I post to manage expectations and counteract fake news.
There is a group of pro-HSCTers going around and saying HSCT is a cure for MS even in MSers with more advanced disease, i.e. it halts and reverses their disability. This is simply not correct and we have no published, peer-reviewed, data to support their position.
The meta-analysis below from Paulo Muraro and colleagues clearly shows that in MSers with SPMS and PPMS having HSCT the ‘majority of study subjects’ continue to progress. This is why most bone marrow transplant units generally don’t treat progressive MS. Even Richard Burt one of the main proponents of treating MS with HSCT stopped transplanting MSers with progressive MS when his BMT unit was still active.
The figure below from the Muraro paper confirms the above; over 60% of the SPMSers and 100% of the PPMSers worsened compared to about 45% of the RRMSers. Why? I suspect it is due to smouldering MS.
HSCT is simply a very potent IRT (immune reconstitution therapy) and is effective at switching off relapses and new focal MRI activity. We have no data to suggest that it impacts on smouldering MS. In fact, we have evidence to the contrary, that the chemotherapy used to deplete the immune system is neurotoxic and some patients actually develop worsening disability as a result of ‘chemo brain’ or acute neurotoxicity associated with the induction protocol. In the Canadian study, which uses myeloablative chemotherapy, treated patients lost more than 2% of their brain volume in year 1. Believe me, this is serious brain volume loss way above what you expect MS to do and is indicative of neurotoxicity. The reason why relapsing MSers cope with the HSCT conditioning is because of reserve and progressive MSers do not, because their MS has already consumed their reserve capacity.
Many years ago we showed that MSers undergoing BMT/HSCT release very high levels of neurofilaments as part of the induction protocol and the levels of neurofilaments released predicted worsening disability. In other words, the chemotherapy caused acute neurotoxicity and resulted in disability worsening. This is one of the reasons why the Rotterdam BMT unit, and many other units, stopped treating progressive MSers. However, if you go to a fee-for-service BMT unit they will treat all-comers. Why? It is called a business and money talks. Don’t be gullible.
What about the anecdotal cases of HSCT curing progressive MS? I can’t say I have seen a single case. All the patients in my practice with progressive MS who have gone abroad to have HSCT have continued to worsen on their return. I am aware of a case of a colleague of mine who had a patient who was in a wheelchair who had HSCT abroad who miraculously got up and walked after having HSCT. My colleague informed me that he had diagnosed this patient as having somatization disorder, a very common MS mimic, that is a psychiatric condition. I am, therefore, sceptical about miraculous anecdotes and I would urge you to be careful before you base your decisions to have HSCT based on anecdotes. What we as an MS community needs is published data on the risks and benefits of HSCT in advanced MS to base our decisions on.
Muraro et al. Long-term Outcomes After Autologous Hematopoietic Stem Cell Transplantation for Multiple Sclerosis. JAMA Neurol. 2017 Apr 1;74(4):459-469. doi: 10.1001/jamaneurol.2016.5867.
IMPORTANCE: Autologous hematopoietic stem cell transplantation (AHSCT) may be effective in aggressive forms of multiple sclerosis (MS) that fail to respond to standard therapies.
OBJECTIVE: To evaluate the long-term outcomes in patients who underwent AHSCT for the treatment of MS in a large multicenter cohort.
DESIGN, SETTING, AND PARTICIPANTS: Data were obtained in a multicenter, observational, retrospective cohort study. Eligibility criteria were receipt of AHSCT for the treatment of MS between January 1995 and December 2006 and the availability of a prespecified minimum data set comprising the disease subtype at baseline; the Expanded Disability Status Scale (EDSS) score at baseline; information on the administered conditioning regimen and graft manipulation; and at least 1 follow-up visit or report after transplant. The last patient visit was on July 1, 2012. To avoid bias, all eligible patients were included in the analysis regardless of their duration of follow-up. Data analysis was conducted from September 1, 2014 to April 27, 2015.
EXPOSURES: Demographic, disease-related, and treatment-related exposures were considered variables of interest, including age, disease subtype, baseline EDSS score, number of previous disease-modifying treatments, and intensity of the conditioning regimen.
MAIN OUTCOMES AND MEASURES: The primary outcomes were MS progression-free survival and overall survival. The probabilities of progression-free survival and overall survival were calculated using Kaplan-Meier survival curves and multivariable Cox proportional hazards regression analysis models.
RESULTS: Valid data were obtained from 25 centers in 13 countries for 281 evaluable patients, with median follow-up of 6.6 years (range, 0.2-16 years). Seventy-eight percent (218 of 281) of patients had progressive forms of MS. The median EDSS score before mobilization of peripheral blood stem cells was 6.5 (range, 1.5-9). Eight deaths (2.8%; 95% CI, 1.0%-4.9%) were reported within 100 days of transplant and were considered transplant-related mortality. The 5-year probability of progression-free survival as assessed by the EDSS score was 46% (95% CI, 42%-54%), and overall survival was 93% (95% CI, 89%-96%) at 5 years. Factors associated with neurological progression after transplant were older age (hazard ratio [HR], 1.03; 95% CI, 1.00-1.05), progressive vs relapsing form of MS (HR, 2.33; 95% CI, 1.27-4.28), and more than 2 previous disease-modifying therapies (HR, 1.65; 95% CI, 1.10-2.47). Higher baseline EDSS score was associated with worse overall survival (HR, 2.03; 95% CI, 1.40-2.95).
CONCLUSIONS AND RELEVANCE: In this observational study of patients with MS treated with AHSCT, almost half of them remained free from neurological progression for 5 years after transplant. Younger age, relapsing form of MS, fewer prior immunotherapies, and lower baseline EDSS score were factors associated with better outcomes. The results support the rationale for further randomized clinical trials of AHSCT for the treatment of MS.
Atkins et al. Immunoablation and autologous haemopoietic stem-cell transplantation for aggressive multiple sclerosis: a multicentre single-group phase 2 trial. Lancet. 2016 Aug 6;388(10044):576-85. doi: 10.1016/S0140-6736(16)30169-6.
BACKGROUND: Strong immunosuppression, including chemotherapy and immune-depleting antibodies followed by autologous haemopoietic stem-cell transplantation (aHSCT), has been used to treat patients with multiple sclerosis, improving control of relapsing disease. We addressed whether near-complete immunoablation followed by immune cell depleted aHSCT would result in long-term control of multiple sclerosis.
METHODS: We did this phase 2 single-arm trial at three hospitals in Canada. We enrolled patients with multiple sclerosis, aged 18-50 years with poor prognosis, ongoing disease activity, and an Expanded Disability Status Scale of 3.0-6.0. Autologous CD34 selected haemopoietic stem-cell grafts were collected after mobilisation with cyclophosphamide and filgrastim. Immunoablation with busulfan, cyclophosphamide, and rabbit anti-thymocyte globulin was followed by aHSCT. The primary outcome was multiple sclerosis activity-free survival (events were clinical relapse, appearance of a new or Gd-enhancing lesion on MRI, and sustained progression of Expanded Disability Status Scale score). This study was registered at ClinicalTrials.gov, NCT01099930.
FINDINGS: Between diagnosis and aHSCT, 24 patients had 167 clinical relapses over 140 patient-years with 188 Gd-enhancing lesions on 48 pre-aHSCT MRI scans. Median follow-up was 6.7 years (range 3.9-12.7). The primary outcome, multiple sclerosis activity-free survival at 3 years after transplantation was 69.6% (95% CI 46.6-84.2). With up to 13 years of follow-up after aHSCT, no relapses occurred and no Gd enhancing lesions or new T2 lesions were seen on 314 MRI sequential scans. The rate of brain atrophy decreased to that expected for healthy controls. One of 24 patients died of transplantation-related complications. 35% of patients had a sustained improvement in their Expanded Disability Status Scale score.
INTERPRETATION: We describe the first treatment to fully halt all detectable CNS inflammatory activity in patients with multiple sclerosis for a prolonged period in the absence of any ongoing disease-modifying drugs. Furthermore, many of the patients had substantial recovery of neurological function despite their disease’s aggressive nature.
Petzold et al. Evidence for acute neurotoxicity after chemotherapy. Ann Neurol. 2010 Dec;68(6):806-15. doi: 10.1002/ana.22169.
OBJECTIVE: Chronic neurotoxicity is a recognized long-term complication following chemotherapy in a range of diseases. Neurotoxicity adversely affects patients’ quality of life. The objective of this study is to examine whether there is evidence of acute neurotoxicity.
METHODS: This prospective study included patients with secondary progressive multiple sclerosis (SPMS-BMT, n = 14) and hematological malignancies (HM-BMT, n = 17) receiving chemotherapy as preconditioning for bone marrow transplant. The control groups included SPMS patients matched for demographic and clinical data (SPMS-PL, n = 14) and healthy controls (n = 14). Neurodegeneration was assessed at baseline and longitudinally (months 1, 2, 3, 6, 9, 12, 24, and 36), combining a clinical scale for disability (Expanded Disability Status Scale [EDSS]), a serum protein biomarker for neurodegeneration (neurofilaments, NfH-SMI35), and brain atrophy measures (magnetic resonance imaging).
RESULTS: Disability progression was significantly more acute and severe following chemotherapy compared to placebo. Immediately after starting chemotherapy, serum NfH-SMI35 levels increased in 79% (p < 0.0001) of SPMS-BMT patients and 41% (p < 0.01) of HM-BMT patients compared to 0% of SPMS-PL patients or healthy controls. In SPMS-BMT serum NfH-SMI35 levels were > 100-fold higher 1 month after chemotherapy (29.73ng/ml) compared to baseline (0.28ng/ml, p < 0.0001). High serum NfH-SMI35 levels persisting for at least 3 months were associated with sustained disability progression on the EDSS (p < 0.05). Brain atrophy rates increased acutely in SPMS-BMT (-2.09) compared to SPMS-PL (-1.18, p < 0.05).
INTERPRETATION: Neurotoxicity is an unwanted acute side effect of aggressive chemotherapy.
CoI: multiple
Hi Prof G,
Looking for a bit of help/advice. I am 72 and have either primary or secondary progressive MS, diagnosed 16 years ago. Pretty sure I never had RR, just a steady slow deterioration, now at the point where I’m in a wheelchair most of the time – very poor walking ability and shocking balance and getting worse. I had Copaxone in the early years when the Neuro thought I may have had RR but since then I have had no medication, Neuro says there is nothing he can give me which would make any difference. My question is: is this correct, that there is no medication that I can take?
Thanks, John.
” Hi Prof G,….My question is: is this correct, that there is no medication that I can take?”
Well you could take Ocrevus as its licensed..try it for sure but most likely it won’t help very much or at all.
G. will go on about brain health..sorry G. crosswords..foreign language..and exercise are no match for ppms.
Sadly there is little/nothing for progressive ms. I said as much and G. called me a cynic and said “blah..blah progress in ppms”..but all/most of responses agreed
with me. He never responded to my statement :
“It’s 2019..it’s MS were not talking ALS or PSP..still nothing for progressive that actually works. Admit it.”
https://multiple-sclerosis-research.org/2019/07/25-years/
Just to clarify at Barts-MS we think MS is one, not two or three diseases. In other words, relapsing and progressive MS are part of a spectrum and what dictates what you see clinically is reserve capacity. By the time you have advanced MS (aka as progressive MS) you have lost reserve and so you see a gradual loss of function. The latter is modifiable with anti-inflammatories but unlikely to reversible unless the mode of action is different. So yes DMTs, including HSCT, will work in advanced MS, but the treatment response is likely to be a slowing down in the rate of worsening and with time hopefully flat-lining or stabilisation of function. In addition, the treatment response is greater in systems that still have reserve capacity (arms > legs). When you look at the literature many DMTs have an impact on upper limb function, but not on lower limb function. This is why we are doing ORATORIO-HAND and CHARIOT-MS studies.
So, in conclusion, I think we do have treatments that work in advanced MS we just need to show they work so that we can get DMTs licensed and then for healthcare systems and payers to pay for them.
