ClinicSpeak: why my MS clinics are running late

When will interest in HSCT as a treatment for MS subside? #ClinicSpeak #MSBlog 

“I my clinic ran very late yesterday as I had to spend a lot of time discussing HSCT with several patients. Interestingly all these patients had early progressive MS and were realising that the DMT they were on was not doing the trick in that they were clearly getting worse. This is when pwMS look elsewhere and HSCT is one of the treatments out their with a lot of ‘evangelists’ singing its praises. I say evangelists because we still don’t have a well-defined risk:benefit ratio with which to compare HSCT with our other high efficacy therapies. Unfortunately, both grant applications that we submitted to the NIHR for funding earlier this year were rejected. The NIHR wants the UK MS Community to come together and to submit only one application.”

“It is clear from our blog analytics (page views and comments) that HSCT (hematopoietic stem cell transplant) is a hot topic at the moment. The BBC Panorama programme earlier this year on this topic has a lot to answer for. It is interesting to note that as far as Google Trends go interest in HSCT appears to be quite country specific; notably the British are searching frequently using the search terms ‘HSCT’ and ‘multiple sclerosis’ trends.embed.renderExploreWidget(“TIMESERIES”, {“comparisonItem”:[{“keyword”:”HSCT + \”multiple sclerosis\””,”geo”:””,”time”:”today 12-m”}],”category”:0,”property”:””}, {“guestPath”:””}); trends.embed.renderExploreWidget(“GEO_MAP”, {“comparisonItem”:[{“keyword”:”HSCT + \”multiple sclerosis\””,”geo”:””,”time”:”today 12-m”}],”category”:0,”property”:””}, {“guestPath”:””});

“HSCT is simply bone marrow transplantation or BMT rebranded. There is nothing magic about HSCT; HSCT simply speeds up bone marrow recovery post-immunoablation.  There are different intensities of immunoablation. So called myeloablative therapy is aimed at wiping out your immune system completely and replacing it with a new immune system. Non-myeloablative therapy is less intense in that it simply depletes your immune system partially and allows it be rebooted (partially). The non-myeloablative therapy is clearly less risky than the myeloablative therapy, but less effective. In other words more pwMS have recurrence of their disease activity after non-myeloablative HSCT, when compared to ablative-HSCT (A-HSCT).”

“The treatment in the BBC programme was non-myeloablative HSCT (NM-HSCT). This is why the treated MSers didn’t look too bad. The chemotherapy that is used for NM-HSCT is less toxic. Many in the field believe that if you are going to treat MS with HSCT you need to go the more aggressive route and use the more toxic and risky A-HSCT. They argue that NM-HSCT is not really better than the current high-efficacy drugs we are currently using to manage MS, i.e. alemtuzumab and/or natalizumab and/or ocrelizumab (still to be launched). One of the NIHR grants was to compare NM-HSCT with A-HASCT and the other NM-HSCT with the best high-efficacy DMTs as defined by the investigators (Nz/Alemz/Ocrz).”

“Please note the chances of dying from the NM-HSCT is in the order of 0.5%-2%; i.e. 1-in-200 to a 1-in-50. In addition there is the toxicity associated with the chemotherapy; nausea, vomiting, diarrhea, hair loss, bleeding, infections, infertility and neurotoxicity to name a few. The more disabled your are the worse the neurotoxicity. If you have lost a lot of nerve fibres already and have reduced brain reserve you handle chemotherapy poorly. The chemotherapy worsens neurological function. This is why a large number of BMT units have stopped treating people with progressive MS.”

“The seemingly miracle treatment effects of people in a wheelchairs getting up and walking is not unique to HSCT; we see this commonly with other highly-effective DMTs. Provided you have sufficient reserve capacity in the brain and spinal cord you will see spontaneous recovery from relapse-related disability once inflammation is switched off and recovery mechanisms are allowed to proceed. Anecdotes of Lazarus-like treatment effects has created unrealistic expectations for pwMS with more advanced disease. Please note that o nce you have fixed or progressive disability it is likely that you have lost much of your neurological reserve and hence even if you switch off inflammation with HSCT, or any other anti-inflammatory DMT for that matter, it is unlikely that there will be a major recovery of function. This is one reason why progressive MS trials have failed in the past. Therefore the benefit:risk ratio of HSCT changes with more advanced disease and its the reason why most HSTC trials are going to have age and disability cut-offs. This will need to be done to maximise the chances of getting a positive result.”

