Tuesday, 19 January 2016

Guest Post: Basil Sharrack and John Snowden



    Basil Sharrack (Neurologist) and John Snowden (Haematologist)

Haematopoietic stem cell transplantation (HSCT) has been used as treatment for MS since the mid-nineties. The aim of this treatment is to reboot the immune system using chemotherapy which destroys the defective immune cells driving the inflammation in the brain and spinal cord and rebuilds a regenerated immune system from the patient's own blood stem cells, with greater numbers of naïve and regulatory immune cells.

Within the European Society for Bone Marrow Transplantation Registry, more than 800 patients have undergone this treatment, and elsewhere around the world prospective clinical trials have been reporting.

The largest reported case series is from Northwestern University in Chicago which included 145 patients (123 with RRMS and 28 with SPMS). There was not a control treatment arm but in patients with RRMS, AHSCT was linked to improved disability in 64% of the patients who were followed up. Of those patients who were followed for 4 years, 80% were relapse-free and 87% were disability progression-free. There was a significant decrease in T2 lesion volume and a significant improvement in the quality of life scores. There was no treatment related mortality. The treatment was less effective for patients with secondary progressive MS or those who had MS for more than ten years, highlighting that this treatment works most effectively in patients with early inflammatory disease.

The Chicago group, led by Dr Richard Burt, are now leading an international multicentre randomised clinical trial (the MIST trial) to compare AHSCT against FDA approved disease modifying agents as a second line treatment in patients with RRMS who have had two or more significant relapses in the previous 12 months despite the use of disease modifying agents. The Royal Hallamshire Hospital in Sheffield is one of four international centres running this trial.

Basil and John

References





CoI: None declared


For further information on ASCT treatment and the research trial, please see www.sth.nhs.uk/panorama (CLICK) or call  0114 2715934.

14 comments:

  1. Not much to see here then. Would,ve been good to hear their personal experience of this trial so far, particularly now its made such a splash on the Beeb. Also an indication of complications following the procedure would've been good as not really mentioned last night.

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    1. That's what I thought it's 'something and nothing'.

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    2. Love that word! Pabulum indeed!

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  2. "Of those patients who were followed for 4 years, 80% were relapse-free and 87% were disability progression-free."

    Just a thought: That except in itself says nothing to me. I believe I could have fallen into that bracket during some earlier periods of my _untreated_ "PPMS". But it is indeed stated that the treatment is less effective for progressive MS. I certainly won't be asking for this treatment.

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    1. Same here. None of us untreated pwMS have been in a study so how can its efficacy be proven. I hope it does work, but if it is only for RRMS, what does that tell us?

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  3. From your article:

    "On the horizon are other agents, all aimed at the
    early inflammatory phase (for example, cladribrine, alemtuzumab,
    teriflunomide, laquinimod, fumaric acid, ocrelizumab
    and daclizumab), but those tested in a small
    population of SPMS (cladribine and alemtuzumab) failed
    to show effectiveness."

    It seems the drugs Team G are pushing (cladribine and alemtuzumab) are not so good for SPMS.

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    1. We've highlighted repeatedly that one question one has to ask when looking at a "failed trial" is whether suitable outcome measures were used. To focus on ambulation in pwMS who are in the upper half of the EDSS (and EDSS is ambulation-biased, certainly between 4-7.5) may not be the most sensible thing to do. Check yesterday's and previous (and future!) posts on upper limb function. This is not to say that all DMTs mentioned have a similar chance (or degree) of success in pwSPMS. There is a rationale for Cladribine, and that is CSF penetration over and above its peripheral effetcs on lymphocyte number and function. The study by Rice, et al. 2000 is often quoted as a "negative trial", but effects on MRI were evident, and for clinical outcomes it was too short (1 year).

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  4. what this tells us is that we are no closer to a cure than we were before, but at least they're trying.

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    1. If may depend on when you start...too late and it may be too late.

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    2. I trust you refer here only to this HSCT stuff. Otherwise: Neuroprotectives please! Please! Don't abandon us progressives! Anyway, according to some schools of thought - as far as I understand - the progression is there from the beginning and is the core of the disease. Either neuroprotectives or a successful outcome in the Charcot project is what I hope for, dream of. But perhaps I am also partly resigned, as I roll onto 40 years old with over 15 years of PPMS under my belt, of the fact that it may all come too late for me. "Just the way it is", is what I say to myself.

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    3. The point I was making as in response to the no closer to a cure and was saying if you start RRMS treatment early it may never develop further. It is a hypthesis that needs data

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    4. Yes. I just think that, if a therapy required a time window which may never present itself in many people, i.e. in cases of "PPMS", it could never be hailed as a "cure".

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  5. Thanks to our guests Basil and John for this post. It will be interesting to hear how the trial progresses please do keep us all updated. Probably not much help directly to many people following this blog but we wish all the young MSer participants well and it would be brilliant if they become MS free and never need to join us here! Thanks for all your hard work, every bit of research counts in this battle we are in together.

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