The HSCT community need to understand that we will only be able to get wider access to HSCT for MSers if we get good data that shows a favourable risk: benefit of HSCT that is cost-effective. Then we will get wide adoption of HSCT as a treatment for MS. This is why we are doing an NHS funded trial of HSCT vs. ocrelizumab/alemtuzumab, albeit in early MS. Payers rarely respond to class 3 and 4 evidence (anecdotes), particularly at a systems level.
Hi Prof G,
you mention there is a trial with HSCT going to take place… has this already started or is it still possible to try and be part of it? if yes, what are the criteria etc ? do you have a link?
many thanks
I dont think it has started yet and I suspect we dont know the final entry criteria. It will be a case of watch this space but we can do a post when its announced
Are you medically qualified to be giving people advice? No.
I know that there will be others who will comment on this, Gavin, and I’m going to try and keep my response brief as I’m unwell at the moment.
1. I’m not aware of anyone in the HSCT community that claims HSCT is a cure. Nor do we claim that it will reverse disability in progressive MS – we are focused on the halting of progression and any symptomatic improvements are a bonus. That is absolutely the stance of the HSCT community, so please don’t put words in our mouths or misquote us like that.
2. The research you’re focusing on here was an amalgamation of existing research spanning almost twenty years that was re-packaged as if to appear as if it was a new piece of work just a couple of years ago. There is more up to date research that’s been produced since then and Russia and Mexico who have treated more progressive patients than anywhere have been completely overlooked. What about their data? Have you met their doctors in order to form the very low opinion you have of them? I have. Russia is holding an international HSCT conference next month – Dr Burt will be speaking at it as well as Prof Snowden from the UK. HSCT specialists from all over the world will be speaking. Why would that be the case if they are essentially charlatans? It wouldn’t, would it?
Similarly, King’s have treated numerous PPMS and SPMS in the last 5 years – what about their data?
3. If you can draw on negative anecdotal cases of Hsct overseas, why do you choose to ignore the anecdotal cases of the successes that we know of – of which there are many more!
4. My husband wasn’t treated overseas he was treated on the NHS in London, despite having SPMS and no active inflammation. He forms part of their data, but is only one of many. If you choose to ignore the overseas data, why aren’t you willing to look a little closer to home at the work of Kazmi et al?
5. Burt absolutely DID transplant SPMS patients and he uses them as examples in his presentations. He sees reversal of disability as success, not halting of the disease! He has used examples of SPMS patients who have had their EDSS frozen after HSCT and claimed this is not successful. Why?
Really disappointed that you’re taking things out of context and presenting half a story here.
Alison, I and my colleagues and our MS clinical nurse specialists spend an enormous amount of time telling our patients with progressive MS that they are not eligible for HSCT and that contrary to what theu have read and/or being told HSCT has not actually been shown to work in progressive MS. I am not saying it won’t slow down worsening disability, but it is unlikely to stop worsening and it comes with much higher risks in people with advanced MS. This is related to neurotoxicity and a higher chance of infections, etc. If you disagree please publish the data to convince me and my colleagues otherwise.
Why on earth do you tell them that they aren’t eligible when the London AHSCT criteria state that they are?! You know that – you’ve published those criteria here, but here is is again anyway:
http://www.londonbridgehospital.com/LBH/treatments-specialties/stem-cell-transplantation/
As Boaz says, progressive MS can be treated with HSCT as per the EBMT guidelines under ‘Clinical Option’
To tell them that they aren’t eligible purely because they are progressive is untrue and misleading.
Why would you do that?
It is the 15-year disease duration criterion that does it for most of them and then the fact that most of them have inactive MRI scans and normal or low NFL levels on CSF examination. In other words we can’t find evidence of focal inflammatory activity.
I think that’s the answer to a different question, Gavin!
I asked why you tell your progressive patients that they aren’t eligible for HSCT when progressive MS is NOT an exclusion criterion.
In our centre, if you don’t have evidence of inflammatory disease activity you are not eligible for DMTs; this includes licensed and off-label DMTs and HSCT. Why should we have different criteria for HSCT; it is simply a more potent IRT. The use of alemtuzumab in older patients with more progressive disease in the USA may yet result in us not being able to use alemtuzumab 1st-line. Nobody seems to learn and adopt the lessons about the risks and benefits of the DMTs, even licensed DMTs.
That isn’t what you said. You said that you tell your patients that they are ineligible for HSCT if they have progressive MS.
Not true.
The London Hospital is private.
I’m delighted that you said that.
Why on earth would they be offering HSCT privately if it didn’t work for progressive MS?
Either because they know it does work and aren’t restricted in the same way as NHS practitioners, or…
But you’ll agree that the criteria are actually much the same as the London NHS criteria though? Progressive MS isn’t excluded from either.
I don’t know. Any ideas, Mousedoctor?
I couldn’t possibly comment 🙂
Really? I thought you had an opinion on everything?
Not like you to be stuck for words. 🙂
On advice from my lawyers 🙂
You have good lawyers if they’re advising you against saying something defamatory about why London Bridge choose to treat progressive MS privately.
Good advice! 🙂
What a load of poppy cock I have had HSCT in Russia,SPMS EDSS 4.5.I am now 5 months post,I was diagnosed in 2016 but have had MS since 1995 when my arm went numb and loss of coordination,between then and now I had my walking back,dropped foot gone,eyes 60% better,bladder and bowels much improved,balance nearl back to perfect,my improvements have been dramatic since HSCT.Im 68years old and went through the treatment by DR Federenko.I put all my trust in his expert hands because he is a Hemotologist,not like my Neurologist who was negative all the way,hence I don’t waste my time seeing him anymore.Helen
I left the HSCT community because of the “cure” posts. Also, studying research over a long period gives a larger cross section to draw conclusions from, I think that is why the data is so broad which is important. The bigger the sampling size the better.
Some patients do revert back to their earlier disease course from before HSCT after having HSCT, that is an unfortunate fact, but a fact nonetheless. HSCT is not successful for everyone which is why it should never be presented as a panacea as that can be very dangerous. There have been quite a few deaths associated with HSCT and people are prone to positivity bias. The decisions for IRTs need to be carefully weighed out and should not be misrepresented as they are risky and can have potentially fatal consequences. It is great that they work for some, but some is the key word. Glad HSCT worked for your husband.
A friend was involved in one the first Lemtrada trials and has remained progression free for almost 15 years now. That is amazing but it is also not a panacea and she went in knowing all the risks involved which are lesser than that of HSCT. It is important for folks to take everything with a grain of salt and to not rely on the word of a single good outcome as that is but a drop in the bucket as compared to long term studies such as the ones cited above. It is also important not to rely on the experiences of a few because the folks with good experiences are often the ones blasting it far and wide all over the internet as evident here where the ones with terrible experiences don’t or can’t. Best thing is to follow the data, read well thought out evidence, examine all the potential consequences and to make an informed decision devoid of emotions and anecdotal stories.
Lemtrada is currently under following new reports of immune-mediated conditions (caused by the body’s defence system not working properly) and problems with the heart and blood vessels with the medicine, including fatal cases.
*currently under review
Yep, the risks were still lower than that of HSCT as I mentioned.
That isn’t correct. I’ve specified the different risks in another reply on this thread. Lemtrada carries risks that HSCT doesn’t. The risk of fatal cytopenia, for instance, is higher with lemtrada.
Dr Richard Burt has actually referred to Lemtrada as “liquid HIV” a number of times. Now, he’s a world leader in the field of immunology, so it’s not unreasonable to assume that he must have a pretty good reason for saying that, and for preferring HSCT over Lemtrada?
One would think that Dr Burt would have the data to back up a statement like that.
Can you provide the reference to the study of HSCT to lemtrada please so that I can see where it was concluded
Because of a lack of validated scientific evidence for the treatment of progressive MS with HSCT we (Dutch MS patient association) follow the EBMT guidelines when informing our members. EBMT guidelines do state however when there is active inflammation (T2 lesions, OCB+ markers and/or confirmed clinical relapses) in progressive MS patients HSCT should be a therapeutic option. Hopefully high NFL levels as a biomarker will be added soon to warrant HSCT as a treatment option. However because of the failed CT in Rotterdam back in 99 when also 3 SPMS patients died because full myelo conditioning regime with TBI the Netherlands do not offer HSCT at all not even as a third line last resort treatment when nothing stops / halts aggressive malignant inflammatory MS. We will keep advocating that HSCT must be available in the Netherlands according to EBMT guidelines and reimbursed by health insurance to also avoid that patients go abroad to private clinics without JACIE accreditation and also miss the opportunity to correctly gather data on how these patients are doing after HSCT. Personally I have seen multiple succes stories of progressive MS patients treated aboard, however we do not have long term validated data to actually confirm these results which is a missed opportunity.
Prof G,
My question is similar to the first comment. Those with progressive disease (smouldering MS) are having any hope disintegrated by the various posts which have come out recently. Do we have any hope? Are there any therapies in trial that might help those with progressive MS? I can’t recall when you first put up your pyramid, but it’s disappointing that we haven’t moved off the bottom and now we are told that anti-inflammatory treatments are unlikely to have any impact on smouldering MS. I see that the MS Society has launched a fundraising campaign to ‘stop MS’, but I just get a sense of Groundhog Day – money raised, hopes raised, research funded, research negative…
Thanks
“Prof G,
My question is similar to the first comment. ”
“Do we have any hope? Are there any therapies in trial that might help those with progressive MS? I can’t recall when you first put up your pyramid, but it’s disappointing..”
Seeing as G. has ignored both your comment and the first comment I will fill
up the slack…Pay no attention to any pyramids or subway map treatments…
Nothing but idle hands of a burnt/out neurologist who can’t get a study funded…playing graphic design games w/imaginary neuroprotective drugs.
Atara Bio allogeneic ATA188 and autologous ATA190 are in trial and a hope for pms…there are BTK inhibitor drugs also…but the bio-therapy is benign as
it’s not a drug and only infusion of Tcells,
Initial efficacy: At approximately 6 months from initial dose, 4 of 6 patients in cohort 1 demonstrated clinical decline which was maintained at 12 months.
In cohort 2, an outcome classification of clinical improvement or partial clinical improvement was observed in all 6 patients at 6 months. No patients showed an outcome classification of stable or clinical decline.
http://investors.atarabio.com/news-releases/news-release-details/atara-biotherapeutics-reports-early-findings-potential-efficacy
This event and supporting materials can be seen on their investor page.
Atara Biotherapeutics ECTRIMS Conference Call: Atara will host a live conference call and webcast featuring Dr. Lawrence Steinman
http://investors.atarabio.com/events-and-presentations/events
Hello Prof G! I think it ‘s outrageous if a group of pro-HSCTers is going around saying that HSCT is a cure. Every pro-HSCT group that I have seen states very clearly that HSCT not only doesn’t work for everyone, but only aims to halt the progression of MS, any symptomatic improvements being a bonus. I say “only” aims to halt progression – that is huge for the patient concerned, but appears not to be sufficient for Dr Burt et all, who seem to require total reversal of disease for a success to be claimed.
I happen to have PPMS, diagnosed in 2009. I also happen to have had successful HSCT in 2014, over five years ago now. Did HSCT reverse my disability? No. But it was successful, because my disability, which was worsening rapidly prior to my having HSCT, has not worsened since 2014. That’s not possible, according to you, but I assure you that it’s true, and I have nothing to gain by saying so. I live in the UK, but not one single neurologist in this country offered any treatment for my PPMS. I found out about HSCT for myself, and had to go abroad to access treatment – quite a common predicament, and not only for patients seeking HSCT, unfortunately. Far from considering the foreign haematologists charlatans for treating international patients, you should be thanking them for saving the lives of your fellow countrymen who can’t access the help they need in the UK. You can quote all of the out of date studies you like, it doesn’t change the fact that there are many patients with progressive MS who benefit from having HSCT. If you are ever unfortunate enough to be diagnosed with MS I recommend that you consider it.
