Barts-MS rose-tinted-odometer 0/★
I am often asked why given the extraordinary efficacy of HSCT in early RRMS, but not advanced MS, why I don’t refer more of my patients for HSCT early on in the course of their disease. There are several reasons these are the main ones.
Firstly, to be eligible for HSCT under our London guidelines patients have to fail at least two DMTs one of which has to be a high-efficacy DMT (fingolimod, cladribine, natalizumab, ocrelizumab and alemtuzumab).
Secondly, the infertility risk is too high. It is quoted to be in the order of 40-45% and most women and men want to keep their ovaries and testes in a functional state. Although the process of sperm banking and oocyte or egg harvesting, and storage, are routine it takes time to set it up and get it done. In my experience, the harvesting and storage delays treatment by several months. This delay is not ideal for someone with highly active MS. In addition, the costs of sperm and egg banking are not always covered by the NHS. Funding for this is a post-code lottery and depends on where you live.
Thirdly, the mortality that is quoted for HSCT often puts people off. The London team talk about a mortality risk of up to 2%. In reality, the real risk is closer to 0.5%, i.e. a 1 in 200 risk of dying from the procedure. For some people, this risk is unacceptably high.
What I haven’t really discussed with my patients is the secondary cancer risk post-HSCT. As HSCT involves receiving the chemotherapy compound cyclophosphamide the secondary cancer risk can’t be ignored. Cyclophosphamide is an alkylating agent that cross-links DNA. It is a mutagen and is known to cause cancer. Its metabolites are excreted in the urine and increase the risk of bladder cancer rate massively. Although we use mesna to protect the bladder against acute cyclophosphamide toxicity it does not prevent the cancer risk. The bladder risk is particularly high in MS if you have bladder dysfunction with incomplete emptying and/or need to use a catheter.
There is, however, one small French study of 354 people with progressive MS who were treated with cyclophosphamide that looked at cancer risk post-cyclophosphamide. The cumulative incidence of cancer after cyclophosphamide was 3.1% at 5 years and 5.9% at 8 years, which is described as being similar to the expected background rate.
At present we don’t have figures for how high the cancer risk is post-HSCT in pwMS. I suspect the cancer risk is likely to be in the order of 3-5x higher than the background rate. This figure is based on studies in other disease areas. Is this important? Yes, I have many female patients saying no to ocrelizumab on the basis of a possible increased risk of breast cancer with ocrelizumab. Surely, the HSCT units should be auditing their data and providing us with a cancer risk based on the longterm follow-up of their patients? If they want to convince the wider MS community to adopt HSCT and potentially use it as a first-line DMT then we need to know the longterm risks associated with its use.
van den Brand et al. Cancer Risk After Cyclophosphamide Treatment in Idiopathic Membranous Nephropathy. Clin J Am Soc Nephrol, 9 (6), 1066-73 2014 Jun 6.
Background and objectives: Cyclophosphamide treatment improves renal survival in patients with idiopathic membranous nephropathy. However, use of cyclophosphamide is associated with cancer. The incidence of malignancies in patients with idiopathic membranous nephropathy was evaluated, and the cancer risk associated with cyclophosphamide use was estimated.
Design, setting, participants, & measurements: Patients who attended the clinic were included prospectively from 1995 on. A crude incidence ratio for the occurrence of malignancy was calculated. Incidence ratios were subsequently standardized to potential confounders. Latency between cyclophosphamide therapy and the occurrence of cancer was estimated by stratifying for time since the start of treatment. Finally, Poisson regression was used to obtain a multiple adjusted incidence ratio and investigate the dose-response relationship between cyclophosphamide and cancer.
Results: Data were available for 272 patients; the mean age was 51 years, and 70% of the patients were men. Median follow-up was 6.0 years (interquartile range=3.6-9.5), and 127 patients were treated with cyclophosphamide. Cancer incidence was 21.2 per 1000 person-years in treated patients compared with 4.6 per 1000 person-years in patients who did not receive cyclophosphamide, resulting in crude and adjusted incidence ratios of 4.6 (95% confidence interval, 1.5 to 18.8) and 3.2 (95% confidence interval, 1.0 to 9.5), respectively.
