#ClinicSpeak: managing unrealistic expectations in relation to HSCT

We need a national debate about the use of HSCT to treat MS and we need to educate MSers about what to expect. #ClinicSpeak

I received an email from a colleague this week that stated:

“I saw a patient last week that I thought might be worth discussing on the blog. The patient had a self-funded AHSCT in Russia last year after doing badly on an injectable. She went into the transplant with the expectation she would be cured. A year after the transplant she has now developed a spinal cord relapse confirmed on MRI. To complicate matters her lymphocyte count is still around 0.8×10^9/L. She was absolutely devastated when I gave her the MRI results that the HSCT had not worked. It was worse for her than receiving the initial diagnosis of MS. I started my training initially in medical oncology. It reminded me of giving the news to young woman with breast cancer who had just finished six months of adjuvant chemo and at the end of treatment her scan showed new metastatic disease. This is not a situation I’ve encountered before but makes the point that although HSCT is a highly effective DMT, it is not a cure for MS as it is often sold to people travelling abroad to be treated.”

I think it is important to realise that until we know the cause of MS and how it drives MS disease activity we won’t be able to declare a victory over MS, i.e. say to someone that you have been cured. This is why I am always careful to use the term ‘potential cure’, simply because I am not 100% sure I know what causes MS. 

I get very upset when I hear stories such the one above. AHSCT is not a cure and a significant number of pwMS will relapse after having HSCT. NEDA rates at 3 years are about 75% and this figure will drop with time.

Please note there are a lot of Charlatans out there who promise pwMS a cure, take their money and are not around, or disappear, when the shit-hits-the-fan. To protect yourself you need to be careful. The following is a sensible information sheet that has been prepared by the MS Group in Bristol that explains what you need to do when exploring HSCT abroad.

I actively discourage my patients from going abroad for HSCT, because it is risky, expensive and you need follow-up post-HSCT. This is one of the reasons why Barts-MS have started offering it to our patients in London, but we have strict guidelines governing its use. Please note that the NHS does cover the costs of HSCT and MS is specifically mentioned in the NICE guidelines for bone marrow transplantation. In addition NICE is in the process of generating MS-specific guidelines to cover HSCT for RRMS. In short there is no reason for you to travel abroad. 

CoI: multiple

56 thoughts on “#ClinicSpeak: managing unrealistic expectations in relation to HSCT”

  1. A sad story but an important issue worth discussing. How would you manage this patient? Should she be offered another course of HSCT or another DMT? I am sure a lot of people with MS and neurologists the world over must be facing similar issues.

  2. Prof G, Thanks for your post. The level of desperation of people diagnosed with MS cannot be under-estimated. I was diagnosed at my prime – young children, dream job, sport for leisure. At the appointment with the neuro to discuss DMTs I was sat in the waiting room between a young women on double crutches who couldn't stop crying and a middle age woman (with soouse) in an electric wheelchair who had little function left. You wouldn't want to become progressively disabled so why would you expect me to. Your job with MSers is fairly simple – to stop them becoming more disabled and let them look forward to the future with hope to live their lives / dreams. Treatment should be focused on those goals and patients not wanting such treatments should be counselled about the likely outcome. We have a mish-mash of treatments for relapsing MS which offer a range of efficacy and potential side effects. I know that some patients have done well on HSCT. i wish the researchers could focus on those who have breakthrough disease on HSCT, Alemtuzumab etc. I'm convinced that understanding this would provide some real insights into what drives relapses. Thanks for all your efforts.

  3. It is not that simple to access BMT under the NHS. My neurologist said no when I asked him. He also rarely prescribes Lemtrada or Tysabri, which he keeps in reserve in case they are needed later on.

    1. Needed for later after the damage is done.It is interesting that some people returning from Mexico are recieving rituximab. One wonders if this will give the main benefit.