“So would I refer pwMS for HSCT? No, not as part of routine clinical practice. I would however be prepared to refer my patients to participate in a well-designed clinical trial to compare current treatments with HSCT. As part of the trial I would not expect my patients to pay for their treatment. The situation where HSCT is indicated as part of routine clinical care is the rare patient with MS with malignant, or very aggressive, MS that has failed all licensed treatment options. In this patient the benefits of HSCT out way the risks of the disease.”

CoI: multiple

21 thoughts on “ClinicSpeak: why my MS clinics are running late”

  1. It is the third most searched for keyword on our website Prof. G.We could stock up buckets of content on it to suck in page views but refuse do it as we feel it irresponsible especially given some communication have had with some real Stem Cell experts.What do I call a real stem cell expert?People who are very entrenched in SC broad based therapy. They folks who are understanding how, what and the nitty gritty details of SC's.Agree, people whos disease continues to progress and nothing is helping them rolling the HSCT dice is perhaps an only option.Others however well…Here's something that bothers me.Many (many) pwMS I communicate with and want or say they want HSCT are considering it "Just a procedure" with a minimal risk. Some even comparing it to procedures such as cardio bypass in risk assessment.Its MINDSET. These two above have no correlation what-so-ever for example.There is also the belief that its regenerative. Thats big.To pwMS who's disease course is not aggressive they truly believe, each and every one of them that its not "stop disease activity" but also, "it will be restorative."So, similar to what was observed in CCSVI. CCSVI may have some impacts re: cell oxygenation as blood flow in the brain is important. U of R here just put out a study saying 20% of all blood oxygen is used by the brain (basically).The regeneration in HSCT is not necessarily stem cells making new neurons, not likely. But thats exactly what most people think .vs. NEDA allowing for natural restoration (pruning etc.)If it were posed to pwMS Ocrelizumab is as effective or more effective at stopping disease activity .vs. HSCT people will still want HSCT as they think its restorative due to media and general SC media re: stem cells.Attempts to diffuse all this are happening in the global SC research community but its not working.Media… Even specific media towards MS continues produce hype articles on HSCT. Thus the websites where people are going to read about MS happenings are producing this content. It makes for page views, it makes for money and apparently responsible reporting is out the window. They dont care about patients they care about money. Even have patients producing it by gosh.Its like a zika virus of misinformation or incomplete information.Lets explain HSCT in 8 paragraphs or less.Can you imagine facing cardio bypass based on 8 paragraphs or less or glioblastoma?That media is making HSCT like a pill. pwMS sock away at the side effects, efficacy, disease progression of DMT's. How MS altered their lives. HSCT is is promoted as "Welcome to Oz where dreams come true."List out all potential side effects of immunoablation. Of stem cells gone wild etc.Here's what simply WHIPS me up:People think they do this and life will in time go back to more normality. Perhaps so. But they believe rehab post-HSCT is nothing. Where-as diet, exercise, lifestyle changes are still advised and in order. Yet, many wont do that now to try and make gains!I would say 80%+ of pwMS I communicate with who change the way they live feel better. Some, WAY better. But that 80% represents perhaps 1 in 100+ people. They either dont try or dont stick with it.