Conclusion: Cyclophosphamide therapy in idiopathic membranous nephropathy gives a threefold increase in cancer risk. For the average patient, this finding translates into an increase in annual risk from approximately 0.3% to 1.0%. The increased risk of malignancy must be balanced against the improved renal survival.
Le Bouc et al. No increase in cancer incidence detected after cyclophosphamide in a French cohort of patients with progressive multiple sclerosis. Mult Scler. 2012 Jan;18(1):55-63.
BACKGROUND: Cyclophosphamide is still used in progressive forms of multiple sclerosis (MS) in view of its suggested efficacy and safety in the short term. No data exist on its long-term safety in MS, particularly on the risk of malignancy.
OBJECTIVE: The objective of this study was to evaluate cancer incidence in MS after cyclophosphamide treatment.
METHODS: We performed a historical prospective study in a cohort of MS patients treated with cyclophosphamide. We collected demographic data and medical history from medical databases and patient interviews. Reported cancers were histologically confirmed. Cancer incidence was compared with the incidence in the general population by estimating standardized incidence ratios (SIRs).
RESULTS: We included 354 patients, with a median follow-up of 5 years (range 2-15) after cyclophosphamide treatment. Fifteen patients developed a solid cancer, which occurred at a median of 3 years (range 0.5-14) after cyclophosphamide introduction. The cumulative incidence of cancer after cyclophosphamide was 3.1% at 5 years and 5.9% at 8 years. We found no increase in cancer incidence after cyclophosphamide treatment in men (SIR = 0.83, 95% confidence interval [CI] 0.30-1.82), women (SIR = 0.99, 95% CI 0.43-1.95), or men and women combined (SIR = 0.92, 95% CI 0.50-1.54).
CONCLUSION: We found no evidence of an increased risk of cancer associated with cyclophosphamide treatment in MS patients.
CoI: multiple
Isn’t risk monitoring a job for the EBMT?
Why is it down to 1 physician in 1 hospital and 1 EU country to deal with challenges of this magnitude?
And ps, I raised this point back in March:
“-HSCT has a significantly higher risk of mid-term and long term secondary malignancy compared to alemtuzumab. No plateau was seen to cap this risk neither.”
source TONY FONDA March 12, 2019 at 8:48 am: https://multiple-sclerosis-research.org/2019/03/1st-line-hsct/
Yes, the EBMT does collect data on secondary malignancies, but I can’t find figures for patients with MS receiving autologous HSCT. The data must be available.
Couldn’t find it back in March neither (as you know, I was seriously exploring HSCT at the time)
On a similar note, have you found any data of gene expression modulation of patients on natalizumab for the very long term (10ys+)?
https://multiple-sclerosis-research.org/2019/10/11451/
Autologous haematopoietic stem cell transplantation and other
cellular therapy in multiple sclerosis and immune-mediated
neurological diseases: updated guidelines and recommendations
from the EBMT Autoimmune Diseases Working Party (ADWP) and
the Joint Accreditation Committee of EBMT and ISCT (JACIE)
Other recognised late effects include secondary
autoimmunity (up to 10%) either de novo or within the
spectrum of the original AD [41, 113–115], endocrinopathy
[33, 41] and late cancers [15, 35]. Concurrent AD is
not infrequent and an appropriate screening (e.g. thyroid
function) at baseline is mandatory. Although data are
limited, the risk of PML appears low, with no current
reports post-aHSCT, including in over 1400 patients treated
for MS in the EBMT registry despite the frequent use of
DMTs prior to transplantation (Table 1). Late effects are
the subject of ongoing EBMT retrospective studies, but in
the meantime, it is important that systematic screening is
undertaken in accordance with current recommendations
for late effects [26, 107].