    2. "rituximab. One wonders if this will give the main benefit."According to the black swan theory it shouldMemory b cell Memory b cell Memory b cell Memory b cell Memory b cell Memory b cell Memory b cell Memory b cell Memory b cell Memory b cell Memory b cell Memory b cell Memory b cell Memory b cell Memory b cell Memory b cell Memory b cell Memory b cell Memory b cell Memory b cell

    3. Nice post Dr GiovannoniUnfortunately this is a very difficult situation and only one patient Also if the patient was treat with your "high efficacy" drug of choice Alentuzumab and had new spinal cord lession what would you do? Do you post it on the blog also ,How do you treat her?Would like to know what "high efficacy" have NEDA rates at 3 years of 75% and their side effectsThanksLuis

  4. Hmm, put nothing has been proven to prevent progression in MS. Relapses and progression are different pathological things.

  5. "It is interesting that some people returning from Mexico are recieving rituximab. One wonders if this will give the main benefit."But is that not looking at it from the wrong angle? While HSCT must be the most brutal sledgehammer, the problem is the associated risk. And the equally brutal fact that it doesn't always work.And although it's all about taking high efficiency DMTs on this blog, the risk/benefit ratio of these isn't going to be suitable for everyone either, for a whole host of reasons.

  6. Thanks for this Gavin. Having had HSCT in 2010 as part of a clinical trial (HALT-MS), I try to educate others interested in the procedure as best I can. But being a voice of reason on this topic is akin to volunteering for human piñata duty. My video interview a few days ago with Shift.ms (posting soon) repeats most of what you've said, only from a patient perspective. I hope people can put down the bat long enough to listen to what I have to say.Dave Bexfield, ActiveMSers

    1. Hey Dave, thanks for doing all that you are doing. I've been subject to the piñata treatment at times as well. Not fun, especially when is there is so much bad info being passed around on various spots online.Seems anybody not adhering strictly to the party line is kicked out of the party. This is a huge disservice to all the patients seeking information on HSCT as well as other therapies; they generally only hear one side of the story. As you know, I'm an advocate for HSCT, but only for properly selected patients. Unfortunately, that message is not one that the gatekeepers want to let through the gates.Hope you're doing well, brother…

  7. Unfortunately HSCT is only available in the U.K. and Australia under very strict criteria, which the majority of people with ms do not meet. Then when other high-efficacy DMTs are often with-held by neurologists, what do you suggest patients do? Is it any wonder that they travel abroad to receive the treatment inaccessible in their own country.Not everyone who travels abroad for HSCT is an uneducated desperate patient unaware of the risks. Many set up post treatment care under a haematologist back home and have realistic expectations. HSCT offers them a far better success rate than DMTs accessible to them in their own country. With HSCT becoming safer and more refined, why wouldn't they pursue it?Until you as neurologists can give your ms patients a prognosis, you should be allowing them more of a choice in their treatment. Not all will pursue HSCT anyway, but for those willing and informed, it should be an option.

    1. Very well saidWe are todayvery far from the close to 10 % treatment related mortality that was reportedin early years. In fact, we saw no mortality or life threatening adverse effectsamong the Swedish patients. We have come to a point when adverse eventsoccur so rarely, that they are hard to measure accurately.A third hindrance is that patients and neurologists adopt a wait-and-seeapproach to MS. It usually takes several years before MS start to manifestitself with permanent disability, and many patients and doctors do not takeMS seriously until then. In fact, most of the requests for transplantation areself-referrals from patients with progressive disease and EDSS ≥ 6.These hurdles are not insurmountable. Newly diagnosed patients shouldbe continuously and carefully monitored to evaluate disease activity andtissue damage. Non-trivial disease should be hit hard and hit early. Patientsand doctors need to be educated, in order to disperse prejudices against thetreatment. Data from a phase III trial would be helpful to convince theskeptics and to establish the therapy as a second line treatment. We arecurrently participating in one (ClinicalTrials.gov Identifier: NCT00273364).Meanwhile, every wheelchair is a failure and every premature death is atragedy.Joachim Burman

    2. Very well said. You capture the issues with proposed solutions that need the various egos to swallow some pride and move forward

  8. Will pwMS that do HSTC and have relapses have a relapse because they would have some type of deficiency in the production of GH (growth hormone), either in the endocrine (in the pituitary gland) production or in the local production of GH in the immune cells?And GH has a connection with Vitamin D, because it seems that those who have Vitamin D deficiency may also have GH.If so who has Acromegaly would be free of MS?I didn't know this until I talked to an endocrinologist doctor, what is my friend, who said that in some children treated with GH for dwarfism they had suppression of the immune system, mainly of the B cells.

