deal with than chemo's side effects - but there are no guarantee about how long they will work. And you will always remain immune compromised.
RT was a terrifying experience - the rapid weight loss and the suddenness of debilitating fatigue within weeks, was something that I never want to experience again.
The recovery post SCT was also nerve wracking, especially the first 6-8 months as the risk on infection is the highest at that time. However, with the present covid situation, it kind of feels manageable. As one of my friends commented - I was quarantined and in isolation from May 2019 onwards, and the rest of the world followed suit in March 2020.
So I went for the high risk option. I managed to avoid any infections, and have had no GVDH issues so far. My immunity is re-growing (IgA, IgM & IgG levels), and my stamina and energy levels are nearly back to pre-diagnosis level.
But the story could easily have been different. There is someone I know (and I think you know him too), who underwent SCT after Ibrutinib and Venetoclax failed. After 18 months, he landed up with GvDH and now his cancer has come back.
I just had a quick read of the link provided by avzuclav, and it states something that you should discuss with your oncologist (CLL specialist) and Dr. Lipton, as it sounds to be opposite of what is commonly understood. I have copied the part:
Prior NAs do not appear to impact the safety of alloHCT, and survival outcomes are similar regardless of number of NAs received, prior chemoimmunotherapy exposure, or NA immediately preceding alloHCT.
This study had only 65 patients, and all had prior exposure to NA (BTK inhibitors) and some to chemo and none had RT, and they compared these results to the standard outcome of SCT (where everyone had prior exposure to chemo) and found similar outcomes.
I haven't fully digested the findings, but my first thoughts are that the smallish sample size implies that the results cannot be generalized. But it certainly is a question worth asking Dr. Lipton.
What I was told by Dr. Spaner and the transplant team at PMH was that prolonged exposure to chemo (they included BTKs in the chemo list) reduces the efficacy of SCT, and obviously low disease load has better outcome than high disease load.
My marrow was 98% infiltrated with CLL at diagnosis of RT, 80% after 3 months on Ibrutinib, 60% at 3 months post transplant, 10% at 6 months post transplant, and 'a few cell' at the 9 months mark. I was so annoyed at the 'few cells' remark by the pathologist that I refused the 1 year bone marrow biopsy unless they were willing to provide me either a percentage value or a MRD status. Apparently, it is the pathologist's call and the transplant team or the patient do not have a say!
In case there is no downside to delaying SCT, then it might be worth staying on BTKs for as long as possible.
But if prolonged exposure to BTK reduces the efficacy of SCT, and if transplant under rapidly progressing CLL, or worse, RT, has a suboptimal outcome, then the choice might be seen as risking death/GVHD for 'cure', or staying with BTKs and deteriorating immunity and quality of life.
Good luck with your choice!
Feel free to directly message me if you want to know anything more about the process...
Thank you for sharing your experiences and the factors behind your decision for Steve and others in this situation, who will greatly benefit from what you've shared. I'd just like to clarify a few points that you've raised:-
Per your point 7, "My understanding is that BTK inhibitors generally tend to stop working over time (there always are exceptions), and even if they get you to MRD undetectable status, they only keep you in remission." The following paper showed that per Figure 1, after 5 years, 70% on were still maintaining control of their CLL with Ibrutinib.
Long-term efficacy and safety of first-line ibrutinib treatment for patients with CLL/SLL: 5 years of follow-up from the phase 3 RESONATE-2 study
Of the around 30% who stopped taking Ibrutinib, most developed resistance, but the second paper notes that the trial included patients on their second or later treatment, where the risk of developing resistance is higher. Not being able to tolerate the side effects is also a worrying reason behind patients ceasing, but thankfully we have Acalabrutinib and other second generation BTK inhibitors with lower side effect profiles becoming available.
With respect to "Furthermore, your immunity takes a hit and never quite recovers." While it is true that maintenance therapy will continue to eliminate healthy B-cells, impacting our ability to make antibodies, T-cell immunity has been shown to improve per this paper:
Ibrutinib treatment improves T cell number and function in CLL patients
Results: Ibrutinib markedly increased CD4+ and CD8+ T cell numbers in CLL patients.
Hopefully limited term combination therapies will enable recovery of our ability to make antibodies and a few members have reported this - including one member on Ibrutinib monotherapy - their second (non-chemo) treatment.
As you note, CAR-T therapy has the same impact in eliminating healthy B-cells - well until switching off the CAR-T cells is mastered. That's why Dr Koffman is on regular IVIG therapy, where as you note, approval is dependant on experiencing both low IgG counts and having had serious infections.