https://multiple-sclerosis-research.org/2019/10/11451/
Looks like the data gathering is ongoing
However Paolo Muraro as this to say
The analysis of late events included malignant cancers and new onset of autoimmune disease. With regard to malignant cancers, 1.1% (3 of 281) of patients had a myelodysplastic syndrome, a disorder associated with prior treatment with cytotoxic drugs. The other neoplasms observed in this cohort are usually not associated with previous chemotherapy. The incidence of new autoimmune disease was 5.0% (14 of 281), in line with a survey administered by the EBMT25 but considerably lower than after lymphocyte-depleting treatment with alemtuzumab, which approaches a risk of 50%.26
Long-term Outcomes After Autologous Hematopoietic Stem Cell Transplantation for Multiple Sclerosis
https://www.ncbi.nlm.nih.gov/pubmed/28241268
After 10 years Joachim burman as this to say
No patient developed a malignancy
and it is certainly encouraging that no unexpected serious adverse
events occurred during the 10 years of follow‐up.
https://multiple-sclerosis-research.org/2019/07/hsct-is-it-remission-or-is-it-a-cure-for-ms/
I am not sure if there are the necessary numbers to make a call on this, for example, the last study only involved 10 patients.
Take a look at the webinar that Dr Federenko broadcast yesterday evening, Gavin (bearing in mind that he has now been invited to include his data in the EBMT)
He explains REALLY clearly why he treats progressive patients and very deftly gives excellent credence to his reasoning. He takes on the “naysayers” with calm and measured explanations. He also mentions QOL (Quality Of Life) at least 5 times (which is 5 times more that it is generally mentioned by UK Neurologists).
LINK REMOVED
Dr Burt, when I heard him speak, equally gave reasons why not to do progressive MS, Federenko is surely conflicted as a recipient of fee for service. Do Turkeys sell try and sell Christmas?, No but the Supermarkets do.
Dr Burt spoke in Russia too – he said he’d welcome further trials to assess HSCT for progressive MS. He definitely isn’t against that, he’s based his opinions on a mouse model he conducted over 20 years ago.
You can see his presentation, and responses to the Q&A in the AIMS Facebook group (we will shortly upload to our website too).
As far as turkeys voting for Christmas, my husband had successful HSCT for his progressive MS on the NHS. Merry Christmas indeed! 🎄
Yes trials, so this can be done in a systematic way, but he can’t have realistically based any ideas on a progressive mouse model 20 years ago, they didn’t exist then. Therefore he was deluding himself.
There is no question that some elements of progressive MS will respond to HSCT and if it was on the NHS one may be guess there was disease activity, but this is not the point. The manager of Leeds United may say they are great at football, but they are still in the Championship.
In my husband’s case – no active lesions and no new T2 lesions – he was one of the early patients in the UK and slipped through the net.
Dr Burt stated that he based his decision not to treat progressive MS on the mouse trials – do watch the videos – they’re a bit of an eye opener! The group is public so you don’t need to be a Facebook member to see them.
This is a slick advertisement for rich foreign patients. I doubt he cares about poor Russians with MS. I believe it is only rich Russians who can afford HSCT.
You couldn’t be more wrong. I’ve met him. And having met many private doctors in the UK I think I’ve become quite astute at telling the difference between someone who does the job because they are genuinely compassionate and those who are in it for the money. Furthermore, the role of consultat haematologist doesn’t pay much in Russia – around the same as teacher in the UK.
Alison does your husband have regular MRIs and cognitive tests? I am interested to know what his annual brain volume loss is and whether or not his cognition is holding up. Progressive MS is much more than what the eye can see.
Yes, he does. He sees his neurologist once a year as well as his check ups with his haematologist. All his symptomatic improvements (and there were over 20 at 12 months) have held. Both neuro and haemo are very happy with him. His EDSS is the same (6.5), but his quality of life has improved enormously.