  9. Dr. G, how does therapeutic lag play into treatment with HSCT? Retrospective studies suggest that patients with progressive disease fared considerably less well with HSCT as those with relapsing disease. I noticed that the British inclusion criteria for HSCT in MS patients includes only PPMS patients with enhancing lesions. Do you agree with this assessment, or, based on therapeutic lag, would you postulate that HSCT could be of benefit to all progressive MSers?

    1. If the disease is totally burned out I don't think HSCT can help, but for everyone else with any inflammation whatsoever it can certainly be of benefit. Gavin has noted though that you must factor premature ageing into progression. We have neural reserve to protect ourselves from ageing but MS will burn up that neural reserve very quickly, leaving even relatively young people vulnerable to premature ageing of the nervous system.

    2. WK I think therapeutic lag is a general phenomenon and will apply to HSCT as well. Another factor that needs to be remembered is that the damaged CNS in people with more advanced MS (formerly know as progressive MS) handle the chemo less well; it is neurotoxic.

    3. The theory of therapeutic lag is relatively new so not everyone accepts it as fact. I would guess that we are at about 20% on the adoption curve.

    4. Thanks for the reply, Dr. G. The problems associated with advanced MS are quite the tangled web. Seems we need a master at untying complicated knots, before they become hangman's nooses.Not to go entirely off-topic, but any thoughts on the BCG vaccine for use in autoimmune diseases? Seems to work on the genetic level to down regulate some of the genes responsible for autoimmunity. They are doing trials in Boston using the vaccine on type I diabetes patients, but the hypothesis is that this will work on a wide spectrum of autoimmune diseases. I know there was some work on this in MS about 20 years ago…Still interested in doing an interview for WK? Would be most grateful if you are…

    5. What about hidden inflamation? We know that MRIs do not tell the whole story.Looking for disease activity especially "active" lesions is real guesswork and akin to spinning a blindfolded blind person around and giving them a set of darts to aim at a board.

  10. I'm not much of a gambler, but I know my maths… if I'm betting my brain… I want the best odds. Right now it was alemtuzumab… The bet seems to have paid off with a couple of years feeling completely healthy and clear MRIs…but in case things go south there's no 3 round of Alemtuzumab or HSCT in Spain healthcare… what option do we have? Its going for HSCT tourism and give it a shot, or let the disease consume us, that's the blunt reality… And most of us are not in the mind of giving up just yet.

    1. There are 2 centres in Spain already transplanting MS patients within your state health care system! They are in Barcelona, Navarra & Valencia. Just research on Facebook Groups.

    2. Pedro Oritz – in the scenario you describe how is going abroad for HSCT your only option? You can probably for a lot less money and risk just go abroad and have a third round of alemtuzumab or pay for it privately in Spain..??

    3. But if you need a third round are not flogging a dead horse? Cost and risk is one thing but getting worse and flushing money down the toliet on Alemtuzimab is another.What are the timeline remission rates for those that have had a 3rd round of Alemtuzimab Dr G?

  11. It is clear the level and competency of MS treatment is weak and variable (ref comment above re Tysabri etc being available only later – let the patient decide, it might be nice!!)HSCT has had excellent success but the Western world is sadly behind the times and quite conceited in its acknowgement of work done (800+ post trial patients in Russia) elsewhere ("dangerous centres" pfffff…).Mexico patients have Rixumitab as that is part of the protocol that can not be completed on site and needs spacing post transplant and engraftment.My main question is why the neurology profession seem to accept patient decline with no remorse or sense of responsibility when HSCT exists. It makes patient and economic sense. Though the fact only c21% pwMS are on a DMD shows the UK neurology profession are sleep at the wheel.