  2. Ooo…Incidentally the only way this changes:1. As you said, real science, controlled studies, MULTI-DISCIPLINE monitoring at more than a rudimentary fashion and proper dissemination of results by multiple entities .vs. closed ended dissemination of data.2. Researchers in MS, and SC experts (not HSCT but actual stem cell researchers) make a concerted and unified effort to get the realities into media entities. Sustained. CCSVI is still out there with people saying, "Cure." But most folks now realize, at best, symptoms relief to some level.3. Nations governance turns around and says, "Anyone who is encouraged into this procedure and does not see results will be refunded in full." As fast as SC clinics have popped up they will disappear.4. The patient associations start pressing on this. The realities. Instead of the definition and reporting of studies and occasional "Its a miracle story." put out the real risks, what SC researchers (not practitioners/providers) have to say and what is really involved.If people REALIZE that even with HSCT guess what? Need change diet, need exercise, need do ALL the things that CAN DO in many cases right now then perhaps they will DO those things.I dont enjoy working out on my total gym per se. I dont enjoy using the treadmill. I dont enjoy drinking down my spinach, walnuts, greens, almond milk, berries, flax seed concoction. I dont enjoy using the exercise bike to the point where I hopefully stop before my core temp rises and I begin to turn into a mass of conflicting impulses. But I do it.I know a handful+ of pwMS who have went through HSCT. They dont like onlining about it as all they get is barraged.One of them had aHSCT in Mexico. Immunoablation. Guess what? 4 months after DX'd with cancer.Chemotherapy and stem cell implant towards cancer is mainly towards blood cancer(s) as I understand it. She apparently had beginnings of a form of lung cancer and because her immune system was ablated it just "took off." Now she is undergoing therapies that made her MS appear as a walk in the park.News wont report this stuff. People dont want read that sorta stuff.They want have hope and who can blame them?But that said hope already exists. NEDA based on DMT and lifestyle changes towards wellness. Its the last part "work" they dont care do.Speaking of "work". One recent study said, "6 in the cohort returned to work"What work did they do before and now?One person I know returned to work too. He was in construction. He now stacks light weight consumables with breaks at a retailer during closed hours. Thats a pretty big difference. Dont get me wrong, he's grateful his MS is NEDA. But he is not happy that MS still took his career away. He's not happy he had to borrow $130,000 against his home to get the procedure which is now why he works at the retailer to pay it. He did see functional gains. At the end of each night of work he is COMPLETELY SPENT doing work that you could do and spend a good 4 or 5 hours of wake quality time. Not him. He comes home, crashes. Gets up, breakfast, coffee, workout. Few hours quality time. Back to it all over again.Told me come the weekend he's good for 1 day. Saturday he is too spent to do much anything.He actually wanted speak to mass media about it. They wanted only speak towards "the miracle."We have asked him if he wants us put it out there but we have told him the reality. Expect to be attacked. He's still considering it.

  3. Thank you for this very clear and informative post about NM-HSCT and A-HSCT. Do you have death rates for A-HSCT? The post suggests they would be higher than for NM-HSCT.My other comment about HSCT would be that some people with MS have an almost religious belief that they can be 'cured' by HSCT. This would have been fed by Panorama programme but it comes from something much deeper – perhaps the human ability to hope when there is no rational reason for hope? I think you have seen the same kind of belief associated with CCSVI treatment in the past. Incidentally, having to pay a lot for HSCT or CCSVI treatment convinces some people that they are getting something of great value, rather than making them question what they are paying for.

    1. Re: Death rates. For A-HSCT the death rates are probably in the 1-2% range and for NM-HSCT they are lower than 1% and in good BMT units even lower than 0.5%.

    2. Re: "'cured' by HSCT"I discussed cure in the past and it will take many 100's of subjects followed for 15 years or longer to prove, or disprove, this belief. I have discussed the definition of an MS cure many times before on this blog.

    3. Re: "perhaps the human ability to hope when there is no rational reason for hope?"Yes, the human brain is hard-wired to be optimistic. I use the gambler’s dilemma as an analogy. No gambler places a bet, or goes into a casino, to lose money; they always believe they are going to be the one that wins the jackpot. No person will sign-up to HSCT believing that they are going to die or develop complications. However, there will always be the unlucky ones who have the serious complications and occasionally die from the procedure, or develops serious delayed adverse complications. If you decide to go into an HSCT trial, or receive HSCT as part of routine care, you need to ask yourself the question what if I am the unlucky one? Am I am ready to leave my family and loved ones prematurely? If you answer yes, and yes, then you are ready to take the risks. In the same way I always tell my patients who sign-up for alemtuzumab treatment that they should expect to develop a secondary autoimmune complication; if they don’t they should count themselves lucky. if they are not prepared to develop a second autoimmune disease then shouldn’t be treated with alemtuzumab.