This is not a webniar it comes across as an advert
Anywhere else in the world, except maybe the US, this would be considered advertising and would be banned. In the UK doctors are not allowed to advertise their services. This is what the GMC says about communicating information:
68
You must be honest and trustworthy in all your communication with patients and colleagues. This means you must make clear the limits of your knowledge and make reasonable checks to make sure any information you give is accurate.
69
When communicating publicly, including speaking to or writing in the media, you must maintain patient confidentiality. You should remember when using social media that communications intended for friends or family may become more widely available.14, 27
70
When advertising your services, you must make sure the information you publish is factual and can be checked, and does not exploit patients’ vulnerability or lack of medical knowledge.
71
You must be honest and trustworthy when writing reports, and when completing or signing forms, reports and other documents.22 You must make sure that any documents you write or sign are not false or misleading.
You must take reasonable steps to check the information is correct.
You must not deliberately leave out relevant information.
Have you actually watched it? I’m not sure that you have from what you’re saying here.
It is a webinar. But then, I think you’d say that whatever the format. You’ve already made up your mind when it comes to Russia.
Yes I started to watch it
When it comes to Russia have I made.up.my mind, no but this doesn’t make.memthink good things.
That’s perfectly OK. The world’s leading HSCT practitioners evidently don’t agree though, as they all presented at the Moscow conference and were very supportive of Dr Federenko. But, you know, each to his own…
Yes each to her own
This is a business. Is it science?
It’s a state hospital.
Would you ask that question of the UK hospitals / practitioners that treat on the NHS and privately?
I’m getting HSCT in Mexico right now at Clinica Ruiz in Monterrey. I am an American. I had a hysterectomy at age 27 for endometriosis, which I believe has some remote connection to MS, so MS took my fertility, but thankfully after I had my children. I was denied DMTs for yrs bc the neurologist was waiting for new lesions, which I believed then that the McDonald’s Protocol was wrong and quite frankly think there is a flaw in the whole diagnosis process of MS when progression is measured by the irreversible damage done, yet the symptoms just ‘managed’ making life unbearable. That first neuro wanted to follow the rules, which I respected at the time. It took ME overcoming the drawbacks of the military medical records system which by human error punched in the computer to ‘retire’ my St Louis records warehouse when in reality, my records with a brain MRI done 20 yrs ago left on the shelf of Fort Bragg, NC. That first Neuro, a Navy dr who I believe he believed he was doing the right thing claimed his office tried to find my records. I was dx’ed when I gave him the MRI. The McDonald’s Criteria for MS dx’ed was updated to allow for DMDs to be RX for pre-MS (like me) AFTER my crisis So, hallelujah, I got Gilenya. But Gilenya☠️my liver with enzymes AST 1800 and ALT 1200 60X normal, triggered chronic pain that led me to medical cannabis, Ocrevus made me very 😷 with Glossopharyngeal Neuralgia that was dismissed for 10 months because Genentech claimed they noted my symptom in their ‘infusion reactions’ but , damaging my 9th cranial nerve. I petitioned Genentech to change their warnings so that neuros wouldn’t dismiss this. IDK if they did. So, in the work up for my Glossopharyngeal Neuralgia, I had to get an, and an MRA to see if the GPN could be fixed with surgery for people who get GPN or TN for non-Ms reasons. I wasn’t a candidate for the surgery. But, that’s when I heard of HSCT for MS and applied for the Chicago trial with Dr. Burt and the nurse called me saying I could get approved if I could get a new MRI done. I quickly asked my neurologist, but he denied me the MRI because I just had an MRA, plus I was fighting off off a stubborn upper respiratory infection (also noted as symptoms for Ocrevus), 11 b2b UTIs which developed into bladder emptying problems and I had to do the humiliating practice of catheterizing which everybody knows makes fighting UTIs even more difficult, AND several other even more embarrassing infections. So, then, Tecfidera got me more lesions, which got me actually excited bc I could then be accepted for Dr Burt’s HSCT trial. Also, the actress Selma Blair has just gotten it done with Burt and now I had the MRI I needed. THAT WAS THE VERY WEEK THE ANNOUNCEMENT HAD BEEN MADE THAT BURTS TRIAL WAS SHUTTING DOWN! I was devastated to say the least and very bitter, because Burt was the only US trial for non-myeloblative HSCT for MS even though it would cost me $150,000 out of pocket. Thankfully I decided to go to Mexico. They are awesome here and I believe better than Burt’s protocol and I believe he knows this and is angry of the medical freedom allowed to Mexico bc they don’t have such strict rules and the corrupt FDA.