  12. "My main question is why the neurology profession seem to accept patient decline with no remorse or sense of responsibility when HSCT exists"Simple. Its NOT their Brains

    1. Spot on. Was just out in Moscow (aka "Charlatan" land) having HSCT and there was Dr (not neurologist) from UK having it too as was refused in UK.For this blog to call more highly qualified medical centres Charlatans is stooping pretty low. The NHS could also learn about compassion too.BTW Uk will be a third world country soon so we will have to drop our arrogance and really look seriously at what is really being done elsewhere.

    2. Was just out in Moscow (aka "Charlatan" land) having HSCT and there was Dr (not neurologist) from UK having it too as was refused in UKlolllllllllllllllllllllllllllllllllllllllllllllllllllllllllllllllllllllllllllllllllllllllllllllllllllllllllllllllllllllllllllllllllllllllllllllllllllllllllllllllllllllllllllllllllllllllllllllllllllllllllllllll

  13. Another case study for you:48 yr old female diagnosed RRMS June 2015. No warning, sudden big relapse. Discharged from hospital with no information or support.Appt with neurologist October 2015. Patient requests Alemtuzumab. Neurologist refuses, wants to offer Tecfidera,Neurologist appt Feb 2016. Patient bullied into trying Tecfidera, neurologist says disease is "mild" and EDSS 1 (no full assessment). Patient leaves appt in tears. Duly tries Tec but side effects intolerable.No further support, neurologist appt or alternative DMD suggested or discussed.Patient carries out own research / due diligence arranges UK referral for second opinion.Feb 2017 – new neurologist diagnoses SPMS EDSS 6 (less than 2 years after initial MS diagnosis)What choice does this patient have now, aged 50 with rapidly developing SPMSAnswer: she does her research, she becomes her own best advocate and she decides on the course of action which gives her the best chance of a future worth living.1. She chooses to have aHSCT because it is the only treatment which offers the possibility of halting the progression of her illness ( and because she is not stupid, she is fully aware that it may not work, she may be a non-responder, or that it may even prove fatal)2. She chooses where she wants to undergo aHSCT based on experience of the centre; experience of the lead haematologist; treatment protocols; post treatment complication rates of the centre; date when the procedure can be carried out; in-patient/out-patient protocols. 3. After long and careful deliberation, the patient undergoes treatment as an in-patient in Moscow and receives treatment and care which can only be described using superlatives.4. The patient is home and recuperating, with the full knowledge that she may continue to progress, but also with fair odds that her disease could be halted.Which doctor of any specialty is going to tell her she made a bad choice. As an aside. The first medical procedure carried out this week by the NHS was a simple blood test. Patient had to advise the nurse to swab the site and use hand gel before going ahead with the cannula. Perhaps removing the splinter from the NHS' eye before criticising may be more helpful.

  14. Sorry but I have removed some posts on HSCT maybe they will be re-posted but as some posts have details of people doing the procedures, I would rather remove them for the time being, but I don.t have time to review them properly

  15. Seems it's ok to label someone a charlatan, but not to set out a clear, definitive history. Not worth the effort of reposting when censorship seems to be the order of the day.

    1. Its not about censorship, it is about reading the posts, so in the case of Bald is Beautiful above there is no need to mention moscow. So is this really a pwMS's journey or an advert from Moscow?

    2. Yes this is really a pwMS's journey. I am trying to highlight the lack of support and choice that we pwMS have. I don't understand why you would think otherwise and I am offended by the suggestion that my history laid bare is a cheap advert !

    3. Why did you mention Moscow in your original article above? Are there separate rules or non Drs treated as second class citizens in terms of freedom of speech?

    4. I did not write the post, but I imagine the person in the post went to Moscow.Freedom of speech is in the US Constitution we are not in the US and have no duty to post what seems like a rant.There is not discussion to be had.