Re: “If you are ever unfortunate enough to be diagnosed with MS I recommend that you consider it.”
Yes, I would probably as a 1st-line therapy, but not 15+ years later when I am already disabled.
I think you might, if you were going downhill fast, with no other viable option!
You have spoken to a handful of people who have had HSCT and it hasn’t worked for them. That’s unfortunate.
I recommend your speaking to Dr Kazmi about his successful HSCT for progressive patients. You could also speak to Prof Young at the Walton Centre – she has at least 4 progressive patients who have had their MS halted by HSCT.
Just because you haven’t come across any success stories doesn’t mean that they don’t exist. If you won’t accept it from us mere mortals who have no business talking about Science, maybe you’ll listen to your peers.
I’m telling you that Dr Kazmi has data on this. Why don’t you go and talk to him and then come back to us?
I’ll wait.
You seem just a tad biased. I too have read and seen the information claiming that HSCT is a cure. HSCT isn’t available here in Canada due to the risk profile. Here they don’t prescribe Alemtuzumab to SPMS and PPMS due to a lack of reserve making them no more effective in PPMS and SPMS as the interferons. Perhaps if you read some of the other posts you would understand why they are not bothering to answer your questions. You can answer some of your own questions by doing a bit of reading. Also, you don’t need to be so darned confrontational, it is plain rude and makes you sound like a jerk. Seems like a lot of folks get stuck on a treatment that works for them and go on a crusade to flame everyone who doesn’t agree with them. Would be nice if you could keep your rudeness to yourself.
HSCT is available in Canada – in Ottawa through Dr Friedman – although possibly for not much longer. They offer the ablative form of treatment there, which has a higher risk profile. There’s a petition to keep the Ottawa HSCT programme going if you’re interested – but most patients tend to go overseas for non-myelo HSCT:
https://www.change.org/p/jack-kitts-save-the-ottawa-ms-clinic
Maybe do a bit of reading – you sound like a jerk when you make sweeping statements without the knowledge to back it up.
Just saying.
Since I can’t reply (no reply link for some reason), I’ll reply to myself, maybe you will see it. I don’t live in Ontario and have no health coverage for Ontario. So no its not available to me, I also don’t have the thousands and thousands of dollars required to get it. Personally I wouldn’t go for it as treatment.
My treatment has stopped my MS so there’s no reason to risk my life for HSCT. I’m not interested, sorry. If this’s what I have to look forward to in the HSCT “community” that other folks have mentioned I am glad I’m not in it.
That’s fine. Just making the point that it is available in Canada but that it’s not the same form of HSCT as is more widely available.
And the HSCT community isn’t obligatory! Nobody is held hostage there – people are totally free to make the choices that are right for them.
HSCT – or ANY treatment for MS – is very personal. We absolutely don’t dictate to anyone (in fact, you’ll see that statement from me in lots of groups). We are all about making HSCT visible and giving people the facts so they can make their own decisions.
I see much more aggression from the anti-HSCT brigade than I’ve ever seen in the HSCT community.
Classic reply! The only way you get to have it as a 1st line therapy is by going overseas… so where would you go Gavin?
I hear both Russia and Mexico are nice at this time of year. Well, any time of year if you want to halt your MS…
Wow, that one completely gave you away as an HSCT troll. Nicely done there lol
Ps. There are other IRT treatments with a somewhat similar efficacy profile (alem) that are not as risky but I don’t see you touting any of those… because you aren’t interested in the truth, you are interesting in winning your single minded crusade and bashing the docs in the process because you think you’re somehow smarter than the folks with advanced education in these subjects. That is very telling. Pray tell, where did you get your neurology, immunology, hematology degrees?
Why are you commenting under several different names? I might not have a degree in immunology or neurology, but I do specialise in language and syntax. Your style is giving you away, my friend!
Oh of course! You are fortunate to know about HSCT already – many MS patients aren’t even aware that there is a treatment that can halt progression, though, because most neurologists don’t mention it. It would be wonderful if every MS patient was offered HSCT as a first line treatment!
Read my post,Professor G,I’m a success story,68 years old SPMS,EDSS 4.5 I have had MS for 24 years,HSCT done in Russia.Helen
” but not 15+ years later when I am already disabled.”
You are entering Nazi/Eugenics territory w/ this remark..shows how just truly uncaring you are..Mexico does people up to edss 8.0 as long as they can transfer themselves. Asked one person at edss 8.0 and he said his improved bladder and brain fog removal enabled him to go back to work. Who are you to judge people’s quality of life..? No treatment for you..it’s too late for you now go wheel yourself away and die..this is unreal.
WTF? Eugenics? Get a grip. Prof G and this Blog have a focus towards improving the education and plight of patients. It is just that some people do not like the truth or the truth as far as we can tell.
There is a genuine risk vs benefit conversation to be had here. And people ACTUALLY DIE as a consequence of HSCT, if not suffer other consequences from the treatment. So the conversation must be had.
Mexico and Moscow HSCT are running businesses, remember that. And be careful not to drink the Cool Aid when you are there.
IT IS CLEAR… HSCT works in some patients with progressive disease, and has an impact on the inflammatory aspect of the disease, because it is a sledge-hammer immunosuppressant that results in a new repertoire of T-cells and B cells, plus other long standing effects(like possibly loss of T cell help leading to death of plasma cells, hence the OCB loss, but who knows).
This does not mean it works on any other aspects of the disease and in progressive disease with sick neurons it could be a death knell for these cells, especially with the more neurotoxic regimens.
Clearly the HSCT “cure” trolls have arrived as evidenced by your posse’s posts. After 30 years there is still no shortage of poppycock floating around about cures.
The research shows that when brain reserve is gone, the highly effective treatments are no more effective than avonex. These guys aren’t bad because you haven’t done your research, get a grip and stop being nasty online. Just because you think you can get away with it doesn’t make you not a jerk. There is a reason at governments in many places don’t license the treatment for SSPS and PPMS, the loss of effectiveness once brain reserve has diminished. When the effectiveness wanes, the benefit wanes and the risk is no longer worth it, that’s why governments in many countries won’t license it as a treatment for progressive MS. If you think they are all in on some big conspiracy too, you might want to make yourself a new tinfoil hat. When the early days of HSCT first started older and sicker folks died from it. If that isn’t reason enough for governments not to approve it for progressive MS I don’t know what is. You can’t blame these guys for the. Safety guidelines for it, duh.
This blog is generally for reasonable folks ruled by the land of logic, research and data, and generally not the illiterati.
Christine – do you know the difference between Non-Myelo and Myelo HSCT? You’ll find that the ‘folks’ in the Ottawa trials had myelo HSCT which does have a higher mortality rate.
Re- read your post – you’re accusing HSCTers of being rude, yet you’re actually the one being rude and disrespectful in the post.
so how about someone with 1 year’s diagnosis?
EDSS of 1?
on copaxone but still getting new lesions
should I just sit back and wait until I get a relapse that causes me to be paralysed from the chest down? Or unable to use legs and need to learn to walk again?
In reality I may as well just go and chuck myself off a bridge when I think about all the stuff I have to “look forward to” mightn’t I?
I don’t care what G. says about hsct facebook/internet groups…I believe you..congrats on being stable for 5 years…Amazing for ppms…if you’d gone to G. or like minded neuros you do realize at best you’d be wheelchaired..at worst you’d be institutionalized. Amazing.
Re: “I don’t care what G. says about HSCT facebook/internet groups..”
I have said nothing about HSCT/Facebook groups. The reasons for this post is the endless queries I get from my patients with progressive MS about HSCT and their misguided level of expectation about its efficacy in advanced MS.
A heartfelt thank you, Prof Giovannoni, for your brave and honest approach, advice. This blog is an invaluable source of scientifically sound sanity.
That’s rather insulting to the world class specialists who have successfully treated far more progressive MS patients with HSCT than GG has had in his office.
Haematologists are the experts in HSCT, not neurologists.
Do you think they just do it for fun?
Do your research.
I find your comment inappropriate and patronising. I have done plenty research and engaged my common sense. But I find your comments and conduct on here aggressive, unbalanced and will not be communicating further with you, or your group of zealots.
As a counter to our more, shall we say, evangelical contributors, here is Caroline Wyatt’s experience of HSCT for her MS.
I guess anecdotal evidence is acceptable when it suits you then? 🙄
like what?
Anonymous 1.18
A voice of reason.
Thank you
Oh dear check the stats in the Russian and Mexico files please,and just see for yourself and listen to a Hemotologist and not a Neurologist,Neurologists know nothing about cells only nerves.
But haematologists don’t assess and monitor disability progression so how would they know? It takes 100’s of subjects to be randomised to a treatment and compared to an active comparator and assessed in a blinded way to know if a treatment works. At present almost all of the HSCT data is unblinded.
So the data presented in the original post is legitimate, why? If you’re going to discount the Russian data, then you have to judge the data you’re seeming acceptable and reliable by the same standards?
Yep, that person is an HSCT evangelizing troll. The research shows the truth. This blog is pretty much always rooted in research and logic though some fun postulating occurs every now and then to keep things interesting.
Can’t say anything truthful about HSCT without the trolls coming out to bash away with their imaginary nonsense. It is sad.
Ps. Lemtrada (Alemtuzumab) gave me the hault in MS progression that I was looking for. It happened because I still had reserve left, if I hadn’t and I had already progressed to SPMS or had PPMS it would have had very little effect. I know this because of the RESEARCH and DATA on Alemtuzumab and on HSCT (both Immune Reconstitution Therapies). I suggest anyone reading the HSCT troll’s comments to go read the data as well because there is never a shortage of misinformation out there. Making a potentially life ending choice on a DMT/IRT should be made with all the risks known as well as all of the information and not on misinformation by some tool on a blog who is mad because this post’s title calls it like it is lol
The only trolling I’m seeing is from you, frankly. You’re very rude, and yet accusing anyone in favour of HSCT to be rude.
Lemtrada has been restricted recently, as I’m sure you know – EMA has started a review of Lemtrada (alemtuzumab) following new reports of immune-mediated conditions (caused by the body’s defence system not working properly) and problems with the heart and blood vessels with the medicine, including fatal cases.
As a stand alone drug, the clinical data so far has shown Lemtrada to be only 70% as effective compared to HSCT in treatment of relapsing MS. And Lemtrada has not been found to be at all effective in the treatment of progressive forms of MS as HSCT has been found very effective to halt all forms of MS, including (SP, PP) progressive MS. Lemtrada has a well documented treatment profile that is NOWHERE near as safe as HSCT. Lemtrada is responsible for fatal cytopenias in patients, and Lemtrada treatment comes with a shocking 30% rate of initiating a secondary autoimmunity. This compares with extremely low incidence of fatal cytopenia in HSCT (this is because of the use of a stem cell graft in transplantation to reinitiate hematopoiesis), and HSCT only has a risk of initiating a secondary autoimmunity in the 1-2% range. Lemtrada and HSCT are not comparable, as HSCT is both a safer and more effective treatment compared to Lemtrada.
They probably do not do it for fun. But judging at how much they charge and the nature of their advertising/website, they definitely do it for the/some money
Re: ” they definitely do it for the/some money”
Yes, it is a business, which is why they rarely so no.
This article and the responses make a bewildering read. Who and what to believe?
If I were you, I’d do my own research. Yes, read everything here, but there’s no substitute for self-advocacy.
You’ve got two sides of the coin here.
What’s definitely worth taking away from this is that most neurologists hadn’t even heard of HSCT until a few years ago – ours even asked if we could spell haematopoietic while he made his notes. Another, at the Sheffield HSCT symposium 3 years ago, readily admitted that he knew very little about HSCT and didn’t know what to tell his patients – other neuros at that event were nodding their heads in agreement. The haematologists at that event actually stood up and apologised to the MS patients present for their colleagues lack of knowledge and understanding. It was incredible. (You can hear the audio of that in the UK HSCT Facebook group)
Read as much as you can (research papers rather than opinions), but also talk to people who have had the treatment, and talk to the specialists who actually carry it out, as opposed to watching from the sidelines (that’s the haematologists, rather than the neurologists, for avoidance of doubt).