You Neuros have no clue about MS, with all due respect…what little I have for the neurology community! You are puppets of the insurance companies and the pharmaceutical companies who line your pockets with cash to incentivize prescriptions for their nonsense drugs (that have worse promise for MS and same risks for cancer and the deadly brain infection PML). My current Neuro who was lukewarm about my coming to Mexico and refused to help me find other clinical trials, gets over $137,000 from pharma EVERY YEAR.
You have no clue what power you have to make things right for MS patients if you relaxed your insistenc e for further proof for HSCT. I am just one victim of the US medical flaws and it sounds like the UK is not much different. It’s confirmed by my new lesions that maybe Ocrelizumab or any of the other mab drugs might work for MS, but consider PLEASE that MS patients have to take these drugs for life, while having NO Quality of life. Confused why insurance companies wouldn’t see it differently because they shell out $100,000 a patient every one of those years. I see why pharma loves it. One of the doctors here at Clinica Ruiz said to me yesterday, “If DMDs were the answer to MS, then why do we need 15 different ones and every pharmaceutical company has their own version?” HSCT is a one time procedure and hopefully I will be in the 80% of patients of STOPPING MY MS rather than at most 65% of only SLOWING MY MS with the meds!
You deny patients and claim it’s for safety and rely on proof the pharma meds work by absence of lesions! How does that prove they are working when we still don’t know what causes MS, but it’s not the lesions and you can’t take those lesions away when you see them!
You Neuros don’t need more data from HSCT researchers, it’s right in front of your face and you don’t even care enough to speak for your suffering patients.
It’s why I will continue to see a hematologist after my HSCT here for follow up at University of Virginia- Dr. Kindwall-Keller who wants to do HSCT for MS but insurance won’t cover it and she’d have to charge me $150,000 and I’d be her first ever MS patient. There are hematologists like her who have been doing HSCT for cancer and have won accolades for their work. She can’t do it because of the neurologist community stick in the muds! I hope to help her.
You neurologists need to stop acting like the gods you think you and admit you need to rethink things about MS! Yoda said it best, “Fear leads to…Suffering” But who cares, there’s only 400,000 MS patients in the U.S. Oh wait! That changed. You guys never had us counted right You admit and now there are 1 million. That’s a start…start looking in the mirror, because the problem is Neuros with HSCT not the researchers!
Now you have got this off your chest….what has this got to do with us?
Best wishes
Do you think, maybe, if you showed some compassion that it might contribute to changing the perception of people who feel they need to make a post like this? Just a thought.
To be honest no. We are not a soap box. There are plenty of sites that are soap boxes.
Do I think I can change your opinion of HSCT?
Many people have a low opinon of neurologists, I certainly have a low opinion of some neurologists and frequently say so and therefore I can empathise with the post. However it was a rant at “You neurologists”. I am not a neurologist and therefore the rant was not directed at me, but rant it was. The neurologists being questioned don’t have a right of reply.
Many websites are staffed by doormats, who are happy to say every thing is wonderful and we are all made out of star dust. I made a decision not to be like that, and no doubt suffer the consequences, and so our posts are not all this science is wonderful. Likewise, I decided at the outset not to be a doormat and if you throw stones I may bite. After all….you say I am an a lapdog:-).
