Saturday, 17 June 2017

HSCT in Progressive MS

Cull G, Hall D, Fabis-Pedrini MJ, Carroll WM, Forster L, Robins F, Ghassemifar R, Crosbie C, Walters S, James I, Augustson B, Kermode AK. Lymphocyte reconstitution following autologous stem cell transplantation for progressive MS. Mult Scler J Exp Transl Clin. 2017 Mar 23;3:2055217317700167

BACKGROUND: Autologous stem cell transplantation (ASCT) for progressive multiple sclerosis (MS) may reset the immune repertoire.
OBJECTIVE:The objective of this paper is to analyse lymphocyte recovery in patients with progressive MS treated with ASCT.
METHODS: Patients with progressive MS not responding to conventional treatment underwent ASCT following conditioning with high-dose cyclophosphamide and anti-thymocyte globulin. Lymphocyte subset analysis was performed before ASCT and for two years following ASCT. Neurological function was assessed by the EDSS before ASCT and for three years post-ASCT.
RESULTS:CD4+ T-cells fell significantly post-transplant and did not return to baseline levels. Recent thymic emigrants and naïve T-cells fell sharply post-transplant but returned to baseline by nine months and twelve months, respectively. T-regulatory cells declined post-transplant and did not return to baseline levels. Th1 and Th2 cells did not change significantly while Th17 cells fell post-transplant but recovered to baseline by six months. Neurological function remained stable in the majority of patients. Progression-free survival was 69% at three years.
CONCLUSION:This study demonstrates major changes in the composition of lymphocyte subsets following ASCT for progressive MS. In particular, ablation and subsequent recovery of thymic output is consistent with the concept that ASCT can reset the immune repertoire in MS patients.

                               We have more in common than that which divides us

This is yet more evidence that some people with progressive MS, benefit from immune modulation. Is it the T cell or the B cell.

6 comments:

  1. Great job Dr Mouse
    Question: this B cell overshoot is copy cat Alemtuzumab ?
    And also this "blast from the past"
    http://multiple-sclerosis-research.blogspot.com/2017/05/blast-from-pastmemory-b-cells-depleted.html
    Also in the post study the b cell count is the total ? No differentiation between mature cd 19 or memory ?
    Thanks Luis

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  2. Very interesting study. Surprised to see that the three-year progression free survival rate was 69%. That's very impressive, given that this was a population of patients with progressive ms.

    Since I don't have access to the full paper, what flavor of progressive MS did these patients have? I'm assuming it was a population of SPMS patients who still had evidence of active inflammation, as the abstract states they had failed traditional treatment options. I'm assuming that, since later stage SPMS and the large majority of PPMS patients don't have active inflammation, and thus are not offered traditional treatments, that the patient population in this study would be SPMSer's with active inflammation.

    Even so, the 69% progression free rate is pretty impressive. I recall another longitudinal study that found a 33% rate of progression free survival at five years for patients with SPMS. I believe this was a European longitudinal study published sometime within the last 12 months…

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  3. Actually, was able to access full paper. Study size was small, only 13 patients. Mix of PPMS and SPMS, but at least one of the PPMS patients had gadolinium enhancing lesions prior to undergoing HSCT.

    Paper didn't include a breakdown by subset as to progression free survival rates. Would love to know which patients fared best, but I didn't see that data available.

    Given the burgeoning HSCT medical tourism industry, which is not excluding patients with progressive disease, some larger, more robust studies on the efficacy of HSCT in patients with various forms of progressive MS are urgently needed. If this treatment can induce years of stability in patients who otherwise would see disability progression, the MS community urgently needs to know this info. If HSCT only works on patients with progressive ms who display active inflammatory markers, this also needs to be shown.

    Given the moderate effects of Ocrevus on even progressive patients with active inflammatory markers, a treatment modality that can put a halt to progression for years at a time warrants robust investigation.

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  4. WC brings up an important point. If effective in progressive disease, especially in non enhancing lesions, it would point to another available treatment for this resistant patient population. Dr Saccardis recent paper with Muraro also showed a 50%PFS with a mix of RRMS and SPMS patients. Is the B cell depletion doing this because this does mention T cell repertoire change? Interesting to see larger studies.

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  5. 70% EDSS progression free is probably approximately what would be expected with a placebo. People stay at EDSS 6.0 and 6.5 for years. I think wheelchair Kamikaze is right-any benefit would simply due to the effect on the immune system. Remember: There is no "stem cell therapy," only immune system destruction therapy. The "stem cells" don't do anything except ameliorate the side effects of the drugs.

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    Replies
    1. The problem is that the EDSS as currently formulated is not a linear scale, as you say many stay at EDSS 6-6.5 for a long time but it's only measuring mobility and not other issues such as potential cognitive decline etc. We need neuroprotectives.

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