50 Comments
Sep 20, 2021Liked by Gavin Giovannoni

I think patients should have equal control with Healthcare Providers. I believe that HSCT is more effective and cheaper for people with MS. I agree with msintheus that with the limitations of Ocrelizumab regarding vaccine antibodies, HSCT needs to be much more readily available both here in the UK and across the globe. HSCT has evolved and should now be considered a frontline treatment. Prof G, thanks for raising this important topic and also for admitting last week on twitter that your previous knowledge about HSCT abroad was out of date. This is so very rare for a Consultant to admit this. Thankyou from the bottom of my heart.

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author

But I am not the HSCT lead and really don't have time to keep up-to-date with foreign HSCT units' protocols. The person who actually told me that it was an HSCT-light programme was actually a prominent UK neurologist who runs an HSCT programme.

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author

But it doesn't change my opinion for that particular patient; I still wouldn't recommend she goes abroad for AHSCT.

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Sep 20, 2021Liked by Gavin Giovannoni

But not for the reasons you stated, presumably? The cyclophosphamide assumption was wrong (which was one of the reasons) and the Rituximab issue was wrong (another of the reasons).

Totally understand where you’re coming from in terms of people travelling overseas during a pandemic - I guess that the fact that they want to do that just goes to show how desperate they are for the help.

Incidentally - did you know that that particular patient’s neurologist told them they ‘use Lemtrada as part of their HSCT for MS protocol’? Another example of the utter rubbish that’s coming out of some mouths. If they don’t *know* for sure, then they shouldn’t say it!

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Sep 20, 2021Liked by Gavin Giovannoni

I think it’s important to double check that what you’re saying is accurate when so many could be influenced by it, but I can understand why you’d think that was the case when it’s coming from someone running an HSCT programme - it illustrates the need to ensure that every neurologist in the country has the facts from the top down. Your comment about Rituximab follow ups for two years after a patient returns home should also have been double checked before sharing it with your readers - I had several messages from people asking me if they need to source Rituximab when they get home. While that was once the procedure, it hasn’t been the case for 4 years now.

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We are very time-poor, me included, and keeping up-to-date with BMT/HSCT centres protocols is not a priority.

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I can imagine! But maybe the best thing to say, if you’re not absolutely certain, is nothing. There are so many untruths flying around in terms of HSCT overseas and it just helps to perpetuate that. Or you can always ask AIMS! (I’m only half joking!)

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Sep 20, 2021Liked by Gavin Giovannoni

Given the new - very serious risks of being on Ocrelizumab (no response to covid jab, covid increases mortality) I think AHSCT should be standard offer for a lot more people now. The global dynamics and risks/benefits have changed substantially and treatment guidelines should adapt accordingly.

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Sep 20, 2021Liked by Gavin Giovannoni

Should add to that I too would sign up for AHSCT tomorrow if offered

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Sep 20, 2021Liked by Gavin Giovannoni

I relapsed quite quickly after hsct. It was my first ms treatment after diagnosis. I have no regrets at all, although I do wonder where I will go from here. On paper I was the perfect candidate as per Dr Burts trial findings and the NHS criteria, I feel it is unfair this treatment locally is withheld from pw secondary progressive/ more advanced MS. Of the cohort who started treatment with me , I am the only one to have relapsed, the others are stable and some are thriving with much better quality of life.

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author

Maybe you need an induction-maintenance approach, i.e alemtuzumab followed by teriflunomide.