However, I accept that we are not always right and that people can have different views and there are welcome as long as they are presented in a constructive way, then this is good for debate. However do it in no-constructive way, we as a community should not accept it.
However, we are not a punching bag. ProfG won’t say anything and will take it, but someone needs to say something
A good debate doesn’t rely on rudeness though, does it? It takes in the other side’s point of view and uses evidence to rebut and demonstrate why they’re wrong. That’s the best way to bring someone round to your thinking.
Condescension will never persuade someone that they’ve got it wrong and it isn’t the mark of a good debate – to me it’s akin to when someone starts swearing when they’re clearly losing the argument.
You don’t need to be a doormat, but you don’t need to be so rude either. Sometimes it’s actually very funny, but mostly it’s a bit grating.
And the neurologists DO have a right of reply – of course they do. This is a public platform.
Do you realky think the Neurologists involved in the rant read the blog?….If they do they are not going to comment.
Sorry if I am grating, some may throw the comment back. 🙁
Who knows? Our neurologist couldn’t even spell ‘haematopoietic’, so you make a good point if you’re suggesting that there may be others out there who can’t read. Stranger things have happened.
No apology necessary – it’s the season of goodwill to all men (and mice).
I think you misunderstand the situation in the UK and in London. We are allowed to treat pwMS using HSCT and the NHS will cover the costs. We know that HSCT is very effective, but we don’t have a clear understanding of its relative safety, which is why the NHS is funding a new HSCT vs. Ocrelizumab/Alemtuzumab. Unfortunately, this trial is not being done in very early MS, i.e. 1st-line, but in DMT failures.
We don’t consider HSCT to be any different to other immune reconstitution therapies, i.e. it is working in the same way only it is likely to be more effective. Based on this argument HSCT is just another DMT; it works in most people with early MS, but like all DMTs its impact on smouldering MS is limited.
I think you can make such broad generalisations about neurologists; we aren’t all the same. Similarly, the idea that there is some conspiracy between neurologists and Pharma in highly unlikely. I agree that the Pharma charge too much for MS DMTs, etc. but there really is no alternative to Big Pharma when it comes to drug development.
Finally, we at Barts-MS are trying to address the unaffordability of MS treatments with our Affordable Essential DMT list. Interestingly HSCT is on that list as an option. I, therefore, have to agree with the MD when he asked the question: “What has your dilemma got to do with us?” and this post?
All I am asking for is data on the secondary malignancy risk that arises as a result of having your MS treated with HSCT? When you signed the consent form for HSCT did it cover the secondary malignancy risk?
I don’t think she does misunderstand the situation in the UK and England – it’s not that different from the situation she’s encountered in the USA.
1. Around 0.1% of the total UK MS population has been treated with HSCT in the UK
2. All neurologists may not be the same, but there is absolutely a trend that suggests a very high proportion of them are unsupportive and limited in their understanding of HSCT.
Your response is more understanding than Mousedoctor’s, but you are missing the point somewhat if you can ask “what does this have to do with us / this post” without a trace of irony! Come on, Gavin – really?
I am very glad that no neurologist I have seen for my PPMS has even suggested that neurotoxic HSCT might be a good idea for me. And I am grateful of the level headed approach by the Barts team on this blog. Too many people with MS become entrenched in their views and quite aggressive in defence of their standpoints. Which often amount to extrapolation of n=1.
And you’re perfectly entitled to your opinion! But there are many people who would appreciate the choice of HSCT v rapid deterioration. My husband chose the latter (and was treated on the NHS). After a period of very rapid decline he has had no progression AT ALL in the last 3.5 years, and many symptomatic improvements. We are certain that without it he would be in a wheelchair or even bedridden by now.
You’re entitled to your choice – and so is everyone else.
Exactly Alison. Everyone is entitled to their opinion and assessment of anecdotal reports and scientific evidence. Perhaps you should remember that yourself, instead of attempting to browbeat everyone into sharing your own perspectives.
