Tuesday, 19 January 2016

London MS-AHSCT Collaborative Group

#MSRearch Eligibility Criteria for #HSCT #stem cell therapy

Professor Paolo Muraro and Dr Benjamin Turner have kindly provided this information on behalf of the London MS-AHSCT Collaborative Group (Chaired by Paolo Muraro and Majid Kazmi) about their current Eligibility Criteria for autologous haematopoietic stem cell therapy.

The London MS-AHSCT Collaborative Group have said that this is a working draft and may be amended in future as new or better evidence about AHSCT becomes available. However the important thing to note is that for consideration for inclusion to this form of treatment is it important that your MS is considered active.

The London MS-AHSCT have also stressed that they currently view this as an exceptional therapy for some people with MS, rather than a standard treatment; and that neither NICE nor NHS England have ‘green lighted’ this therapy for routine use in any form of MS.

If you are interested in this treatment it is important that you consult with your Neurology Team in the first instance.

Patient Eligibility Criteria Adopted by the London MS-AHSCT Collaborative Group 


The eligibility criteria are overall aimed at selecting patients who have failed approved treatments of high efficacy or have none available to them and have recently presented evidence of inflammatory CNS disease activity; and who could undergo AHSCT with an acceptable estimated level of risk of adverse events. Justification for each of criteria is supported by evidence from AHSCT trials and observational studies. 


Referral criteria: 
I. Diagnosis of MS made by a neurologist 

II. Able to walk, needing at most bilateral assistance to walk 20m without resting 

III. In relapsing MS (RMS), failed one licensed disease modifying drug of high efficacy (currently including alemtuzumab and natalizumab) because of demonstrated lack of efficacy 

IV. New MRI activity within last 12 months 

Inclusion criteria: 

1. Age 18 to 65 years 

2. Disease duration ≤15 years from diagnosis of MS 

3. Diagnosis of MS according to McDonald’s criteria 

4. For PPMS, CSF OCB+ 

5. For RMS, failed at least one licensed disease modifying drug of high efficacy (‘Category 2’ as defined by Scolding N, Barnes D, Cader S, et al. Pract Neurol 2015;15:273–279; currently including alemtuzumab and natalizumab) because of demonstrated lack of efficacy (as evident from relapse, MRI activity as defined below at Point 7, or EDSS increase) after being on DMT for at least 6 months

6. EDSS score 0-6.5 

7. Inflammatory active MS as defined by ≥1 Gd+ (>3mm) lesion (off steroids for one month) or ≥2 new T2 lesions in MRI within last 12 months 

8. Approved by the MDT 

Exclusion criteria

a. Eligible for an ethically approved clinical trial where AHSCT is offered as one of the treatment arms 

b. Unable to adequately understand risk and benefits of AHSCT and give written informed consent 

c. Prior treatment with total lymphoid irradiation and autologous or allogeneic hematopoietic stem cell transplantation London MS-AHSCT Collaborative Group - Patient Eligibility Criteria Final V.3. – 8/12/2015 

d. Contraindication to MRI including but not limited to metal implants or fragments, history of claustrophobia or the inability of the subject to lie still on their back 

e. Poorly controlled depression or recent suicidal attempt 

f. Presence of any active or chronic infection 

g. Unable to walk 20mt with or without support, or wheelchair dependent

h. Any significant organ dysfunction or co-morbidity that the Investigators consider would put the subject at unacceptable risk

20 comments:

  1. It is interesting that they have put in PPMS. But do they expect that it would not work if you are OCB-ve.

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    1. I believe it may speak to the diagnosis, but importantly showing there is immune activity on going.

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    2. I was diagnosed in 2010 with PPMS and interested in having hsct can u explain point 4 in the list i don't understand it

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    3. Point 4 refers to the presence of oligoclonal bands (antibodies present in the cerebrospinal fluid that surrounds the brain).

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  2. It is a great shame that the criteria relies on the MRI to determine disease activity. Latest research suggests that the MRI is not the best diagnostic tool for this as there is often hidden inflammation in SPMS and PPMS patients. This criteria excludes many who may be receptive to treatment. Beyond diagnosis, an MRI is irrelevant as lesions are simply a symptom of the disease.

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    1. Since the latest classification of MS by Lublin, et al. in 2014 the notion that PPMS should not be excluded a priori from DMT is gaining wider acceptance. MRI is key to assess treatment response, or lack thereof, so it does have an important role over and above diagnosis.