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Sep 20, 2021Liked by Gavin Giovannoni

My neurologist has applied for funding for lemtrada for me, but ocrevus or rituximab seem to be the recommended course of action by the AHSCT doctors. I’m not sure why. No doubt I need something, and I am glad to have options and forever grateful for this blog

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Sep 20, 2021Liked by Gavin Giovannoni

I would have AHSCT tomorrow, if I could. I am 44, a qualified Podiatrist and PhD Researcher. I want to work, I want a body that will allow me to do the things I used to. If AHSCT will reboot me… sign me up! My brain, brain stem and spine took a good frying before I was diagnosed and more lesions appeared after I started Ocrevus. I know it’s supposed to be “the wonder drug”; however, for me, I don’t feel any better. Yes, the last MRI showed NDA, my body disagrees. If anyone would like an AHSCT guinea pig or muse… 🙋🏼‍♀️🙋🏼‍♀️

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author

One of the problems once you are on a high efficacy therapy such as ocrelizumab is showing that you have ongoing inflammatory activity and are therefore eligible for AHSCT. If you can show breakthrough disease activity you may be eligible for AHSCT under the NHS treatment algorithm; assuming your MSologist will refer you.

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Sep 20, 2021Liked by Gavin Giovannoni

Many find themselves in a catch 22 situation when they sign up for Tysabri or Ocrevus - they tell us that they’re getting worse, they present clinically with further progression, but the MRI shows that the drugs are controlling activity (at least so far as the MRI is able to pick up) and they’re told ‘your MS is being controlled’ when it’s plainly not the case. This is soul destroying because these people know they’re getting worse but are ignored.

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founding
Sep 20, 2021Liked by Gavin Giovannoni

So much this. In fairness, it's unclear whether this group would make good candidates for HSCT (personally I am definitely not a clear cut candidate) so I can see where the doctors are coming from.

Still, unsure what to do about it. One part of me thinks to finish 4 rounds of ocrelizumab then switch to teri IF HSCT eligibility was a given on further activity.

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author

These pwMS may find this Newsletter helpful:

https://gavingiovannoni.substack.com/p/getting-worse

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Sep 20, 2021Liked by Gavin Giovannoni

Yes - I nearly used the world ‘smouldering’ in my reply and we do refer them to your articles on this topic.

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Sep 20, 2021Liked by Gavin Giovannoni

Would you like to take on a new patient and refer me? 😊

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author

Just asked to be referred to the HSCT leads at one of the London Neuroscience centres.

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author

I am not the HSCT lead at Barts Health NHS Trust; it is Dr Ben Turner.

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Sep 20, 2021Liked by Gavin Giovannoni

If only it was that simple! Many neurologists refuse to even make that referral!

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Sep 20, 2021Liked by Gavin Giovannoni

Might not be the right place to ask for this, but it was mentioned in the article so I'll give it a shot: are there any news on the state of the direct comparison trial Ocrevus/Lemtrada Vs AHSCT? The StarMS website doesn't have any updates on that (reckon the whole pandemic thing has influenced things)...

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author

We are currently prescreening patients at our centre.

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Sep 20, 2021Liked by Gavin Giovannoni

It’s good to read this, Gavin, and crucial that you’re continuing this conversation.

I do agree with your ethos that healthcare is a basic human right and that it should be free at the point of access, but I don’t think that’s a good enough reason for people not to go overseas when they have no other choice.

At AIMS we’re very aware of patients who have been unsuccessful in being accepted for HSCT on the NHS - but then told they can have it privately in the U.K. for £80k! Is it any wonder that they choose to go overseas for half the price? I know of one lady who could have afforded the private U.K. price tag, but went elsewhere on principle - if she was ‘unsuitable’ for HSCT on the NHS, then where were those principles when it came to getting it privately?

I’d argue that it isn’t social conscience that makes so many practitioners advocate against their patients going overseas - it’s a basic lack of knowledge about what’s being provided there. You yourself told how U.K. practitioners talk of ‘HSCT light’ in Mexico, and how ‘patients need to have follow up Rituximab for 2 years after they return home’ - neither of these things were accurate, and you had the good grace to correct them. I think many of those same practitioners would be surprised to know that the very doctor who they are belittling is a fellow of the Royal College of Physicians - are they?

Sadly you’re in the minority in that you’re happy to correct yourself when you get it wrong, and we need to re-educate practitioners about what’s actually on offer overseas. And of course that includes any risks as well as the benefits.

As far a a Citizens’ Jury is concerned, AIMS would love to be involved in your getting this off the ground - you’ve been talking about this for a long time now. So how about it? Can we work together on this? Can you email me at alison@aimscharity.org to discuss this further, Gavin? We have other plans that I’d like your input on too, if you have the time and the inclination!

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author

I have just sent the following email to people who I think can make this happen ad have copied in the biggest proponents of this treatment in the UK.

Dear ************

Please see my MS-Selfie Newsletter and comments from today on AHSCT as a treatment for MS.

https://gavingiovannoni.substack.com/p/ahsct-who-should-have-access

It raises many issues and I think this needs to be resolved at a wider level. Alison from AIMS would like to challenge us to set up a citizen's jury to deal with the issue. It would need to have all parties agreeing to it and sticking to it. Are you up for it? I do not have the bandwidth to take this on, which needs buy-in from the DoH, NHS-England, Neurologists, Haematologists, MS nurses and the MS patient communities.

With best wishes

Gavin

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Sep 20, 2021Liked by Gavin Giovannoni

Received and replied to - thank you, Gavin.

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author

Re: "At AIMS we’re very aware of patients who have been unsuccessful in being accepted for HSCT on the NHS - but then told they can have it privately in the U.K. for £80k!"

I would argue this is unethical and a conflict of interest if the same people are saying no on the NHS and yes in the private sector.

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Sep 20, 2021Liked by Gavin Giovannoni

Me too!

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Sep 20, 2021Liked by Gavin Giovannoni

Careful, GG, you're beginning to sound a little like an HSCT zealot, yourself! 😊 That's a good thing! I assume that by "zealot" you mean someone who is in favour of HSCT as a primary treatment for MS and doesn't mind saying so. That includes most of the thousands of pwMS who have actually had HSCT, as far as I can see.

By the way, before I went abroad at great expense for my HSCT in 2014, I consulted a local consultant haematologist and he would have been delighted to treat me here in Oxford, but was prevented from doing so by my intransigent neurologist. So that confirms your premise about where the stumbling block is in moving forward with access to HSCT in the UK. Until that access happens I'm afraid that pwMS will continue to go abroad for HSCT, and will continue to be helped by those you call zealots.

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author

A zealot is a person who is fanatical and uncompromising in pursuit of their religious, political, or other ideals. In this case HSCT for all pwMS regardless of their disease status, prognostic profile, etc. AHSCT is clearly not for all and even if it was available first-line, which I think it should be, a small minority will take it up as a treatment option.

The AHSCT zealots seem to be blaming me for the current status AHSCT has as a treatment for MS in the UK. I am not sure why.

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Sep 20, 2021Liked by Gavin Giovannoni

That’s baffling. You seem to be one of the only people willing to put your head above the parapet and actually have the conversation. We are grateful for the light you’re shining on this issue.

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Sep 20, 2021Liked by Gavin Giovannoni

I also want our position in AIMS to be stated very clearly here too; we are not advocating HSCT for all. But we do think that everyone with MS should have access to the information. We also believe that practitioners should be sharing accurate and up to date information with patients. Many are quoting incorrect mortality rates, stating that HSCT is only available in the U.K. for those with RRMS, or just plain refusing to discuss it. There is a real sense that many neurologists feel that their time is more important that the patient’s time (the irony - time is brain) and many are just downright rude. That all needs to change. I hasten to add that it isn’t the case with all neurologists, but it is a running theme with patients who seek our support.

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As a PWms of 30 years since diagnosis I would have jumped at the chance of any treatment, especially a potential cure. I fully understand that I am now excluded, on many levels, too late for the likes of me. It would reduce the need to find anything, anything that may help. CCSVI comes to mind for me and many others like me. You are driven into the arms of people offering unsubstantiated treatments. It’s amazing what desparation drives one too. So yes let PWms decide if they willing to take the risk on AHSCT. Life is a risk full stop. MS is like childbirth, in that it gives you the need to be courageous .

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Nice that you are talking about this,and next thursday 23/9/2021 its Autoimmune Diseases Working Party (ADWP)

And its free for all people

Here´s the program

https://www.ebmt.org/sites/default/files/document-center/ADWP%202021_Preliminary%20Programme_web14_0.pdf

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Sep 20, 2021Liked by Gavin Giovannoni

Prof, by the time HSCT becomes available first line, would you not expect a note promising drug to be coming closely behind it that is more targeted than the HSCT carpet bomb? You have talked previously about the differences between Alemtuzumab and HSCT. This would be an interesting newsletter article as their efficacy is considered on par yet the modes of action and therefore risk are very different

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author

Yes, AHSCT is an immunological nuke. I would prefer a heat-seeking missile with little collateral damage. The biggest problem apart from the early mortality risk with AHSCT is the infertility rate and the potentially very high secondary malignancy risk. Another problem is the delay in getting it going; it is not a treatment that you can start quickly, which often causes problems for people with very active MS.

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Sep 20, 2021Liked by Gavin Giovannoni

What is the actual risk of secondary malignancy?

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author

We don't know because MS data hasn't been collected or published yet. But from other disease areas, it is likely to be quite high. Cyclophosphamide is associated with a substantial risk of secondary malignancies.

This is what the SmPC states: https://www.medicines.org.uk/emc/product/3526/smpc#gref

Secondary Malignancies

As with all cytotoxic therapy, treatment with cyclophosphamide involves the risk of secondary tumours and their precursors as sequelae.

The risk of urinary tract cancer as well as the risk of myelodysplastic alterations, partly progressing to acute leukemias, is increased. Other malignancies reported after use of cyclophosphamide or regimens with cyclophosphamide include lymphomas, thyroid cancer, and sarcomas.

In some cases, the second malignancy developed several years after cyclophosphamide treatment had been discontinued. Malignancy has also been reported after in utero exposure.

The risk of bladder cancer can be markedly reduced by hemorrhagic cystitis prophylaxis.

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Sep 20, 2021Liked by Gavin Giovannoni

As you know, many of us with MS are willing to sacrifice length of life for quality of life. The PML infection could have killed me or worse still left me severely disabled before now.

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Sep 20, 2021Liked by Gavin Giovannoni

Yes healthcare should be free at point of contact and in an ideal world people wouldn't be forced to go for a procedure abroad; but the bottom line is we are being forced into this position. So many people in the UK are told that they aren't suitable because they are spms, ppms, no active lesions ect, it won't help them, and then go abroad and have it done and it's a successfully. Without a doubt Mexico and Russia for example are providing exemplary care and have much more experience in hsct for auto immune than we have in the UK. Many neurologists in this country are still misinformed and give out incorrect information to their patients, such as it's a new, experimental treatment with a high death rate ( I was told this 2 years ago and I attend a hospital that performs hsct!). I follow your blog very closely and I wish more neuros were open to discussion on the topic as yourself

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Sep 20, 2021Liked by Gavin Giovannoni

Thanks for Clarifying. Ideally the treatment would be made available in the UK to wider range of MS sufferers. However, if it’s proven to be affective abroad, but the NHS don’t offer AHSCT to patients at a certain stage, I back a person going abroad to get the treatment, if they can finance it. To my mind and at that stage, going abroad for treatment should not be frowned upon and the patient shouldn’t be left concerned about the amount and type of support he or she will get, when they return.