I don’t attempt to browbeat anyone – I simply present the other side of the argument, ‘Anonymous’.
HSCT is an incredibly personal decision and you’ll never find me telling anyone this is the route they should take. It’s just a shame that the same sense of ‘freedom of choice’ isn’t shared by many neurologists.
Just a thought for 2020: Any chance we could disable comments on anything relating to HSCT moving forward?
1) Pro views are very entrenched.
2) It is sucking up lots of our time as reader, diluting our attention span. We now have to go through dozens of comments every day to find that one that adds value.
3) It is sucking up a lot of your bandwidth.
Controversial I know, but a procedure on the scale of HSCT should be undebatable. i.e. bullet-proof data on risk and efficacy. Until then, lots of ink, emotions, false hope, pontification and blind/false belief.
From memory (could be wrong here) but you have disabled comments relating to Zamboni for a while many years ago, at the peak of his now-defunct prophecy.
You evidently feel threatened by the other side of the debate. A lot of the pro HSCT responses are correcting half truths and misinformation.
I think Tony Fonda is asking the HSCT proponents to show us the data. It is clear that HSCT-proponents are behaving like religious zealots and are not prepared to accept that we don’t have the necessary confidence in the data on the risks of HSCT to weigh-up against its benefits. This is how all treatment decisions are made and not on blind faith.
At least the blog is trying to put things in perspective. There are other ways of managing MS apart from HSCT; you need to accept this position which is not unreasonable.
But the data is there; HSCT has been used for over 20 years to treat MS – that’s a lot longer than many DMTs. There have been considerably fewer deaths from HSCT than there have been as a result of many DMDs – those who have died from PML after Tysabri, for instance.
When you have to resort to name-calling you’ve pretty much lost any credibility.
We are not referring to efficacy, but relative efficacy in properly performed single-blinded head-2-head studies and the relative risks compared to say alemtuzumab, cladribine, ocrelizumab, natalizumab, etc. We also need proper long-term data, for example, the cancer risk I refer to in this post. The reason why the MS community seems loathe to adopt HSCT is primarily due to a lack of data and not some conspiracy theory. Compare this to the adoption of off-label rituximab use; rituximab is supported by data that the MS community finds convincing hence is prepared to stick its head above the parapet and prescribe.
Do your really.believe this
“Do your really. believe this”
Do you mean: “Do you really believe this?”
If that is what you mean, then yes.
Tony, you make a very good point! No comments may be the only way to deal with the issue. Interestingly, based on IP addresses it is really only 3 commentators that make over 90% of the pro-HSCT comments. Contrary to one’s impression, there is no army of HSCT supporters on the blog and hence the pro-HSCT movement is very similar to the CCSVI movement.
It may be only 3 who regularly comment on this forum, but you can’t really compare the number of pro-HSCTers with the debunked CCSVI movement. HSCT is an accepted first or second line treatment in many countries. When was CCSVI ever available on the NHS? Hardly the same thing, Gavin!
I can and did – when referring to your zeal that is. It is tiring Alison. Less is more.
Le silence est d’or et la parole est d’argent
And merry Christmas to all, the 3 die-hard HSCTers included.
I simply respond, Gavin – you provoke us with your name calling and just expect us to say nothing.
Let’s see what the outcome of BEAT-MS and STAR-MS are (given the fact that you choose to ignore the data that King’s, Mexico, Russia etc have gathered on HSCT for progressive MS patients).
I agree that less is more – and that’s why I’m baffled that you insist on these posts attacking the HSCT Community every couple of weeks or so! Not the practitioners, not the hospitals that provide it – the HSCT community! What possible benefit can be gained from that?
Absolutely, there are risks from HSCT (patients sign a disclaimer to indicate that they understand this – my husband certainly did at King’s), but for many those risks are outweighed by the potential benefits. If you want to correct misconceptions and inaccuracies, that’s admirable – but you should certainly include the Neurological community as they are not exempt when it comes to perpetuating inaccuracies about HSCT.
