HSCT appears more effective than current MS drugs

Sormani MP, Muraro PA, Schiavetti I, Signori A, Laroni A, Saccardi R, Mancardi GL. Autologous hematopoietic stem cell transplantation in multiple sclerosis: A meta-analysis.Neurology. 2017 Apr 28. pii: 10.1212/WNL.0000000000003987. doi: 10.1212/WNL.0000000000003987. [Epub ahead of print]

OBJECTIVE:To summarize the evidence on immunoablative therapy followed by autologous hematopoietic stem cell transplantation (aHSCT) to manage severe and treatment-refractory multiple sclerosis (MS).
METHODS:We collected all the published studies of aHSCT in any form of MS from 1995 to 2016, carefully excluding reports that were updated in subsequent studies. Endpoints were transplant-related mortality (TRM), rate of disease progression, and no evidence of disease activity (NEDA) status. A weighted metaregression based on a Poisson model was run, assessing whether there were study-specific characteristics with an effect on TRM and progression.
RESULTS: Fifteen studies including 764 transplanted patients were pooled in the meta-analysis. The pooled estimate of TRM was 2.1% (95% confidence interval [CI] 1.3%-3.4%). TRM was higher in older studies (p = 0.014) and in studies with a lower proportion of patients with relapsing-remitting MS (RRMS) (p = 0.028). A higher baseline Expanded Disability Status Scale (p = 0.013) was also significantly associated with a higher TRM. Pooled rate of progression was 17.1% at 2 years (95% CI 9.7%-24.5%) and 23.3% (95% CI 16.3%-31.8%) at 5 years. Lower 2-year progression rate was significantly associated with higher proportions of patients with RRMS (p = 0.004). The pooled proportion of NEDA patients at 2 years was 83% (range 70%-92%) and at 5 years was 67% (range 59%-70%).
CONCLUSIONS: The emerging evidence on this therapeutic approach in MS indicates that the largest benefit/risk profile form this therapeutic approach can be obtained in patients with aggressive MS with a relapsing-remitting course and who have not yet accumulated a high level of disability.


If you want more definitive evidence that MS is immune-mediasted this is it. They have looked at all the studies and done a meta analysis of HSCT transplants from 1995-2016.

The NEDA (No Evident Disease Activity) rates of ablative haematopoeitic stem cells are high and higher than any of the current MS drugs. Importantly the people being put forward are more likely to be highly aggressive than the norm.

It is not surprising as you are taking a sledge hammer to the immune system. Removing it and replacing it and disease becomes silenced in many people. However, it fails in a significant proportion, is this because of brain activity not touched by the treatment or was the treatment started to late. This likewise justifies the pharma approach of attacking the immune system and so anyone that thinks these treatments do nothing are deluding themselves....(Bruv:-).

Likewise these studies are not blinded and so you can't definatively say that a drug woulddn't have worked as well, can yo do a head to head of ablative verses drug or ablative verses non-ablative HSCT.

However, likewise it should also be evident that this is not a cure for many and disease continues to progress. I would suggst this represents the damage accumulated burning along. Importantly, if you remove the immune system you are at risk from serious infection and the death rate of the studies was 2% (mean somewhere between about 1.5-3.5% with high confidence). So up to three deaths in a hundred people taking the treatment. However this is skewed because this was higher in the earlier studies, so the figure can be used to make the proceedure more alarming.

A James Lind Alliance question of the MS Society is can early aggressive treatment stop disease and the ultimate aggressive treatment would be to perform HSCT as the first treatement straight from diagnosis. Would you be willing to risk this treatment? It is clear many Neurologists wouldn't, but should it be their choice?

Why do I say this, if a neurologist would not be willing to use alemtuzumab early they are unlikely to go for HSCT.

Casanova B, Jarque I, Gascón F, Hernández-Boluda JC, Pérez-Miralles F, de la Rubia J, Alcalá C, Sanz J, Mallada J, Cervelló A, Navarré A, Carcelén-Gadea M, Boscá I, Gil-Perotin S, Solano C, Sanz MA, Coret F.Autologous hematopoietic stem cell transplantation in relapsing-remitting multiple sclerosis: comparison with secondary progressive multiple sclerosis.
Neurol Sci. 2017. doi: 10.1007/s10072-017-2933-6. [Epub ahead of print]

The main objective of our work is to describe the long-term results of myeloablative autologous hematopoietic stem cell transplant (AHSCT) in multiple sclerosis patients. Patients that failed to conventional therapies for multiple sclerosis (MS) underwent an approved protocol for AHSCT, which consisted of peripheral blood stem cell mobilization with cyclophosphamide and granulocyte colony-stimulating factor (G-CSF), followed by a conditioning regimen of BCNU, Etoposide, Ara-C, Melphalan IV, plus Rabbit Thymoglobulin. Thirty-eight MS patients have been transplanted since 1999. Thirty-one patients have been followed for more than 2 years (mean 8.4 years). There were 22 relapsing-remitting multiple sclerosis (RRMS) patients and 9 secondary progressive multiple sclerosis (SPMS) patients. No death related to AHSCT. A total of 10 patients (32.3%) had at least one relapse during post-AHSCT evolution, 6 patients in the RRMS group (27.2%) and 4 in the SPMS group (44.4%). After AHSCT, 7 patients (22.6%) experienced progression of disability, all within SP form. By contrast, no patients with RRMS experienced worsening of disability after a median follow-up of 5.4 years, 60% of them showed a sustained reduction in disability (SRD), defined as the improvement of 1.0 point in the expanded disability status scale (EDSS) sustains for 6 months (0.5 in cases of EDSS ≥ 5.5). The only clinical variable that predicted a poor response to AHSCT was a high EDSS in the year before transplant. AHSCT using the BEAM-ATG scheme is safe and efficacious to control the aggressive forms of RRMS.


This is another HSCT study published after the review will have been done.  Again this suggests the earlier you start the more likely the procedure will suceed and is more suitable for RRMS.

Labels: