Saturday, 3 December 2011

Bone marrow transplantation (BMT)

Epub ahead of printMancardi et al.  Autologous haematopoietic stem cell transplantation with an intermediate intensity conditioning regimen inmultiple sclerosis: the Italian multi-centre experience. Mult Scler. 2011 Nov 29. 

Background: Over recent years numerous MS'ers with severe forms of MS refractory to conventional therapies have been treated with intense immunosuppression followed by autologous haematopoietic stem cell transplantation (AHSCT). The clinical outcome and the toxicity of AHSCT can be diverse, depending on the various types of conditioning (chemotherapy) protocols and on the disease phase.

Objectives: To report the Italian experience on all the consecutive patients with MS treated with AHSCT with an intermediate intensity conditioning regimen, named BEAM/ATG, in the period from 1996 to 2008.

Methods: Clinical and magnetic resonance imaging outcomes of 74 MS'ers were collected after a median follow-up period of 48.3 (range = 0.8-126) months.



Results: Two MS'ers (2.7%) died from transplant-related causes. After 5 years, 66% of patients remained stable or improved. Among patients with a follow-up longer than 1 year, eight out of 25 subjects with a relapsing-remitting course (31%) had a 6-12 months confirmed EDSS improvement > 1 point after AHSCT as compared with one out of 36 (3%) patients with a SP disease course (p = 0.009). Among the 18 cases with a follow-up longer than 7 years, eight (44%) remained stable or had a sustained improvement while 10 (56%), after an initial period of stabilization or improvement with median duration of 3.5 years, showed a slow disability progression.

Conclusions: This study shows that AHSCT with a BEAM/ATG conditioning regimen has a sustained effect in suppressing disease progression in aggressive MS cases unresponsive to conventional therapies. It can also cause a sustained clinical improvement, especially if treated subjects are still in the relapsing-remitting phase of the disease.

"These results confirm what we know already that in MS'ers with aggressive disease BMT works; however it comes with a very high mortality. The chance of dying from the procedure is in the order of 1 in 40. Are you prepared to take these risks?"

"I personally think other treatment options are safer than this, for example Natalizumab and Alemtuzumab."

CoI: multiple

6 comments:

  1. I read somewhere that the average life expectancy after diagnosis is 30 years - so the timebomb is ticking. QoL can be diminished - see Debbie Purdy etc. So the mortality rate doesn't scare me too much - MS is scary. More worrying is that some continue to progress after a period. Would really be useful if the MS researchers could improve prognosis and to work out why, after this treatment, some still progress.

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  2. Yes, the risks of dying are high, but progressive MS is a slow, horrible and dragged-out version of the same thing.

    It's pretty clear to me that after 6 years of PPMS I am not going to get any better. There is a pipe-dream that scientists mat be able to one day slow the progression but if that's the best I can look forward to then I'd rather opt for a risky treatment option that could offer immediate results.

    There does seem to be a cruel inevitability to progressive MS.

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  3. Prof G,

    Interesting article on immuno-suppressants posted on the MRSC website:

    http://www.msrc.co.uk/index.cfm/fuseact ... pageid/683

    Most of the experts consider that neuro-protective agents are needed in addition to anti-inflammatories. Do you share this view? I saw your earlier comment on a pathology presentation and how basic facts about the disease need to be re-visited.

    Thanks

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  4. The very same article states that: "In the European experience, the mortality due to AHSCT fell from 7.3% in the years 1995–2000 to 1.3% in the 2001–2007 period, probably due to a better selection of patients and avoidance of high-intensity condi- tioning regimens."
    The 2.7% TRM is a retrospective value for a cohort that goes back to 1996. Recent reviews state that management of BMT has vastly improved over the last years; that TRM is dependent on a center-effect and that in experienced centers it is now considered to be consistently lower than 1%. We are not so far from PML rates in some natalizumab-treated patients; and contrary to natalizumab BMT offers the prospect of halting the disease (at least for early RRMS patients), inducing medicatin-free remission, not only slowing it down. Also, natalizumab doesn't even have this kind of long-term follow-up yet, so nobody can really pretend to know its long-term effects.

    This is all without taking into account the 'added benefit' consistently reported in all BMT studies, namely a good chance of allowing regeneration and obtaining some disability reversal - something no DMT currently offers, apart from anecdotical reports.

    So the benefit/risk calculation should really be left to patients. 1% TRM for a shot at long-term remission or even cure, coupled sith some degree of disability reversal, could be a very fair gamble for many,

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  5. BMT depletes the cells of the immune system and they are created from scratch from the bone marrow. That means they have all the putative genetic deficits needed for the re-occurrence of MS (ie HERV code)

    However, we are constantly told that environmental factors are always needed for the MS to develop (ie in the form of EBV virus infection and/or vitamin D deficiency).

    So the re-establishment of MS following BMT would mean one thing: that the environmental factors worked their way again, ie the patient was infected again by EBV and/or continues to have low levels of vitamin D. Testing of BMT treated patients should reveal no EBV virus prior to deterioration, only afterwards.

    Did anyone check this out?

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