I respect and admire Gavin a lot, I think he’s a neurologist for all the right reasons and that this is a vocation for him. I also agree with the idea that you hit MS fast and hit it hard, but that doesn’t help those who have already progressed.
HSCT can and does work for people with progressive MS. Not for everyone, but to suggest it only halts progression in highly active RRMS is frankly B******s.
Thank you for taking the time to reply. I can see that a lot more reading is necessary. (It would be helpful if someone had done a systematic review of all the research papers but maybe they have.)
That is the subject of the post.
Not by a long shot it isn’t.
There is MUCH more data than this and there are many more papers to review.
Are you honestly saying that what’s been presented here is a complete, up to date, overview of the current research? Really? 😂
Try these groups for starters – you’ll find a lot more research (and links to research) in them than you will in this post:
https://www.facebook.com/groups/hsctworldwide/?ref=share
https://www.facebook.com/groups/ukhsct/?ref=share
https://www.facebook.com/groups/404629779644453/?ref=share
https://www.facebook.com/groups/mexicohsct/?ref=share
Alison, Mindy, Gwen- well said. Prof G – all fine arguments but the bottom line is that if you had MS, of any flavour and of any duration since diagnosis and you were told to go and live your life as best you can’, you would have HSCT in a heartbeat. The perfect academic scientific world you inhabit doesn’t reflect the lives of people who suffer with MS right now. We don’t have the luxury of waiting x years for god knows how many perfect empirical trial results. Get a grip and start advocating for patients in a balanced way.
It appears that the fact that Prof G goes out of his way to be balanced is the problem here.
No, the problem is that you’re not looking at the whole picture – you’re simply seeing what you want to see. It’s dangerous to dismiss anecdotal evidence when it’s on this sort of scale.
This is a lovely article which recognised the value of anecdotal evidence:
https://www.google.com/amp/s/amp.theguardian.com/healthcare-network/2012/sep/03/in-praise-of-anecdotal-evidence
“Prof G goes out of his way to be balanced is the problem here.”
No..the problem is he goes usual Pharma-crazy…”Medicine is an art..not a science”…”Even Pender has to use Pharma”…No…Pender’s first study was only 10 patients sponsored by MS Australia for $1 million..after that Pharma came to him and paid to license it in trials. Did the Raltegravir
pharma come to you w/$$$ for the EBV/MS trial..EBV/cancer experts could have told you that study was doomed. Did you ever reach out to them..? Did you guys really think you could beat EBV/MS with an AIDS drug..? More Pharma-Crazy-Ideas to come stay tuned in all you MS Kids.
Re: “HSCT can and does work for people with progressive MS”
Yes, active progressive MS, which is what this post is about. We have no data that HSCT works in advanced MS without evidence of ongoing inflammatory activity.
That data is available, Gavin. Speak to King’s. My husband’s case forms part of the data they hold. King’s have treated more patients for MS in the UK than anywhere else. My husband had no active inflammation and no new T2 lesions when he was accepted for treatment for rapidly progressing SPMS. He was experiencing new symptoms on an almost weekly basis before HSCT. Since HSCT – no progression and the reversal of many symptoms.
If you’re going to dismiss that, please explain why? King’s have treated other patients without activity.
Interesting, SPMS doesn’t rapidly progress, that’s PPMS. Perhaps he was misdiagnosed?
Certainly sounds like it.
Also what is the entire period that he was without T2 lesions? (For how many years did he get MRI’s and not have any new lesions). As I understand it, there is a significant time period for it to be considered non active. Would be helpful to take anything you are saying seriously if you would be courteous about it rather than aggressive, insulting and inflammatory.
As it stands a sampling of one is insignificant and you haven’t provided enough information to convince anyone, sorry to be blunt. Bees with honey and all of that.
King’s have data on many SPMS and PPMS patients treated; I wasn’t suggesting they take a sample of 1 as absolute proof.
It isn’t correct to say that SPMS doesn’t rapidly progress – the speed of progression can vary enormously.
My husband was diagnosed in 2011 with RRMS after experiencing issues on and off since perhaps 2009, when he had a bout of optic neuritis.
He had activity in 2011 on an MRI and steroids helped. He was subsequently diagnosed with SPMS, and progressed very fast in 2014/15.
To reiterate – King’s have the data. All they need to do is ask…
I (we) are being very consistent and treating HSCT as we do any other DMT. We have no evidence that HSCT works in inactive advanced MS (aka as inactive SPMS and inactive PPMS). Similarly, we have no evidence that cladribine works in the same patient group, which is why we are doing the Chariot-MS trial.
I have had inactive MS and have had HSCT in Russia,SPMS EDSS 4.5 and I have had many reversals,so yes it does work for us.
All that Prof G is asking is for the evidence that HSCT works in active SPMS and PPMS to be published so that he and other MS neurologists, the wider MS community and people with the disease can make an informed decision. Unfortunately, anecdotes on social media simply don’t cut the mustard. In fact, he has laid out his arguments to the contrary quoting and presenting published peer-reviewed data.
Thanks. This opinion is spot on and exactly what I am asking for.
I think that some people have lost sight that people with MS are more than scientific data and scientific research…. We aren’t rats or flipping monkeys!
We are real people fgs!
and as for the “I don’t do Facebook thanks” well, can you see the eyes rolling?
Re: “..We are real people fgs!..”
I agree and so would the EMA and FDA, which is why it takes class 1 evidence to get drugs licensed. The regulators don’t want doctors prescribing medications to their patients that are not licensed or off-label. The same arguments apply to procedures such as HSCT.
Yeah, but you are really stubborn if you don’t realize that this post is supporting PPMSers and SPMSers getting the data released that governments need to allow (and in some countries to even pay for) these treatments so they can access them.
You can try to paint these docs as bad as much as you want but the governments only okay medications on the basis of the data supporting it…. did it ever occur to you that’s why they are making a very public post about getting the data released? Likely not or you wouldn’t be being so nasty to everyone here who is working to the same goal (only with logic, reason and real significant follow-through and results in mind using an approach that might actually work).
I have no knowledge of HSCT ie whether it has any beneficial impact for those with progressive MS. I do know that the licenced dmts have very limited beneficial impact – even those that are licenced for PPMS or SPMS. As someone with RRMS on a highly effective treatment, I was disturbed to read Prof G’s position that a treatment like Lemtrada might be merely (by knocking out relapses) be converting someone from RRMS to PPMS. I do feel that MSers who read this blog are being left in limbo – we are stuck between a rock and a hard place. We either have no treatment option or have treatment options which come with a raft of risks and are not tackling smouldering MS (the real disease).
Is it possible to have a post which gives an overview of where we are on tackling the real disease eg anti-vitals, drugs to treat smouldering MS, drugs to address hot microglia, neuro-protective drugs, remyelination drugs, neuro-restorative drugs. I’m not in too bad condition at the moment, but will be on my way to Dignitas when I reach c.edss 8 (someway off yet). Are we likely to see any major advances on any of the above in the next 5-10 years, or will we still be stuck in the current dogma, or the one after that?
Is the data you’re using to show neurotoxicity and disease worsening post HSCT based upon myleoablative HSCT or non-myleo? Are there studies regarding neurotoxicity and disease worsening with non-myleo?
I stated the Canadian BVL data is from a myeloablative protocol. But the rapid year 1 brain volume loss occurs with non-myeloablative chemotherapy as well.
May I ask you what did you earn in bonuses from the Pharma company’s for putting patients on these toxic drugs? I know this information is available to the public on the net.
No it is not. As present it is voluntary in EU.
You may find out costing associated with interactions with pharma but it is not pay as a flight goies into that pot for example.
There is no bonus for an NHS doctor. It is also patient choice to take medication you do this with consent.
Could you please provide a link to study to support that neurotoxicity and MS worsening can occur following non-myleo HSCT?
Okay folks, we are in the 21st century now and due to the fabulous invention of the World Wide Web, the borders between countries barely exist any more.
Therefore I submit this published report from the AA Maximova hospital in Moscow for your perusal. It is dated 2015, which is a report that is older than I would usually suggest. However , it included 56 progressive MS patients in it’s cohort of 99 patients. This report was basically the culmination of 15yrs of dedicated work on HSCT for MS by the AA Maximova Hospital.
So for those who want clear, unbiased, peer reviewed, scientific data, that HSCT can halt the progress of all types of MS, just read the following report.
Any questions please feel free to send to me and I will raise them with Dr Federenko, Dr Burt or Professor Snowden, at the forthcoming symposium in Moscow at the end of November.
https://www.ncbi.nlm.nih.gov/m/pubmed/25711670/
PS. You are all welcome to attend the symposium. I think we may even have some Neurologists attending! 😊
Oh boy you have had fun today, it reminds me of the bad old days when we rabid CCSVIers used to descend on us to rubbish ProfG. Joan Beal was on his case then and I can clearly see HSCT-Joan has an easily identifiable moniker. We tracker Joan down and all chipped in and bought ProfG her CD. I wonder if he listened to it?
Perhaps you can enlighten our readers and me and find out what has happened with HSCT Chicago…looks like it is closed down and….Prof Burt has gone on sabbaitical. Where to Russia or Mexico?…Only joking:-)
He was very complementary about our B cell work when I met him. Although he uses anti-thymocyte globulin, it was clear it is an anti-lymphocyte serum.
I remember going to a HSCT talk many years ago when I was at Queens Square and there was a talk from a Top neurologist from Italy doing HSCT studies in MS. I remember giving him a hard time and asking if there was evidence that HSCT was stopping brain inflammation…He said he didn’t know, but I would not let it lie and said that the procedure had been killling people, surely it was known…After a prod in the back by an Italian Pathologist in the audience…I shut up. The Pathologist was marked for life:-)
However there are other studies and infllammation (smouldering MS) was not stopped.
“giving him a hard time and asking if there was evidence that HSCT was stopping brain inflammation…He said he didn’t know”
Well we do know now..it does stop it.. just takes 2 years.
In patients with follow-up time >1500 days, IgG OCB were detectable in 50% of patients, 14% had a pathological IgG index and none a pathological NFL.
CONCLUSIONS:
Intrathecal immunoglobulin production and NFL were lower after treatment with aHSCT, decreased over time and were normalised in a significant portion of patients. This challenges the notion that OCB are unaffected by therapeutic intervention in MS.
https://www.ncbi.nlm.nih.gov/pubmed/31347948#
edit above post it just takes 4 years…yeah..slow acting..
Not sure if you read the paper… but they treated a young group of patients and follow EBMT guidelines in Uppsala.
So RRMS/inflammatory disease of short duration.
Promising though.
Same can be said for Cladribine, and it has a much more favorable AE profile (https://www.sciencedirect.com/science/article/pii/S2211034818303687). Maybe everybody doesn’t need (a)HSCT. Just sayin’ 😉
If the most potent and efficacious neuroinflammatory, HSCT, does not stop progressive phase of MS, then how do you think cladribine, siponimod and ocrezulimab will fair in treatment of “active” progressive MS long term? Laughable, if it were not costing patients their livelihoods.
There is not one effective treatments that inhibit adaptive peripheral immunity that will stop progression of MS. HSCT and cladribine may have a partial effect as they cross the BBB and may work on EBV controlled memory B-cells in the meninges of the brain.
Until changes in innate immunity are addressed (EBV controlled B-cells, hot microglia, A1 astrocytes, oligodendrocyte changes and/or neuronal death), researchers will continue to produce disappointing results by repurposing or focusing on inhibiting adaptive peripheral immunity for profits.
Using NFL as a marker in progressive disease has also been shown to a waste of time as witnessed by the early ibudilast trials in progressive MS in which they have had positive clinical results but did not correlate with a decline in NFL levels. It seems only useful in acute neurodegeneration with RRMS.
The real or progressive MS remains mostly untouched by current immunosuppressant therapies on the market.