  4. I totally understand the concern about all this ancedotal stories about HSCT in Russia and Mexico, but can someone explain how representative the Ottawa results for A-HSCT was? That seemed to be a proper, controlled, procedure within a proper Hospital – hence the 'gold standard' of HSCT. Does that not suggest that HSCT could be a useful last-chance option?

    1. Re: "Does that not suggest that HSCT could be a useful last-chance option?"Yes, it does which is why it is an option in the UK under the NHS. But as it is cheaper than licensed DMTs we may want to offer it as an alternative treatment to say alemtuzumab. For the latter we need more data, particularly safety data.

    2. For the latter we need more data, particularly safety data. But would the data not be skewed if the patients are those who have exhausted all other opportunities, namely they are the most at risk and more aggressive MS. Also would this not be a relatively small subset of pwMS compared to those on things like alemtazumab, hence it will take longer to get to a stage where a valid comparison could be made. My concern would be to ensure that its a level playing field.

    3. Re: "But would the data not be skewed if the patients are those who have exhausted all other opportunities, namely they are the most at risk and more aggressive MS."No our proposed trial is not to study this type of patient, but patients with active MS who are considering Alemtuzumab. They would then be randomised to Alemtuzumab or NM-HSCT or Alemtuzumab.

  5. This commentary discusses HSCT and how it is probably not a great suggestion for people who are already progressive. What are your thoughts on HSCT for pwMS who are in the earlier stages of Relapse-Remitting MS? Assuming someone was JCV+ and the risk of death was approximately the same with natalizumab or A-HSCT, would HSCT be a viable option?

  6. If I may… some thoughts.I think such a trial is a good idea and even better if Ocrelizumab were included in the mix.If however results win/loose/draw would be thought to impact the hype I very much doubt that would happen. Again, most pwMS tend to believe its regenerative as well and almost all do not realize the same lifestyle changes they can make right now need be taken with HSCT.The HSCT world is not for whatever reason pressing that issue and its one of the thing that makes me say, "Now hold on a sec…"Before a person undergoes such a procedure want them really be strong as they can be. If a person is going to have chemo immunoablation and can get more fit before hand, given a blood cancer, thats what is warranted. I've never heard anything to the contrary and heard much that says, "oh yes…"It ONLY makes sense.If Joe/sephine Doe has 3 months until her cancer treatment is to take place he/she if they CAN get stronger are way advised to do so.Doesnt seem to happen with HCST. Why?Yet, afterwards, PT, diet, exercise, life management is advised.Not to be a pit in the fruit, WHY?Could it be that making said changes might result in patient saying, "Know what… I feel quite a bit better. Maybe not do this at least right now."Yet before similar procedure in blood cancer its advisable to get as strong as one can get.Would such a trial include multi-discipline monitoring of the SC patients? Probably not. Gets way more expensive. Yet, the medical professionals closest to said SC therapy in cancer and/or SC research should be the peep's watching for the potential side effects / impacts.I put that same question forth over and over and over in the recent Canada study. Not a single response. Ablating a persons immune system in force can have numerous repercussions not MS related.This would be a perfect trial for a place like UC Davis where many disciplines are brought to bare and thus data gathered is extremely granular.Since they are a leader in SC research then they would be seeking quantifiable data perhaps in all respects perhaps as a base to build off of towards other immune based SC therapies.UC Davis has a sized fight against Huntingtons Disease well underway. Perhaps a collaboration.Point being, they are a leader in SC research and may well obtain more knowledge in process. They also appear to have little in the way of issues in getting significant funds towards purposed research.Just a thought.