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    2. But what about the latest research from June 2015 on the subject of hidden inflammation? SPMS and PPMS patients may not show active lesions in an MRI but could still be receptive to HSCT. There is living, breathing, WALKING evidence of this, and yet your refusal to acknowledge it in the selection criteria effectively rules out those patients who don't tick your box. Active lesions are a symptom of MS in much the same way as optic neuritis or foot drop or whatever symptom you care to mention. There absence doesn't mean that HSCT won't work and the mother recent research supports that. Comments?

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    3. I agree that people with SPMS can have active lesions one sees this on post mortem.

      But you are berating the messenger as we are not the London-AHSCT collaborative, ProfG and DrK had suggested amenedments but as they are no in the collaborative (yet) they can't do anything.

      However this proceedure is not cost free, it has to be paid for by some trust and the data shows that the people most likely to benefit are people with active lesions that are visible. It does not say people without treatment wont benefit but if you look at the way they do the non myeoablative treatment they use clofarabine (Cladribine analogue), cyclophsphamide (cheap but makes you hair fall out and is nasty), sometimes rituximab, sometimes alemtuzumab and sometimes anti-thymocyte globulin the stem cells aid recovery of the risk of infection. So maybe
      clofarabine or cladribine may have some cost-effective benefit That is why DrK is proposing the cladribine studies

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  3. Can one pay for this treatment in the UK...?

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    1. Not yet - but that's on the way. Now that the UK neuros have put their heads above the parapet and admitted this is happening (under radar) on the NHS then private treatment is just a matter of time. It will cost between 70k and 90k.

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    2. Just to clarify - the activity doesn't just show up post mortem. Neurologists should be using the latest MRI scanners to identify inflammation which have got stronger and better over the yearsand this simply isn't happening! Whilst most clinics etc: might have a phase 3 or 4 strength scanner the latest phase 7. is by far better because it is able to show images that a phase 4 can not.The Sheffield trials use a 2.5! A TWO POINT FIVE!! Surely that's the Z X Spectrum equivalent of the MRI today. A bit of transparency about the strength of the London MRI would be interesting, wouldn't it? You cannot base treatment for SPMS and PPMS on such outdated technology when there is a far superior alternative out there. Thoughts?

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    3. MouseDoctor - what amendments to the criteria have Prof G and Dr K suggested, please?

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    4. I believe the 7T scanners are in Nottingham and Oxford and these are the current research scanners many standard MRI scanners are 3T or often less. In terms of London I believe best we are talking is 3T. I'm not aware of a london 7T.

      You can't base SPMS/PPMS treatment on outdated technology. I guess that technology is a neurologist:-)

      What amendments....sorry they are irrelevant. If the London Consortium want to change them they will change.

      I asked a neuro about cost and they said it costs NHS about 90K. If the haematologists have capacity should they offer it as a private service? However would them say yes to say people with progressive MS

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  4. It costs the NHS £30k not £90k.This was explicity stated in Panorama. Private treatment is being discussed and anywhere between £70k and £90k will be what one can expect to pay. They're hardly going to run it at cost/at a loss are they? The doctor that has mooted the £90k price tag hasn't even performed HSCT for an MS patient before - not a single one!

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    1. It was explicitly stated by the BBC...so a good source of info, but are you a spy. How do you know which doctor was asked...but Neuros are not doing the procedures it is haemtologists that are doing it however when you say cost to MS is £30K, is that the true cost?

      Maybe someone with access to charges can make it clear.

      We say cost of alemtuzumab is £7,000 per 12mg however the cost to the NHS is not just the cost of the drug. It is the cost of the infusion for a the week, the cost of the nurses etc to administer the drugs, the cost of the pharmacistis the cost of the steroids, the cost of the anti-virals the cost of the monthly monitoring of bloods, the tests, the monitoring of the urine, the cost of treating side-effects, 3% need thyroid survery, so cost of surgeons, etc, etc, etc.

      However the private costs are not hard to find for some of the stem cell docs. Does this include the after treatment care. If it is 90K will it fall foul of NICE because cost is at the centre of all this.

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    2. At 30K is it too much..bet it is even if it it is cost effective.

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    3. Sobering thought:

      At £7,000 per 12mg, Alemtuzumab is 25,675 times more expensive, by weight, than 24 carat gold.

      The world has gone mad.

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  5. Please can somebody tell me how to apply for this, I have searched the internet far and wide and cannot find any links to make enquiries or application, many thanks.

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  6. Hi!
    I have NMO (NEUROMIELITIS OPTICA) But I can walk (I'n in bed all day) I have lesion in T1 and T2. I live in Puerto Rico. My question is: I can apply?

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