“Using NFL as a marker in progressive disease has also been shown to a waste of time ”
Wow…you sure about that.
“My brain is being destroyed but I have normal NfL” ..totally….IMPOSSIble
“indicating the man had entered the SPMS stage. In 18 months, his EDSS scores — which quantify disability and its progression over time— rose from 4.0 to 6.0 (severe disability), and had a nearly 4.5-fold higher levels of neurofilament light chain (NfL) ”
“Two year later, her disability had worsened, and her EDSS score was 5.5 (a level at which walking aids are needed for any distance). Laboratory analysis found such high levels of NfL in her CFS sample that were “off the scale” — more than 26 fold — and beyond accurate quantification).”
https://multiplesclerosisnewstoday.com/2018/07/17/cladribine-effectively-eases-progressive-ms-activity-uk-case-study-reports/
https://www.ncbi.nlm.nih.gov/pubmed/31123141
As they stated in this respected journal (:https://www.ncbi.nlm.nih.gov/pubmed/31123141):
CONCLUSIONS:
CSF NfL correlates with MS activity throughout the course of MS, reflecting the axonal damage in pwMS. Relapse is more strongly associated with elevated CSF NfL levels than the development of progression, and NfL may be most useful as a marker of disease ‘activity’ rather than as a marker of disability or disease stage.
Re: “NfL correlates with MS activity throughout the course of MS”
Yes, NFL levels are an inflammatory biomarker, which is how we use them.
“There is a group of pro-HSCTers going around and saying HSCT is a cure for MS even in MSers with more advanced disease, i.e. it halts and reverses their disability. This is simply not correct and we have no published, peer-reviewed, data to support their position. ”
One interpretation of this statement could be:
It seems that science is more and more disregarded and replaced by confirmation bias and public opinion making. Scientists have a responsibility in this when they design the trials in such a way to just prove their opinion and/or overinterpret their findings afterwards. What is needed is more scientific! proof, better trial designs, less public opinion making and better informed decisions with patients that should be based on real scientific evidence.
Thanks, came here to say this.
Hear Hear Prof G!
As an MD who has MS and just had HSCT (and I have a PhD in human immunology so have some understanding of both the disease and the treatments) it is unreal how blindly some people follow the notion that HSCT is a panacea.
I had to stop following some of the HSCT support groups because certain members took on the role of physicians and started answering all sorts of questions with cartoon graphs, acting like they were presenting data.
Prof G is 100% on point here, the supportive data does not exist for progressive disease as claimed by some. Maybe HSCT possibly helps slow progression in some patients (still something to pursue considering the alternatives!).
There is not enough evidence to throw around “cure” so freely. Everyone needs to chill out and look at the data for it has no emotion!
It weirds me out that so many people go in to bat for Moscow and Mexico, two centres who have no reason to be open about their results. Considering they apparently have treated thousands of patients leading to countless cures, why do they not count these cures, put together a manuscript and publish their findings!?
P.s Neurologists and doctors in general aren’t out to get you, this view seemed to be common in the OMS community as well(as well as amongst anti-vaxxers). Group-think is dangerous, avoid it at all costs.
MS is a crappy disease, just thinking that HSCT will cure it does not make it go away.
This blog is priceless and the reason why it seems harsh sometimes is because it is presenting data and views/opinions that are as unbiased and accurate as possible, and are in relation to a crappy disease!
“Maybe HSCT possibly helps slow progression in some patients (still something to pursue considering the alternatives!). ”
Sorry Doc and G. you got this all wrong….hsct never slows progression…those are dmt drugs…that pharma uses to cash in.
Hsct is on/off switch…problem is people relapse after 1,2,5,10 years.
ppms patient 2014 edss 3.5 hsct Russia edss down to 1.0
2017 ms back….2019 edss back to 3.5
Hey Anono,
I don’t think we have it all wrong, it doesn’t appear to be an on/off switch for many patient with progressive disease.
Again, look at the evidence, not just what people tell you on facebook groups.
You have had a good outcome, but this discussion is not about you.
Re: “ppms patient 2014 edss 3.5 hsct Russia edss down to 1.0”
I suspect this patient had active PPMS, I suspect this would have happened on ocrelizumab as well. It is all about treating early when you have reserve capacity that allows you to recover function.
Moscow HAVE published their results. In 2015, almost FIVE years ago.
https://www.ncbi.nlm.nih.gov/m/pubmed/25711670/
Hi Mindy,
In this study they have 35 patients secondary progressive, 18 pp and 3 “relapsing progressive” patients in their cohort. ALL of the patients outside of SPMS had disease durations of less than 15 years and the median duration in the SPMS group was less than 10 years(I wonder what the mean is?).
Firstly, this is a study lacking statistical power.
Secondly, the study has ZERO blinding or really any way of controlling bias of any sort whatsoever(sure it is open-label, but that reduces the scientific validity and the strength of the evidence is less than required for a paradigm shift).
Thirdly, considering the age of the patients in the cohort and the duration that those PwMS have had MS the findings presented support the sentiment put forward by Prof G. Treat early.
Why do people struggle so much healthy skepticism? Advanced MS can be a highly co-morbid condition, and caution needs to be taken, otherwise we will have people wasting their money flying to Russia and Moscow, coming back potentially worse off or dead because there was not appropriate critique of the data or requirements for self-auditing and transparency as seen otherwise.
Just remember, only 99 patients are presented here, which were excluded form the study and why?
This paper does not do much to convince me of anything new.
Nice post
Why did you choose to have Hsct?
How long do you have ms?
Thanks
Hey,
Diagnosed 2010.
I had elevated NFL despite being on rituximab.
Did not really choose it tbh. Was offered it, but it was a no brainer. Excuse the pun.
It is a confronting choice but after actually reading around the evidence and the risks vs other DMTs of similar efficacy, the likelihood of not needing further treatment and the likelihood of declining efficacy the longer I wait.
Also I have a supportive Neurologist and they provide excellent care in Sweden.
Great post, thanks for bringing back some logic and reasoning to this discussion, much appreciated! 🙂
Wow, what a discussion!
Just to let You know there is another group called HSCT non-responders that is trying to say it loud to the public that HSCT is not a miracle and it is not working for everyone. There are lots of comments in this group that are similar to the outcome of your post.
Unfortunatelly I’m a non-responder, had mine HSCT (CTX ATG) done five years ago in Poland. And relapsed last year again. Looking for the ways to stop the disease again I have recently started Tecfidera. If it will not work I will go for other ‘miracoulous’ DMTs as cladribine, ocre or… HSCT 2.0?
BTW. 5 years ago I have instructed my neuro what HSCT is and how it might impact/stop RRMS.
“Unfortunatelly I’m a non-responder,”
It worked for 5 years for you…you’re more a relapser it would seem.
Hi,
What ever it calls, a non-responder or relapser I’m back on this journey.
But HSCT was the best thing I have done so far, it has stopped my disease for 4 years and lowered my EDSS from ~5 to 2. And I’m still doing good physically. The hard thing is to find out what can I do next. I have visited 6 different doctors and everyone has proposed a different drug! So DMF / Ocrelizumab or Rituximab / Natalizumab / Alemtuzumab / Cladribine / Cyclophosphamide. I have just re-started to threat my MS with DMT as being newly diagnosed, but I know it’s not true.
Based on the graph above it looks like about 3 out of 10 people with SPMS are responders at 10 years compared to 0% of people with PPMS and 50% of people with RRMS. Overall these results are not overwhelming to me and suggest HSCT is only moderately effective. Is HSCT superior to alemtuzumab, ocrelizumab or natalizumab? I would like to know the answer to this question.
“Is HSCT superior to alemtuzumab, ocrelizumab or natalizumab? ”
Yes…because none work in progressive ms as none get in the brain.
CYC used in Mexico/Russia hsct does…was therapy as Revimmune.
Revimmune (high-dose pulsed cyclophosphamide in a proprietary system-of-care) was developed by researchers at Johns Hopkins University, which licensed it to Accentia Biopharmaceuticals, Inc.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3002608/
Re: “..CYC used in Mexico/Russia hsct does..”
The problem with cyclophosphamide is that it is toxic to the gonads. For a woman with MS, your risk of going into premature menopause is about 40-45% and if you are male you need to bank sperm as a security policy.
Banking oocytes delays HSCT treatment in a woman by about 3-4 months and then there is the cost of banking.
5th Congress of the European Academy of Neurology – Oslo 2109
A meta-analysis of autologous haematopoietic stem cell transplantation in MS
G. Mancardi; Genoa/IT
In the Italian experience, at 15 years after aHSCT, almost 60% of 160 evaluated patients did not experience disability progression. This proportion was significantly higher for RRMS (82%) versus SPMS (38%) (p=0.003). At 10 years
https://ipp-ean19.netkey.at/index.php?p=recorddetail&rid=1ae237a5-63e7-46c5-be89-0e4f00fbfaec&t=browsesessions
A conference you were in
😉
Some of the Italian HSCT data is included in the Muraro meta-analysis.
European academy of neurology 2019 oslo
Efficacy of autologous hematopoietic stem cell transplantation in secondary progressive multiple sclerosis
Results:
Patients: 15 females/5 males; median age at aHSCT, 37 (27–58); median disease duration, 11.5 years (6–20); baseline EDSS, 6.0 (4.0–7.0). At year 5 of follow-up, 14/20 patients (70%) experienced EDSS worsening (median 23 months after aHSCT), but 9/14 (64%) showed persistent interruption of disability progression following a single-step EDSS deterioration. Only in the remaining 5 patients (25% overall) disability maintained the progressive course observed at inclusion. Annualized R-BVL was higher in patients who progressed (median -0.45) compared to those who showed EDSS stabilization (median -0.14), although not significant. No other baseline features correlated with the clinical outcome.
Conclusion:
After aHSCT, stabilization of disability progression and normalization of brain atrophy were observed in 75% and 35% of the patients respectively. The absence of correlation between R-BVL and disability suggests that spinal cord involvement may play a major role in disability progression assessed by EDSS. These data suggest that in Pr-MS interruption of disability progression could represent an informative outcome measure of treatment efficacy.
https://ipp-ean19.netkey.at/index.php?p=recorddetail&rid=0916d6ae-3df0-4417-9f58-178ec4cfa89e&t=browsesessions#ipp-record-8dbb6a96-e285-414f-82f6-0a7fcd403ba7
A conference you were in
😉
RE: “At year 5 of follow-up, 14/20 patients (70%) experienced EDSS worsening (median 23 months after aHSCT)”
Yep, this is about right and keeping with the Muraro meta-analysis. Will this be better than the licensed monoclonals? Time to do a randomised, controlled trial with blinded assessors don’t you think?
“Will this be better than the licensed monoclonals? Time to do a randomised, controlled trial with blinded assessors don’t you think?”
No..absolutely not..put away the MAB drugs they don’t work for progressive….Poor..Hauser his rep. is tied to them and now he hedges his bets seemingly runs from them..and embraces them “they will stop pms you just have to treat early” w/Rituximab…no Ocrevus…no Ofatumumab…yeah that’s it.
But the fact remains they did nothing to help his “VIP” patient and yes in another write-up that’s how they referred to him…who went from EDSS 3.5 at time of rituximab to edss 7+ So you have to treat before edss 3..or 2..or 1…how about in utero..?
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5221476/bin/ACN3-4-46-g001.jpg
RE: ” MAB drugs they don’t work for progressive..”
Ocrelizumab is licensed for PPMS.
😉
Lymphocyte reconstitution following autologous stem cell transplantation for progressive MS
Neurological function remained stable in the majority of patients.
Progression-free survival was 69% at three years.
Lymphocyte reconstitution following autologous stem cell transplantation for progressive MS
Autologous hematopoietic stem cell transplantation in relapsing-remitting multiple sclerosis: comparison with secondary progressive multiple sclerosis
https://www.ncbi.nlm.nih.gov/pubmed/28396953
To those on here claiming that there are very few HSCT activists hollering that the treatment is a cure, I have to call BS. There is a large online contingent that have been using the slogan “no chemo, no cure” for years now. Clearly, this implies that HSCT is a cure.