    1. Eh?HSCT for MS is managed by the same docs(haemo-oncologists), same hospitals, same departments and same hospital processes that carry out HSCT for cancer. Your claims that they don't follow the same process are absurd.In terms of fitness, you have to undergo a comprehensive series of tests to be eligible (heart function, lung/pulmonary function, liver function, kidney function, retinal exam, brain/spine MRI, venous ultrasound, ultrasound of digestive tract and spleen, full blood work up and microbiology, etc.). If you don't pass, you don't go ahead. Simple as that.PT is sometimes recommended afterwards as i) the patient has spent the last month in hospital (mostly lying around) and ii) chemo itself can cause some weight loss/muscle wastage.Diet changes are due to the patient being temporarily neutropenic (~3 months for NM-HSCT), so sensible to avoid high risk foods. This mild/temp diet change has absolutely nothing to do with MS.On multi-disciplinary follow-up post immune-ablation, this applies no more to HSCT than it does other immunoablative therapies like Lemtrada, Ocrelizumab, etc. Difference being with HSCT you'll have a periodic checkup with a haemo for life, and that they have 50 years experience/history and a couple million treated patients to go off. Far more than for any MS drug.As to your suggestion that docs refrain from advising these changes because they'd make the patient feel better and therefore cancel HSCT… Really??!I think you need to put your tin foil hat back on and go and sit quietly in the corner! 🙂

    2. "If Joe/sephine Doe has 3 months until her cancer treatment is to take place he/she if they CAN get stronger are way advised to do so.Doesnt seem to happen with HCST. Why?"1. My partner had cancer. When radiation and chemo was recommended to her, she wasn't told to get strong and fit. In fact it all happened so fast, there was no time for her to get 'fit' or 'strong'. If you take diagnosis as day 1, first surgery was day 3, second surgery as soon as her body partially recovered from her first and radiation and other treatment in between. She didn't have a blood cancer. 2. Who is going to tell an MS patient to get active and strong before HSCT? We saw 5 neuros in the time before HSCT. Not a single one told her to get fit or strong or what to do to prepare for the procedure.3. We had to request the referral to haemo from neuros it was not offered. My partner saw the haemo a month before HSCT. He organised an appointment with the nurse who went through all the preparations for chemo, including diet exercise mental health etc. Of course, by that stage, it was too late.I hope that clarifies WHY many MS patients contemplating chemo aren't getting told to 'get' stronger before HSCT.

  7. How does someone in the UK get assessed for HSCT treatment under the NHS? I am interested in being treated.

    1. i'm not a fan of hsct fb forums and i believe they need to be approached with a high degree of ongoing scepticism. having said that, i do believe there is a uk hsct forum with members who have taken an interest in exploring avenues for access within the UK. If you have the stamina for some effective brain washing, I believe you could access some logistical guidance. From what I understand, the first step is to get a referral to a haemo. I believe the forum provides guidance on who is who in the world of 'who may be prepared to make such a referral' if you meet the criteria.

  8. HSCT has been a hot topic for some time, certainly way before the tv program aired. I think patients are just getting better, or should that be louder at getting their voices heard. Why neuro's on the whole (I'm generalising here) seem to be so negative about it I don't know. As a patient I find it quite frustrating. Yes it has risks. You can die. All the DMT's have risks, none of them have iron tight efficiency either. You have to use the tools which are available and if a sledgehammer effect is the best there is so be it. I'm young, I want a functioning brain. I want to work,keep my independence and autonomy. I want to be able to pay my mortgage and ride my horse. These are the things which are important to me when considering risks. I'd rather live well and die young than a long life crippled with the effects of MS. Its come down to personal values and what matters to the individual. Life for me is about quality not quantity.It is I who carry the consequences of any actions I take. If in the future I decide to go for HSCT I'd rather do it with the support of my neuro. If that's not forthcoming I'll do it anyway as its my body, my life, my choice. Would I take HSCT if MS was not considered a critical illness, a disease which takes away your mobility and cognitive functions? A disease which can leave you isolated, fully dependent and in constant pain? Of course not. Yet these are the things you tell us MS can and does do. You tell us MS is a BAD Disease. When assessing the risks you need to consider the risk of the disease.

  9. These old posts got loads of comments at the time, perhaps the highest number of responses to any topic on this blog? All prior to the Panorama documentary being aired. Personally I think its the medical profession which has a lot to answer for, not the program itself which just raised a very basic awareness. When doors are seemingly shut on the topic people will look elsewhere, often this is towards social media. Allowing an open dialog as you are doing is a positive step forward.

  10. Of course it is the failure of the medical profession, like TTOMB said. Blaming the victims and the media is a cheap way of deflecting blame.

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