    5. It was the following text from the original blog that started the Moscow refernces. Please ensure you read your own content.I received an email from a colleague this week that stated:"I saw a patient last week that I thought might be worth discussing on the blog. The patient had a self-funded AHSCT in Russia last year after doing badly on an injectable. She went into the transplant with the expectation she would be cured. A year after the transplant she has now developed a spinal cord relapse confirmed on MRI."

    1. It did name doctors. If ProfG wants to read and take up your offer then he can read the spam, it offers no real benefit for pwMS.

    2. So why did the original article quote Moscow? If you say other points are "advertising" Moscow surely it is wrong to criticise too?By the way there is a pure stem cell scam facility in Moscow as well as another facility.

    3. ProfG is on holiday too and may respond but I suspect not as there is nothing constructive in this thread.

  16. Any progress is of benefit to pwMS. We need our Drs to be thinking differently and trying to be ahead of the game (though catching up would be nice) so some encouragement and passion from pwMS should be welcomed.

  17. In defense of the keepers of this blog, many HSCT advocates are evangelical in their approach, and make unsubstantiated claims and, at times, pass along blatant misinformation.I'm a big advocate of HSCT for patients properly selected, who fit the profile of those most likely to succeed with the treatment. However, many of the more fervent HSCT advocates, who tend to dominate HSCT websites and Facebook groups, practically insist that this treatment will help almost every patient.As is often said, you're entitled to your own opinions, but not to your own facts. Numerous retrospective studies have shown that patients with highly inflammatory disease fair much better after undergoing HSCT than those with more advanced, progressive disease. One retrospective study found that 80% of RRMS patients were progression free at five years, but only 35% of SPMS patients could make the same claim. The study only included one PPMS patients, who experienced no benefit. I suspect that most of those SPMS patients who did experience benefit were still in the inflammatory stages of the illness.Clearly, those earlier in the disease course who have active inflammatory lesions and/or relapses stand to benefit most from HSCT. Many of the medical tourism sites will accept almost any patient, regardless of MS subtype and imaging/diagnostic criteria.The shame of it is that if one recounts these facts on HSCT centered sites and groups, they are quickly shouted down and sometimes even banned outright. Therefore, the full picture regarding HSCT is not on display on the sites, which is a significant disservice to those patients seeking accurate info on the treatment protocol.Again, I am all for patients fitting the profile to vigorously pursue HSCT treatment. Those with disease that is beyond the inflammatory stage, though, would be best advised to follow the old adage that discretion is the better part of valor, as even though the mortality rates have fallen into insignificance, there are still risks associated with undergoing HSCT.I also agree that the MS status quo needs to more fully explore and even embrace HSCT as a front-line treatment option. For the right patients, it's incredibly effective, and compared to even the "best" DMDs, it is cost-effective as well. High time for mainstream MS neuros to get on board…

    1. The terminology, stem cell therapy, ignites passionate debate in patients searching for more effective treatments and repair. Maybe call the procedure immune ablation and reconstitution instead. It's similar to the cloning fervor from decades ago. Somatic cell nuclear transplant has a much calmer effect.

    2. How will this help when we have the MIST trial? This is just playing a holding pattern while Big Pharma sort out a repair therapy and protect their shareholders.I have never known a DMD to undergo such a rigourous trial regime as HSCT seems to be having to be subjected to.Meanwhile time is brain.

    3. It depends on the trial design. The hsct trials are not blinded how rigorous is that.Ablative v non ablative could be interesting but it would build UK infrastructure and confidence.

  18. Interesting to see that the people complaining on here about censorship of posts are the same people that admin the Facebook HSCT groups that are 'closed groups' and thus block posts by anyone who has a different opinion to theirs.

    1. It is not censorship the people simply need to read blog rules, I am on holiday and haven't got the time to redact posts.It is clear that hsct is another emotive issue like ccsvi, a thing you can do without neurologists

    2. Actually, it was me that complained about censorship. I am a pwMS and not an admin on any HSCT site

    3. Your posts were all launched so not sure why you are complaining of censorship. The post of Mindy was not posted as it mentioned names of people.

  19. Take that back the one where you identify yourself was not launched.However I did not spam it it must have happened automatically

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