The amount of misinformation I see across online (mostly Facebook) MS treatment info and support groups is astounding and, frankly, frightening. I’ve found that trying to combat this misinformation with some scientific reasoning backed up by fact only serves to make one want to stick their head in a toilet and flush. You can’t change anybody’s mind on these things, and only receive a tremendous grief for your efforts. Same goes for arguing politics online. Better off spending your time smashing yourself in the groin with a hammer…
As a long term PPMS patient (almost 17 years – disease never considered “active”), I do wish that HSCT had been more widely available back when I was first diagnosed and barely disabled. Knowing what I know now, I probably would’ve gone for the treatment with the full knowledge that it probably only had a 33% or so chance of stopping or slowing down my progression. Back then, though, HSCT for MS was in its relative infancy, and the mortality rate was about 1 in 10. Some HSCT researchers at the time were still using full-body radiation to destroy the immune system. Yikes!
There is indeed very little reliable trial evidence of HSCT being effective in non-active progressive ms. Dr. Federenko of Moscow published a paper several years ago which claimed such results, but it was one of the singularly worst medical papers I’ve ever read, and I read a lot of them. The paper was rife with egregious contradictions within itself (which were even acknowledged by the authors in the body of the text), stated outright that there was almost no data on the trial subjects’ pretreatment disease history and very little by way of long-term follow-up. It also stated that due to these lapses, the paper shouldn’t be used as a comparator to other studies. Holy moly, then why even publish?
That said, some of the anecdotal evidence for HSCT being effective for some progressive MSers is compelling. Sober minded folks who have seen a cessation of progression over five years or more are out there, and their accounts very believable. I generally discount those who claim their disease has been halted after having had the treatment less than three years prior, as the progression of progressive ms is quite difficult to gauge even by the patient themselves. I myself have been predicting that I would be bedbound in one year for the last six or seven years. Barring any sort of miraculous intervention, I fear I will soon be right, but the difficulty predicting rate of progression in those with PPMS has been the downfall of quite a few progressive MS trials, in which the placebo group progressed much more slowly than researchers expected.
In regards to my personal situation, at this point my disease has progressed so far and I have so many comorbidities that I truly believe HSCT would kill me. As does my neurologist, who isn’t a fervent anti-HSCT neuro, though I do know that breed is quite common.
Bottom line, as a well-informed MS patient who has been following the HSCT story for almost two decades, the treatment would be my first choice if I were an active relapsing remitting patient, as I feel it would give me the best chance at prolonged and complete remission. That said, it should be stressed that the treatment is no picnic to go through. This fact seems to be all too often glossed over. I’ve known many patients who have gone through the treatment and suffered mightily physically and psychologically in the year following. The chemo used for immune system ablation affects many body systems, and the aftereffects can, for some, be quite hard to get through…
As for progressive ms, if I were newly diagnosed with active disease, I think HSCT would be a relative no-brainer, albeit with the above caveats. The pharmaceutical alternatives simply have too many questions in regard to efficacy and long-term side effects as compared to the more robust results seen in HSCT. For those with inactive progressive disease, though, there’s a lot to consider. As stated previously, had the state of HSCT been where it is today when I was first diagnosed I personally think I would have gone for it, although that decision might not be right for everybody.
BTW, I often wonder if HSCT works not because of its immune reconstitution action per se, but because by wiping out the immune system it also clears the body of Epstein-Barr Virus? And, do those with HSCT who reactivate do so because they have been reinfected with EBV and their genetic predisposition for MS again kicks into action? Seems to make sense to me, but perhaps too simplistic an approach…
Just to clarify the “no chemo no cure” phrase, which has been and is used in HSCT circles quite a lot. For some people, HSCT IS a cure – you can’t really say that it isn’t. Long term remission is surely just that? We know of people 5, 10, 20 years post-HSCT who are still in remission (“No chemo no remission” doesn’t have quite the same ring to it, does it?”). If you are in remission from cancer for 5 years plus, some doctors will say you are ‘cured’.
The real point of that saying isn’t to suggest that everyone who has HSCT will be “cured”, it is to differentiate HSCT from so called ‘stem cell treatments / therapies’ which have no evidence to support them and no real chance of a “cure” or long term remission.
And let’s be honest – a cure is fairly subjective? I know people who feel they are “cured” by virtue of the fact they haven’t progressed in ten years, when they were progressing rapidly prior to HSCT. Isn’t it up to them if that’s the label they feel fits? In some cases, they have lingering damage, but it isn’t getting any worse – the ‘war wounds’ of MS. People in remission from cancer often carry their own scars and lingering damage.
So no, “no chemo, no cure” doesn’t mean “HSCT is a magic wand” – it means that stem cells without chemo cannot offer the same chance for a long term halting of progression (remission).
Your bias is showing, but regardless I am glad your husband is doing well. You somehow managed to miss all of the well articulated points in the post you responded to which is unfortunate. I think you mean well, are relieved that your husband is doing well and want others to have the same opportunity even if your efforts are a bit misplaced. Rest assured that the neuros and neuro-immunologists here also mean well and are doing it in an informed way. Their efforts are roughly in line with yours even though you don’t seem to see it that way and are derogatory to them. Best of luck that your husband stays in remission. I have known a few people that got 5 or 10 years out of it but went back to progression, let’s hope he isn’t one of those.
Hi, good point on EBV that I’m also considering. As stated I had HSCT in 2014 and relapsed in 2018 (while back in 90’s I had a mononucleosis). 2 years after HSCT I have caught a disease manifested by prolonged coughing. I have checked my EBV antibodies and found that I have quite low IgM and high IgG. So it seems that it wasn’t EBV again? I’m waiting now for the genetics tests results to check VDR gene polymorphism (triggered by EBV) and other possible genetic factors.
Finally some reasoned sense to the debate. Thank you.
I sence a bias over proving your “smouldering MS” theory and you try to fit reality in it. Common practice in science.
Re: “smouldering MS theory ”
It is not a theory but an adjective to describe disease worsening in the absence of relapses and focal MRI activity. The other adjective is PIRA.
I read this blog post yesterday and wanted to gather my thoughts before responding.
Firstly – a little about me – I’m 54, diagnosed with MS 2 years ago after 5 years of symptoms. I feel totally let down by my GP and neuro, who initially told me I was imagining my symptoms, then diagnosed me with “benign MS” then RRMS and I now find myself at EDSS 6 (according to my neuro …I think I’m nearer a 5) in a very short space of time. There is now discussion about whether I’m SPMS.
Every MRI shows new brain lesions.
I don’t want to get any worse but no one here is offering me anything ( other than Rebif or Copaxone). I feel I’ve been written off.
I am a member of all the online HSCT groups and have never seen anyone stating HSCT is a “cure” although I am aware of the “no chemo, no cure” mantra. This is used in response to those mentioning “stem cell therapy” without chemo. I see that it could be misleading.
The problem I have as an MS patient is that there is nothing available to me through my current doctors and no sources of helpful information other than listening to the advice and experience of other MSers.
I need to do something to try to stop my MS; I can’t just sit here waiting to get worse. I am booked to go to Russia in March. I know I’m taking a risk. I have no idea how big a risk I’m taking.
I’m sure “chemobrain” is real but how do I find out how big a risk it is for me as an individual? That kind of advice and information is just not available.
There definitely needs to be more research and analysis of HSCT for MS in the UK, but I don’t have time to wait for that to happen.
I was diagnosed with RRMS in late 2017 (low lesion load and no lasting symptoms). I was 33 and otherwise very healthy and very active. I consider myself to have a good brain (MS aside!) and once I got over the shock I set about educating myself on the pros and cons of each of the licensed DMTs – that was hard, mainly because they all come with compromises and none of them is as good as one would hope. It’s also hard because by this point I had no MS symptoms and felt 100% ‘fine’ so choosing to make yourself unwell in the short term to avoid some undetermined long term outcome is a difficult step to take.
I was surprised that there was not more conclusive guidance from my team about what was the ‘right’ DMT to choose – that was left to me. I think I put myself in a position to make an educated decision but I know others who are frankly clueless, whether that be because they are unable or sometimes unwilling to digest the information available. I chose Lemtrada and have now had both rounds and so far so good, no more relapses, no more MRI activity (although who knows whether that might have also been the case had I done nothing). I thought about HSCT but felt that Lemtrada was a better option for me for several reasons (not least because I have no children but plan to start a family shortly).
When I was researching Lemtrada I also spent a lot of time reading about HSCT and joined a HSCT FB group. I was really surprised to find that the HSCT group appear to be incredibly tribal. The tone of the conversation (set by the Admins) is very much ‘them and us’ and they are very derogatory peoples decisions to choose a DMT over HSCT. That is not true in the Lemtrada group I belong to, where people share information freely about various DMTs (and HSCT) in an open and balanced way. I found the dynamics of the HSCT group really unusual and left in the end because I didn’t appreciate what I perceived to be a very unbalanced dialogue. If Lemtrada doesn’t work for me I plan to have HSCT and have discussed this with my neurologist, so I am not ‘anti-HSCT’, quite the opposite. However, I am not interested in being part of the ‘Pro-HSCT’ group because that suggests that one thing is right for everyone and as far as I can tell the evidence doesn’t support that. The people running these HSCT FB groups should consider why (if they think they are running a balanced group which helps individuals make informed decisions) someone like me, found the tone of the conversation so unpalatable. It felt more like a cult that a place to gather information.
I’ll end by saying this (sorry to have gone on for so long) – I do understand (to some extent) why the pro-HSCT people have ended up behaving in the way they have; people get tribal when they think they are under attack or they think they are being persecuted. The medical community has to follow protocol but if I was a person with SP or PP and I knew of other people with the same condition who had benefitted from HSCT, but I was being denied the treatment, then I would be feeling pretty furious about most things. I also think, that the admins on these Forums are good people trying to do the right thing. There seems to be good momentum (not fast enough for people with MS who are deteriorating I understand) behind HSCT in the UK at the moment and hopefully better data will be available in time. I’ll keep looking out for more info here. Thanks for taking the time to write this blog.
I can only speak as an MS patient. Diagnosed RRMS June 2015 with an EDSS of 1.5, by February 2017 diagnosed SPMS with an EDSS of 6.5
Faced with this rapid progression and no other available treatments HSCT was my only shot at stopping the inevitable downward spiral to dependence and death.
The NHS offered me treatment at Kings, but for various reasons, not the least of which was waiting time but also including infection and mortality rates, I went to Moscow instead. Just over 2 years on, I have no further progression. The NHS have abandoned me and there has been no follow up from my neurologist or a haematologist since I got home.
2 years progression free is a win for me already. I don’t claim HSCT as a miracle cure, it isn’t. But it’s the best (and only) available treatment for many people right now. My EDSS is still 6.5 and I never expected anything else.
I really hate the confrontational nature of this post. It serves no useful purpose, other than to ignite squabbles.
It would be more helpful to gather new and current data. Try working with the centres abroad that are talked of so disparagingly. Maybe even leave your comfort zone and attend the symposium in Moscow in November where you can meet with Dr Burt, Prof Snowden and other leading Haematologists to get their up to date facts and figures. If you speak with your favourite “charlatan” face to face you may even learn something.
Great to read this Phoenix …thank you for sharing your experience.
I agree, there was some particularly provocative language used on the original post. It’s a shame as surely we ALL want the same thing? …the best, most effective treatments for MS and improved quality of life for all with the disease.
I agree with Phoenix that at one level the replies to this post have been disconcerting. I’m saddened by the manner of exchange of various views and facts.
Vicky I hope you’ve considered asking to be referred for a second opinion. I did so after my local neuro wanted to stick me on a low level DMT despite three disabling relapses and evidence of still more lesions in under two years. I was referred to Kings and consequently received Lemtrada. That was in 16/17 since which I’m stable with no signs of deterioration and NEDA.
It’s only right that someone like yourself with evidence of disease activity should be considered for the more effective treatments, including HSCT.