As I've noted before, restoring our immunity post treatment is a major remaining goal in totally restoring our health after a CLL diagnosis. Bone marrow transplants avoid that by hopefully replacing your bone marrow stem cells with the donor's fully functional stem cells, but with specific risks that you've noted. While treatment advances are providing us with way more choices, we unfortunately will have to wait for the long term data to know with greater assurance of our best path, which will still be specific for each person.
I fully agree with you Neil, and thank you for the links!Like I said, my 3 months experience with Ibrutinib was excellent, and I still am not certain if the decision is clear-cut or even if I made the right decision.
I tried to highlight my thinking process, and the pros and cons as I understood them, esp. as a 17p del case of CLL.
Hi Steve This is a timely post with lots of good information sharing for me to absorb.
Especially as I also live in Canada (Toronto)
I am tp53 mutated so high risk as well
Currently on Ibrutinib first line since Aug 2018.
ALC has gone down to and hovered around 8-9 since July2021
With a lot of unusual sensations all over my neck (burning and aching) worse on left side and some puffing on my left clavicle I am being to suspect Ibrutinib resistance is beginning.
Meeting with my Doctor in Hamilton mid Dec to check this out with him
Something similar happened in March of this year with a little less severity and went away for a while so I’m hoping it might go away again.
If not - I need to be looking at my options and to be honest I feel considerable distress at the prospects of making the wrong decision.
I think in the back of my mind I have been wanting to hang on as long as I can until CarT is available and has become a safer option
Considering how individualized & complex everyones CLL disease is and how it affects other body systems differently in different people, I don't think there's a "wrong decision" to make regarding your treatment.....please try not to stress about it! There are Pros and Cons to every treatment option, plus your personal life/how you are living it and how each Pro or Con affects your particular situation. Spend some time educating yourself about your options if you haven't already done so recently & Do the best you can; whatever you decide will be "right" for you at that moment in time!
Thank you Steve for starting this post as this subject has been weighing heavily for me. I have read everyone’s response I’m yet to read the attached medical papers but one question I do have for members here that might know, I had followed Deb in Australia’s Car T cell journey and she mentioned something like you can have Car T before Stem cell transplant (Allogenic) but not the other way around, this may have been an individual issue for her, I’m not sure, I’m just very unsure of going ahead with Stem cell Transplant also. I’ve got two Haematologists highly recommending I go ahead, and another who is looking after me whilst on a clinical trial with Loxo 305 and Venetoclax saying that I could get years out of my current treatment. So confused as there are differing opinions. I am 49 (Tp53) have had FCR, Ibrutinib, now on current clinical trial.
Hi Billarina, there’s probably a lot of us in the same boat where we are worried about making the wrong decision .
But with so many new targeted therapies on the horizon I’m hoping that something new comes up.
I like many of you have had too many sleepless nights worrying about making the wrong decision and now I’m saying out loud ....I won’t be doing a stem cell transplant.
Most current CAR T trials have excluded patients that had an allogenic transplant from taking part, this might be the reason she stated she could only have CAR T before transplant.
I am likely to head towards a second Allogenic HSCT. I was first diagnosed with CLL del17p, and then had a Richters Transformation.
Richters Transformation (RT) is terrifying, absolutely truly terrifying. The times of disease progression with RT are the only times in my life I have really been afraid and truly terrified for my life. To see your lymph nodes from neck to groin grow from nothing to 2-3cm in two days when the treatment is not working is something I do not wish for anyone to experience.
The prospect of being cured not just disease under control does also have important value. Before the Richters relapse, four months after HSCT, the prospect of actually being cured was a great relief and very valuable in regaining a sense of normal life. Even with the CLL under control I find it will remain in the back of the mind. Especially with del17p that is known to mutate and transform.
I am not sure what the percentage of transformation is with del17p, but if they are as high as in the range of 40% as stated above I would be inclined to go for a transplant sooner rather than later. Not as the first option, but I would not wait until I was on the last available novel agent.
The procedures and understanding of HSCT is also constantly improving, an argument both for going forward with it and for waiting as long as it is other safe options..
If I knew how easy a transplant could be I would have been far more open for this upon my initial diagnosis of CLL del17p.
A second transplant is not something I wish for or look forward to, but with Richters looming it is not something I really worry about.
I also really look forward to having the feeling of being cured!
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