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Of course, I and most of my colleagues would support any of patients who decide to go the private route of care, be it in the UK or abroad. I look after several patients who have had HSCT via this route. I just don't make the referral for them. I hope you understand that it is a matter of principle. The same thing applies to private prescriptions for drugs that are not available on the NHS. In the past, I used to write them for my patients, but I have stopped doing this for several reasons

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Sep 20, 2021Liked by Gavin Giovannoni

Yes, as some one who had HSCT abroad, over 2 ½ years ago it should be available much sooner but I don’t agree with the criteria to qualify. I have been in remission from RRMS since my treatment. It used up a substantial amount from my husband’s pension fund and will now have saved the NHS money. I was diagnosed with CI in 2008 and formally with MS at the beginning of 2010. The first DMT was probably no better than placebo and in 2013 I relapsed leaving me having to be pushed in a wheelchair for 5 months; I say pushed because my left arm was also weak and fatigued very quickly. With the help of my MS nurse I had to fight against my neurologist to prove that I qualified for Tysabri. Under a different neurologist I was persuaded to come off Tysabri (and went onto Gilenya) after 2 years because of my PML risk. I relapsed and that’s when I started with problems with my right arm. I have an EDSS of 3 but still have significant problems with fatigue, dizziness, cognitive difficulties and my right arm and right leg in cold damp weather so obviously I wish that I’d been able to have a more effective treatment (that I hadn’t been persuaded to stop) much sooner. I went back on Tysabri but after another 2 years the neurologist once again scared the hell out of me over my high risk of a PML infection. I believe that a high risk of PML should be counted as a reason for HSCT (not just failure on an effective DMT). I had an episode at this time that I believe was a relapse anyway but my neurologist argued that it wasn’t (saying that there were no new lesions on my scan, which didn’t use Gadolinium). I was offered Lemtrada but when I saw a well respected neurologist privately he advised me not to take Lemtrada. I was not advised to avoid going abroad for treatment but was told that despite him seeing one new lesion on the MRI scan of my spine I did not qualify for treatment under the NHS. Unfortunately like many people the previous MRI scan of my spine had been carried out 2 years before (so even if there had been an active lesion or 2 new ones I still would not have qualified.)

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Sep 20, 2021Liked by Gavin Giovannoni

Is it unreasonable of me to bristle at the thought of a ‘citizens’ jury’ taking on the evaluation of this topic? In the era of widespread anti-vax beliefs, a culture where voting in a GE is treated with the same seriousness as choosing who wins the X Factor? I only want the highly educated and rational to be making these decisions.

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author

Citizen's juries are very democratic and work well. There is expanding literature on their uses and get rid of vested interests, etc.

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author

An important point why a neutral third party is needed is if the jury decides one way or another nobody can blame the other party. The HSCT zealots would have to accept that AHSCT is not for everyone and will be restricted to 2nd or 3rd line use. On the other hand, if the jury states that patients should have the option of AHSCT then the HCPs will have to offer it and refer patients for treatment regardless of their own position on the issue.

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Sep 20, 2021Liked by Gavin Giovannoni

I don’t think you’re wrong, as someone who travelled abroad for ahsct I was and continue to be shocked by the limited insight some of my fellow hsct’ers demonstrated with regard to the treatment they were undergoing, the potential adverse implications in the immediate and longer term, as well as having no reasonable expectations about what the treatment may achieve.

However, if there was a citizens jury approach making this an actual accessible option in the UK, perhaps it would allow for accurate information/education and assessment of individuals wishing to undergo it, by appropriately trained medical personnel, not wholly biased Facebook groups

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author

I suggest you read this BMJ Editorial on their potential role in healthcare.

https://www.bmj.com/content/357/bmj.j2650

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Sep 21, 2021Liked by Gavin Giovannoni

Excellent essay here and helpful. I think people in general have difficulty dealing with complex matters they want to see things in black and white terms, hence the strident camps supporting one DMT as the cure all for everyone. It seems like there is a large grey zone in terms of pwMS that were active and then successfully treated with Ocrevus. Potentially this treatment could backfire and it seems like we just do not have enough info on that.

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