I can’t speak for the HSCT community, but I extend to you a Merry Christmas too. It would be nice to call a Christmas truce – you’re right that this is tiring!
We are referring to the zealotry of the believers. On a zealotry scale of 0 to 10 the core groups of CSVIers and HSCTers score 10. What makes them similar is their utter conviction that they have found the solution for treating MS. Unfortunately, the reality is very different.
You really need to take off your blinkers and try and see the woods rather than the trees. HSCT is just another high-risk DMT, nothing more nothing less. Similar issues arise when it comes to using HSCT in clinical practice; i.e. eligibility, relative benefits, relative risks, fertility, family planning, monitoring, etc. Its is part of our Barts-MS treatment algorithm and sits alongside cladribine and alemtuzumab as an IRT. There is nothing magical about HSCT. I suspect as far as relative efficacy goes it sits just above alemtuzumab. HSCT will be cheaper than alemtuzumab which is why it may in the future get wider adoption in the UK than other countries. As you are aware the NHS is very cost-sensitive. However, I doubt the EMA and NICE will allow HSCT to be used first-line. The latter won’t be for lack of trying; I for one think it should be available 1st-line.
Similar to other DMTs HSCT’s effectiveness falls with disease duration; unfortunately, it does not stop smouldering MS. I follow several patients who are NEDA-2 post-HSCT who are gradually getting worse. On the other hand I follow a few patients who have had HSCT early and are doing well. These results are similar to what we see with alemtuzumab. The data really doesn’t differentiate HSCT from alemtuzumab, which is why the NHS is funding a head-2-head study. Can we please wait for the results of this study?
A patient who received HSCT for RRMS at Clinica Ruiz in 2016 just passed away from leukemia on 12/10/19. Her husband said oncologists told him they are certain the leukemia was from cyclophosphamide she recurved during HSCT. I’m pro-HSCT, but really wish people would quit down playing the risks. There are risks with HSCT just as there are risks with DMTs. You can’t do a proper risk-benefit analysis by ignoring risks.
Well if you look hard enough you will find it
Malignancies After HSCT
Conditioning for HSCT, pretreatment with alkylating substances, and the AD itself may contribute to an increased risk for the development of malignancies after HSCT in these patients. Cy and irradiation used for conditioning are both known to induce malignancies in a dose-dependent manner. Cy has been associated with bladder carcinoma (45) and the development of hematological malignancies (46). In an analysis of 700 patients with severe aplastic anemia treated with allogeneic marrow transplantation, 23 developed a malignancy 1.4 to 221 mo (median, 91 mo) after transplantation. Five cases were lymphoid malignancies occurring 1.4 to 14.6 mo (median, 3 mo) after transplantation, and 18 were solid tumors presenting 30 to 221 mo (median, 99 mo) after transplantation. Radiation was identified as significant risk factor for the development of a malignancy (47). Similar conditioning protocols have been used in patients with ADs, albeit before autologous HSCT. However, it must be considered that patients with ADs differ from patients with hematological and malignant diseases undergoing HSCT, not only with respect to diagnosis but also with respect to pretreatment before HSCT. In the latest review of the Promise database, 5 of 900 patients who received HSCT for an AD developed a malignancy after transplantation. Diagnoses were acute myeloid leukemia (MS), bronchial carcinoma (SSc), esophageal carcinoma (SSc), refractory anemia with excess of blasts (SLE), and posttransplant lymphoproliferative disease (mixed connective tissue disease) (1). Longer follow-up in prospective trials is needed to identify patients with ADs who are at increased risk for malignancy after HSCT. Regular urine examinations may help to early detect Cy-induced bladder carcinoma.
Complications of autologous hematopoietic stem cell transplantation for patients with autoimmune diseases
https://www.nature.com/articles/pr201157