Sunday, 15 February 2015

Replacing the immune system with stem cells inhibits relapsing disease

Mancardi GL et al. Autologous hematopoietic stem cell transplantation in multiple sclerosis: A phase II trial.
Neurology. 2015. pii: 10.1212/WNL.0000000000001329. [Epub ahead of print]

OBJECTIVE:To assess in multiple sclerosis (MS) the effect of intense immunosuppression followed by autologous haematopoietic stem cells transplantation (AHSCT) vs mitoxantrone (MTX) on disease activity measured by MRI.
METHODS: We conducted a multicenter, phase II, randomized trial including patients with secondary progressive or relapsing-remitting MS, with a documented increase in the last year on the Expanded Disability Status Scale, in spite of conventional therapy, and presence of one or more gadolinium-enhancing (Gd+) areas. Patients were randomized to receive intense immunosuppression (mobilization with cyclophosphamide and filgrastim, conditioning with carmustine, cytosine-arabinoside, etoposide, melphalan, and anti-thymocyte globulin) followed by AHSCT or MTX 20 mg every month for 6 months. The primary endpoint was the cumulative number of new T2 lesions in the 4 years following randomization. Secondary endpoints were the cumulative number of Gd+ lesions, relapse rate, and disability progression. Safety and tolerability were also assessed. Twenty-one patients were randomized and 17 had post baseline evaluable MRI scans.
RESULTS: AHSCT reduced by 79% the number of new T2 lesions as compared to MTX (rate ratio 0.21, p = 0.00016). It also reduced Gd+ lesions as well as the annualized relapse rate. No difference was found in the progression of disability.
CONCLUSION: Intense immunosuppression followed by AHSCT is significantly superior to MTX in reducing MRI activity in severe cases of MS. These results strongly support further phase III studies with primary clinical endpoints

This yet another study that if you deplete the immune system you can reduce disease activity. The mean 2.75 (range 0-8) new T2-weighted lesions on MRI scans compared to mean 12.75, range 2-34) in MTX-treated patients. AHSCT also outperformed MTX in annualized relapse rate (ARR) over 4 years. ARR was 0.19 for AHSCT patients and 0.6 for MTX patients (rate ratio = 0.36, 95% CI 0.15-0.88, p= 0.026).  So that is one relapse every 5 years or AHSCT which was better than Mitoxantrone, however it needs to be said this level of relapse rate has been achieved with less aggressive treatments in other studies and importantly this further shows that progression was not stopped. 57% of AHSCT patients demonstrated progression at the end of follow-up, whereas only 48% of MTX patients showed progression. The researchers did not observe any difference in Expanded Disability Status Scale (EDSS) scores between the two treatment arms.  So again it is more likely the earlier that treatents such as these are started the better


  1. Thanks for sharing this MD.

    Couple of important facts to note for context, for those reading it cold...

    1) The entire patient cohort was EDSS 6.0 or greater at the time of treatment

    2) They all had aggressive disease (had declined in the last year despite drug therapy).

    3) There were only 9 patients treated with HSCT

    4) Of the 9, only two were RRMS. 3 were SPMS, and four were SPMS with relapses.

    1. Yep just as I said the people with less disability and lack of progression are the people who will probably respond best to this type of treatment.


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