Yes, I’ve been referred to Prof Sharrack in Sheffield – had an initial appointment and MRI scan and now having to wait 6 months for a follow up appointment.
I was meant to go to Russia in April this year and delayed in order to pursue this UK option. I’m getting worse all the time so I now regret that delay.
The HSCT militants on social media act as if they are the authorities on treating MS, the same few names, over and over, demanding people do what they did, it’s tiresome. We are all different, and we are allowed our views, even if they don’t match yours. If it worked for you so far, that is great, but that doesn’t make you an authority on what everyone else should do, you are not privvy to everyone else’s circumstances. I have seen some very uncomfortable exchanges on social media where HSCT’ers badger a person to go for HSCT only for the commentator to have to explain their reasons for not being able to. You can voice your opinions and share data that suits you but you have no authority to demand what other pwms should or shouldn’t be doing. Yes, that is how you come across on social media.
Why are you anonymous? I find your comments boring it doesn’t take much to guess who your batting for.
It’s not about sides. That, Helen, is exactly the point.
‘Helen’ (no surname, no profile picture, effectively anonymous) I have ms, I am feeling very unwell, and low, ‘anonymous’ offers a psychological barrier against online bullying.
Your attitude and demeanor mean that you are trying to “win” here and that means you entirely missed the point and like are unfortunately another HSCT zealot from 5e FB group. By the way, you guys have actually turned a few people off of the treatment by taking it to the level of zealot. Really wish you guys would quit and let the actual data speak for itself instead of creating another junk echo chamber.
I agree – it’s either ‘pro’ (good enlightened, one of us) or ‘anti’ (stupid, naive, one of them)
What’s concerning here is the data used stops at 2006. There is a paper with 1951 autoimmune disease patients from 1994 to 2015. That has an accurate portrayal of what happens with progressive MS and hsct. In addition his opinion and the article written that he quoted from because data stops at 2006 aren’t even the protocol is currently used for hsct.
Well, since the long term outcomes are rather important, longer term studies with extension data is also important don’t you think?
Glad I popped by, it’s like the ‘Good Old Days’ but without Leonard Sachs.
Regards as always.
Good ol’ day of Dr Dre, too. This place was like Extinction Rebellion back then!
I think the biggest problem with MS research and treatments is this dogma, that MS is always caused by the same thing.
With almost every treatment report and trial I’ve read so far, whether it’s immunosuppressants, HSCT, antivirals, antibiotics or even vitamin D, there’s always a subset of people who respond well and others who do not. Maybe the cause of the disease isn’t always the same, which would also explain the very different disease progessions.
EBV is causing other reactions than HSV-1, HHV-3, HERVs, chlamydophila pneumoniae, borelliella or whatever…
IMHO, there’s no black swan. There is no best course of treatment and there will be no single cure, because there isn’t a single cause.
MS should be seen as a symptom, like a fever, not like an independent disease.
I had high hopes for HSCT In my desperate search for something to help but am pleased to see it discussed so openly and to read different views.
As there is a strong theory of MS having an infectious cause, possibly EBV I am curious as to why David Wheldon’s ideas have not been taken on board. His treatment idea for his wife involves antibiotics and supplements and appeared successful in her case. It sounds quite logical but what do people think?
Re: “David Wheldon’s ideas have not been taken on board.”
They have and several antibiotic trials have been done and were negative. Interestingly the minocycline trial in CIS was positive but has yet to be taken forward.
There may be a subset of MS patients who benefit from David Wheldon’s antibiotic protocol. One of my closest friends with MS clearly has.
There have been trials with antibiotics, however, I am extremely doubtful if any trials followed Wheldon’s protocol closely for 2 full years using minocycline (or doxycycline), azithromycin, and Tinidazole along with the 10 dietary supplements Wheldon recommended.
Research dollars are not available to study everything needful of study and, naturally, researchers tend to concentrate on specific areas of interest.
MSers have learned to look for benefit outside approved DMTs because of anecdotal cases and/or limited research regarding such things as Wheldon’s antibiotic protocol, alpha lipoic acid (part of Wheldon’s regimen, btw), EGCG, and LDN, for example.
If the truth were known, there are myriads of MSers (IMO) attempting to do something largely on their own which has been advocated at this site… seeking to improve several individual things by 1% or 2% which collectively may add up to a substantial improvement in MS.
PwMS fully understand decades will pass before scientific evidence regarding possibilities easily attainable is available, so, they make their best guess based on limited evidence.
Some, like my good friend, get demonstrably good benefits; many do not… rather like approved DMTs. And, no, we do not have evidence that approved DMTs have a higher probability of benefit and cause less damage compared to the things I mentioned above. Let’s hope so, but scientific comparison is lacking and is not likely to appear any time soon.
That is the world we live in; there is no use lamenting it. An MSer deals with it as well as possible. I much appreciated the person who commented MS may have multiple drivers requiring multiple solutions.
Also, I appreciate this sensible article, and the terrific blog, in general. TY!
One problem with the antibiotics trials I’ve read so far is, that they only used one type of antibiotics. Wheldon’s argument for using three different antibiotics was sound, but hasn’t been replicated in a trial.
The other problem is, that not all bacteria are responding to the same antibiotics. Maybe a subset of MS is caused by bacteria and within this subset there are different bacteria responsible. There’s circumstantial evidence pointing to Clostridium c. perfringens type B, borelliella and chlamydophila pneumoniae. Maybe all three of them – and others – can cause MS.
Same for possible viral or fungal causes. Maybe it’s even all of those things combined in one form or another.
MS is like a cold – it’s the body’s (over)reaction to specific types of (chronic) infectious events, which can be caused by any type of infection.
Better start looking for different infections, start treating for different infections and stop hoping to find ONE cause for MS. After 70 years of research it seems more and more unlikely that there is just one possible cause.
Why do you think HSCT works in this minority of progressive MS though?
In this strange case the patient developed PPMS symptoms after his first allogenic HSCT and was stabilised after his second HSCT (with Alem. conditioning).
https://www.ncbi.nlm.nih.gov/pubmed/30195202?dopt=Abstract&fbclid=IwAR0Q-7JXp9vHRgxP28Tj28vnHZ0LrU7y7V8kwbCU5X4Elkoj0rxr0qQdwT8
We know little dont you think?
Why do you do this Prof G? You know there are desperate MSers out there who are getting more and more disabled because of progressive MS (smouldering MS). These are people like you (mostly in their 40s and 50s) who want to provide for their families / attend their children’s weddings / see some grandchildren / enjoy a retirement.
The failure of mainstream MS research to come up with effective treatments for progressive MS has pushed some people to travel to Mexico or Russia. They know HSCT isn’t a cure, they know the results of HSCT trials is mixed at best. They also know that there is no licenced effective treatment for progressive MS and nothing is on the horizon. Desperate people take desperate measures.
You have stirred up some debate / hot air. I’m not sure your post has helped any MSers. Perhaps it will discourage some from going for HSCT. But without any effective treatments for progressive MS these people will have to watch themselves climb slowly or quickly up the EDSS.
This blog has been going for ten years and still nothing is available to stop disability progression. Sooner or later, the MS research will need to look in the mirror and objectively assess what it has achieved. Until you guys can stop progressive MS / stop patients needing electric wheelchairs / stop young patients going into care homes, MSers will continue to chase any treatment that offers a tiny glimmer of hope.
This. Appreciate the reality check on this crappy disease but sadly my takeaway from the last few weeks of posts as a patient has been: 1) thought I was hitting it hard by “flipping the pyramid “ but apparently am only speeding up the inevitable trip to spms with ocrelizumab. 2) was hopeful that hsct could be available soon but apparently that won’t work either. So as a patient early on in disease with low edss it’s is feeling hopeless that there are any options while I am still in that “early” critical treatment window that has the best chance of long term success.
Ironically this feeling of impending doom and lack of hope would make many patients feel more desperate and more likely to flee the country for something “experimental”. Whether your intent or not prof g my takeaway as a patient has been there are no good options, there won’t be more until I’m past the window where things are most effective, and therefore I am doomed.
I know I’d appreciate a post that offers more hope, especially for those still in that critical early treatment window. For those of us with high functioning still what SHOULD we do other than general wellness which I suspect any reader of this blog is a self selecting educated audience and already careful to do.
The most effective. And only treatment which stops MS in its tracks including smouldering MS. With brain atrophy normalising and only DMT that is shown Confimed disability improvement. Don’t be fooled by the b cell brograde. Ocrelizumab puts out the camp fire but leaves the logs smouldering. HSCT is too risky and God forbid you could be the 1 % that loses his life. Take Alemtuzumab and forget about MS for next 10 years at least.
But I want MORE than 10 years!
10 years is the data from phase 2 to approval to know. No data at present after 10 years. But its effect likely to continue. Until Cause of MS is discovered the immune may learn again to attack mylin.
I just want to clarify to readers that at Barts-MS we do offer HSCT to our patients, including patients with progressive or more advanced MS. However, to be eligible for HSCT under NHS guidelines you have to have active disease. So contrary to what a lot of commentators are implying we do offer HSCT; we consider another option amongst a range of DMTs.
Why are you using data from 1998 to 2006 Ms patients? The correct article that includes 1951 patients from 1994 to 2015 (written 2017) is ncbi.nlm.nih.gov/pmc/articles/PMC5745133. Evolution, trends, outcomes, and economics of hematopoietic stem cell transplantation in severe autoimmune diseases. You’re comparing data for hsct protocols that aren’t even done anymore. Bert has done less than 30 progressive MS patients. There are multiple peer review clinical trials that show what you’re stating is actually what’s false.
Because you can’t have long term data on methods that haven’t been used long term. It has not changed that much, the core components are still there and the data still caries. It is important to compare long term efficacy. If they complained short term there would be no evidence of what endures and what doesn’t. They also need as large a sampling size as possible to be counted as valid.
You’re comparing apples and oranges! Non Myelo v Myelo for one thing.
There is more recent, long term data from Russia which includes many more progressive patients than the data presented here.
конфликт интересов 🙂
No conflict of interest. AA Maximov is a state hospital that treats Russian patients as well as paying patients from overseas. You can’t just dismiss the data on the basis that it doesn’t say what you want it to say.
If you want to talk about real conflicts of interest, what about the fact over 90% of doctors in the USA tend to be on the payroll one way or another of the big pharmaceutical companies? Or how about the conflicts of interest between the MS Society and pharmaceutical companies? Or what about the UK Doctors involved in assessing which drugs should be prescribed to NHS patients who are receiving up to £100,000 per year from pharmaceutical companies?
They’re all fairly substantial conflicts of interest, wouldn’t you say?
Ah, good old whataboutery, wins every argument.
And that comment is akin to saying “You can prove anything with facts though.” isn’t it?
Is it? I prefer thetu quoque fallacy.
Well, not really, because I’d already opened my reply with an answer to your comment that the Russian Data was a conflict of interest – that was my response. I don’t believe there is a conflict of interest at AA Maximov.
The additional comments about conflict of interest were intended more as an attempt to widen the debate and to get you to think more broadly about that generally in this sphere, rather than to ‘win the argument’.
I see where you’re coming from though.
Attempt to widen the debate or muddy the waters? I’ll let the jury decide 🙂
As you can imagine I’m well aware of the multiple COIs in MS. I also believe in HSCT as a very good option for those for whom it is appropriate. I am not in favour however of those travelling abroad for HSCT being sold a false prospectus, aided and abetted by Facebook groups making unsubstantiated claims and with the only potential long-term outcome being anorexia of the wallet.
We’re just going to have to agree to differ. As an HSCT focused charity, AIMS is in touch with patients from Mexico and Russia on a daily basis – long term and short term patients.
Thousands have been treated now (most of them progressive patients) and a large proportion of them did begin their journey in the Facebook groups, you’re right. But why was that? Largely because of neurologists telling them “You WILL come home in a box”, “It has a 30% mortality rate” “It’s akin to witchcraft” “It’s only suitable if you have six months to live” “can you spell haematopoietic for me?” and many, many similar variations on the same theme. All of the above are genuine quotes from neurologists! Can you begin to see why people are dubious?
These people were looking for answers from people who had actually been through the procedure, as opposed to the anger (yes, anger) they received at the hands of their neurologists for even daring to THINK of questioning their judgement.
Nobody holds a gun to anyone’s head in the HSCT forums, we share information – and it’s usually a LOT more accurate that the information they’ve received up to the point that they find us.
Our groups are about support, autonomy and helping people. I personally know several people whose plan was to go to dignitas before they found HSCT. They are grateful they found our groups and were able to self-advocate. HSCT hasn’t been a magic wand for them, but they haven’t progressed and are glad they had HSCT. The number one thing we hear from HSCT veterans is that their only regret is that they didn’t have it sooner.
You cannot tell someone how they should live their life. There is nobody who has as much of a vested interest in your health and your life as you do. As far as ‘anorexia of the wallet’, yes, HSCT is expensive and it is hard for ordinary people to raise that kind of money. But you cannot put a price on halting progression – it’s worth trying. There is no alternative for most of these people! There certainly was no alternative for my husband – that was made very clear.
There are over 30,000 people in the various HSCT Facebook groups. Maybe a tenth of that number have now had HSCT for MS in the last 20 years. We have many progressive MS patients in our groups who have had HSCT 5-20 years ago and haven’t progressed (many of them form part of the Russian data you’ve chosen to disregard).
There are around 2,000 members in the HSCT veterans group, but just 84 people in the non-responders group, which is widely publicised in the other groups to offer support to those who may need it. I’m sure you’ll dismiss that fact too, but there it is.
You can call us zealots, evangelists, militants – whatever you like. The fact remains that there are many, many people in remission from their progressive MS because of HSCT. There are others who wouldn’t be with us at all today because they had planned to end their lives rather than continue – if they’d listened to the advice from their neurologists, then they’d have ended their lives – that’s the stark reality.
If HSCT saves even one life in such circumstances then that’s a good thing, and if we have to put up with a bit of name-calling when all we’re doing is supporting people, then so be it. Do your worst.
Hey Alison,
Could you please provide a link for the more recent long term data so we can at least review it and make up our own mind regarding whether or not it is any good.
The paper you referred to from 2015 is far from first class evidence and the cohort was in fact quite young with early disease(on average).
Would love to see convincing evidence to support your claims of efficacy in PPMS.
If the data from the Ottowa trials is valid (which ended in 2006 and included 24 in the cohort, all under 45, no PPMS patients) why are you questioning the Russian data, which relates to a cohort of 99 with a mean age of 35 and included 56 patients with PPMS?
Sorry – I’m just a little confused about why you seem to think that one set of data which didn’t include any progressive patients and used myelo HSCT somehow provides more evidence in terms of the outcomes of HSCT for PPMS than a larger study with a similar age group that actually included PPMS patients (more than half of the cohort, in fact)?
Can you enlighten me?
Because neither conclusively point to HSCT being effective in progressive MS!
Ohhhh. Except for the one that does, you mean?
The Ottowa one didn’t measure PPMS outcomes at all. The Russian one and the outcomes were positive. 75% of the PPMS patients had no progression at 4+ years. Most PPMS patients I know would give their right arm for a 75% chance of 4 years of being progression free – they are scared of where they’ll be in twelve months, never mind 4+ years.
That paper was dated 2015 (nearly a decade on from the Ottowa research in the original post) perhaps you could follow up with Dr Federenko at AA Maximov for a 2019 update if you feel that this data isn’t of any merit?
But you won’t, will you?
Sorry Alison,
This isn’t a fight. It is a discussion. The 2015 paper has a groups of ”progressive” patients of young age with reasonably short disease duration, and no clear way or defining ”progressive” disease.
As has been discussed, the idea of MS being different diseases is not overly accurate and can be roughly equated to time since diagnosis.
We all want HSCT to be a safe panacea. Don’t worry. I cannot speak for the other skeptical people out there, but I would like to see more convincing evidence regarding efficacy and safety in more advanced disease(the 2015 paper is not great, sorry, but the study is poorly controlled, the groups are poorly defined, the number of patients is too low to draw major conclusions from, the study is observational the list goes on).
Whether or not you like it, the Moscow and Mexican groups have not produced evidence that strong enough to convince me anyway.
I will leave it there.
Considering the disease duration(instead of ”progressive vs relapsing”) the Russian cohort is actually that of patients with relatively early disease.
But how is that even relevant when your whole premise is “HSCT doesn’t work for progressive MS”?
My husband was comparatively early in his disease when he had HSCT. He was diagnosed at 40 and 4 years later he was SPMS and EDSS 6.5. He had no active inflammation and no new T2 lesions – his disease has been halted according to Dr Kazmi. I realise it’s inconvenient that he slipped through the net!
Explain to me the relevance of disease duration when the patients are still progressive MS (PP and SP) with no active inflammation – don’t forget that that’s why most of them are forced to go overseas, because the UK criteria rely heavily on active or new T2 lesions. Progressive patients are less likely to show that, no matter how early they are in the disease duration.
Some people with SPMS have active SPMS and are simply failing to recover from multiple focal lesions, which can be microscopic (below the detection level of the MRI scanner). One of our patients went into the SPMS siponimod trial with an EDSS of 6.0, naive to previous DMTs, an MRI with no new T2 lesions or Gd-enhancing lesions and within 12 months her EDSS recovered from 6.0 tp 3.5. There is more to having SPMS than a diagnostic label of SPMS. I would be interested to know what your husband’s CSF neurofilament levels were. I am sure they would have been sky high, i.e. he had a lot of ongoing inflammation.
A lumbar puncture wasn’t done prior to his HSCT, only at diagnosis, and I hear what you’re saying, but that surely can’t apply to all the progressive patients who have travelled abroad?
Or – if it can – is it time to change the UK acceptance criteria to include a lumbar puncture to establish CSF neurofilament levels?
From what you’re saying, it’s certainly possible that my husband had a lot of hidden inflammation (and I have always said that I believe he did). In fact, his neurologist and haematologist were both surprised that the MRI showed no inflammation, given their clinical observations. He sneaked in really, although he did not fit the criteria.
However, he would not meet the criteria today, which is a lot more strict. It seems that patients who could respond well to HSCT may well be being missed. Would you agree?
177 comments
And counting 🙂
The “colective cyborg” need trafic? ,easy just write Hsct 🙂
Come on, lets bump it up to 200
🙂
This is certainly a polarising post given the emotional comments below. I’m very skeptical of the HSCT proponents who fail to take a balanced view of the risk / benefit profile of HSCT in progressive disease. If you read Prof G’s posts concerning HSCT, he has consistently argued that it should be available as first line treatment for those with active inflammatory disease. Until solid, peer reviewed evidence emerges for HSCT’s utility in progressive disease, I’d approach it with caution. It’s not the panacea certain people believe it to be. This is evident by the published data.
It is unfortunate that there is so much finger pointing and finger wagging here in reply to the original post, yet not much actual careful listening [er, reading] and consideration.
Without the benefit of a multi-year advanced education [read: university] in science—specifically biological science—it is nearly impossible to have a good working knowledge of the concepts and factors involved in the subject of this conversation, that seems to have degenerated into a lot of virtual yelling and exasperation. Research is much more than reading science papers—and unfortunately a lot of that usually ends up being in the form of abstracts and Wikipedia articles, which is light years away from being somewhat close to enough. The passion is understandable, as multiple sclerosis is a horrific disease and answers are few. But the conversation is going in circles, becoming more and more combative and divisive… almost like a war zone. People on here have strong opinions about being able to be allowed access to anything that might help them, even if the chance of helping is infinitesimal. Understood. But those same people are not listening that no one is arguing about that. The first point of the original post is a fact: “I post to manage expectations and counteract fake news. There is a group of pro-HSCTers going around and saying HSCT is a cure for MS even in MSers with more advanced disease, i.e. it halts and reverses their disability. This is simply not correct and we have no published, peer-reviewed, data to support their position.” That is a fact… there is no published, peer reviewed data to support that assertion. Are there papers that show some favorable findings? Yes, but with a note, or an asterisk if you will. Are there anecdotal reports of favorable outcomes? Yes, but those should definitely have an asterisk next to them. And the notes should be that results are speculative and not proven through peer reviewed research with widely reproducible results, as well as being safe and efficacious. That last sentence being the most important. The scientists and doctors, without ulterior motives, are saying that this procedure is unproven and unpredictable for the MS public at large, and many times more risky for people with advanced MS, especially people who’ve had MS for many years. It is actually well known that many of the DMT drugs won’t do much for people in the progressive phase of MS, if at all. The reason is multifactorial, but in large part because you can’t use a modifying therapy when there’s nothing to modify. Most all of the drugs combat the immune system attacking and the resultant inflammatory damage. At some point in many if not most people the attacks cease, or become subdued, and the nerves just degrade and disintegrate. There’s nothing to affect at that point with the current drugs, and HSCT would just be a risk to POSSIBLY accomplish little to nothing. This arguing about published papers showing favorable results, and experts who know much more, as well as hematologists vs neurologists is just ridiculous. The original post is by someone who devotes their time to helping people better understand aspects of this awful disease, and help navigate the bad information and pitfalls inherent in our constantly plugged into the information superhighway world. That effort should be applauded, not bombarded like angry villagers at Dr Frankenstein’s door. A few people who regularly post here to be informative and share ideas do so respectfully and seem to be open to all comers, but that also doesn’t mean there will be agreement or consensus. Please be respectful as well, and please follow your own advice to do more research. This is in no way meant to be facetious or condescending, but start with the basics and make sure to give plenty of time to deep diving into the research—there’s always much more to learn. And never stop asking questions.
Could not have said it better!
Big round of applause👏👏👏
How utterly patronising to suggest that the research of someone with MS could only amount to the reading of abstracts and Wikipedia pages – I think that really demonstrates how little you know and what a very low opinion you have of us. Astonishing.
What a shame that you felt the need to come back to this post to assert your superiority in this way.
I think this is the point where we say “we’ll have to agree to differ”, but while we’re on the subject – perhaps you could share your views on the importance of research into HSCT with some of the very many neurologists in the UK who seem so reluctant to even educate themselves in the most basic way on the topic.
It seems to me that this is a case of “I really must have the last word!” – be my guest. But do be mindful that there are many of us “HSCTers” who are working with similarly altruistic reasons (unpaid) to the same ends.
We will send your regards to Dr Federenko (whose research you’ve dismissed) at the International HSCT conference in Moscow at the end of this month. And Dr Burt. And Dr Saccardi. And Dr Burman…and the many other key people in the HSCT world who evidently have some respect for the Russian data for them to attend and speak at such an event.
My irony meter has just exploded 🙂
Really? You don’t think that’s what that was, revisiting the post 2 weeks after the dust had apparently settled?
Pure provocation. Really not a scab that needed to be picked…
Pure provocation?
Now my hyperbole meter has gone too 😉
You’re really spoiling me with the literary devices today!
I have the Ferrero Rocher to hand too. 🙂
The amount of weight put behind the 2015 paper mentioned above does hint towards HSCTers either not reading the paper or not understanding it.
The strongest evidence(MIST study) excludes progressive/advanced disease.
200 Almost there
🙂
Yes, SPMS and PPMS with active disease. We don’t treat pwMS who have inactive disease. We differ to most groups in that we look hard for active disease including doing LPs and checking for raised CSF NFL levels.
Prof G, thanks for the hard work you have put into these studies. I looked at HSCT years ago and was put off by the cost and lack of long term studies. Your thoughtful work is helping lots of ms patients and their physicians make informed decisions about the complex array of treatments. Kudos!
Hsct can stabilize MS my wife had letter and more to prove it from her Neuro 2yrs post.
https://neuro-sens.com/hsct-vs-drug-in-rrms-head-to-head-study/
https://n.neurology.org/content/90/15_Supplement/S36.004