Interim trial results: Bone Marrow Stem Cell Replacement Therapy

Is  hematopoietic stem cell transplant a realistic treatment for MS? #MSBlog #MSResearch

“We are aware that a lot of readers of this blog are proponents of more aggressive therapy. The abstract below is the interim, or 3-year, results of the international autologous hematopoietic stem cell transplant (HCT) trial. The results are very encouraging. Please note that this is an open-label study and hence it is difficult to draw comparisons with other licensed DMTs. NEDA rates at 3-years were a remarkable 78%; higher than any of the licensed DMTs. HCT is not a licensed therapy for MS and hence cannot be offered as part of routine care; at least this is the situation in the UK. How do we get HCT licensed for treating MS? A difficult question; I suspect the community would need to do a head-2-head study against a licensed therapy. I would think the best comparator here would be alemtuzumab considering the potential risk of HCT. It is clear that when HCT is done in specialist units it is much safer than previous studies have suggested.”

“These results mirror those of the Canadian BMT collaborative that have been presented at meetings, but have yet to be published in a peer-review journal. On my recent visit to Canada I was told that both Ottawa and Calgary are now providing HCT as a treatment option for MSers who have very active MS and have failed all DMTs. I would be interested to know if their guidelines will include alemtuzumab as it has recently been licensed in Canada.”

“Will HCT work for progressive MS? I suspect it will have the same effect as other highly active drugs have in MSers with progressive MS; i.e. it will stop focal MRI activity, prevent any superimposed relapses, but it won’t necessarily stop the gradual progression that defines this phase of disease. Unfortunately, we don’t have enough long-term data on whether or not there is therapeutic lag with BMT/HSC. However, based on the published trials of BMT in progressive MS most MS centres doing BMT have stopped using BMT/HSC in progressive MS and reserve it for treating early relapsing disease. A situation that is not dissimilar to how we use alemtuzumab.”

“What is the difference between autologous bone marrow (BMT) and autologous hematopoietic cell (HCT) transplant? In BMT the stem cells are harvested via a bone marrow aspirate and with HCT they are taken from the peripheral blood after they are mobilised from bone marrow using chemotherapy and in some instances growth factors.”

A bone marrow aspirate

Epub: Nash et al. High-Dose Immunosuppressive Therapy and Autologous Hematopoietic Cell Transplantation for Relapsing-Remitting Multiple Sclerosis (HALT-MS): A 3-Year Interim Report. JAMA Neurol. 2014 Dec 29.

Background: Importance Most patients with relapsing-remitting (RR) multiple sclerosis (MS) who receive approved disease-modifying therapies experience breakthrough disease and accumulate neurologic disability. High-dose immunosuppressive therapy (HDIT) with autologous hematopoietic cell transplant (HCT) may, in contrast, induce sustained remissions in early MS.

Objective: To evaluate the safety, efficacy, and durability of MS disease stabilization through 3 years after HDIT/HCT.

Design, Setting, and Participants: Hematopoietic Cell Transplantation for Relapsing-Remitting Multiple Sclerosis (HALT-MS) is an ongoing, multicenter, single-arm, phase 2 clinical trial of HDIT/HCT for patients with RRMS who experienced relapses with loss of neurologic function while receiving disease-modifying therapies during the 18 months before enrolling. Participants are evaluated through 5 years after HCT. This report is a prespecified, 3-year interim analysis of the trial. Thirty-six patients with RRMS from referral centers were screened; 25 were enrolled.

Interventions: Autologous peripheral blood stem cell grafts were CD34+ selected; the participants then received high-dose treatment with carmustine, etoposide, cytarabine, and melphalan as well as rabbit antithymocyte globulin before autologous HCT.

Main Outcomes and Measures: The primary end point of HALT-MS is event-free survival defined as survival without death or disease activity from any one of the following outcomes: (1) confirmed loss of neurologic function, (2) clinical relapse, or (3) new lesions observed on magnetic resonance imaging. Toxic effects are reported using National Cancer Institute Common Terminology Criteria for Adverse Events.

Results: Grafts were collected from 25 patients, and 24 of these individuals received HDIT/HCT. The median follow-up period was 186 weeks (interquartile range, 176-250) weeks). Overall event-free survival was 78.4% (90% CI, 60.1%-89.0%) at 3 years. Progression-free survival and clinical relapse-free survival were 90.9% (90% CI, 73.7%-97.1%) and 86.3% (90% CI, 68.1%-94.5%), respectively, at 3 years. Adverse events were consistent with expected toxic effects associated with HDIT/HCT, and no acute treatment-related neurologic adverse events were observed. Improvements were noted in neurologic disability, quality-of-life, and functional scores.

Conclusions and Relevance: At 3 years, HDIT/HCT without maintenance therapy was effective for inducing sustained remission of active RRMS and was associated with improvements in neurologic function. Treatment was associated with few serious early complications or unexpected adverse events.

HALT-MS is a prospective, open-label, single-arm, multicenter phase 2 clinical trial ( Identifier: NCT00288626).

CoI: multiple; the Royal London Hospital referred patients to the Imperial College Hospital for potential inclusion in this study.

About the author

Prof G

Professor of Neurology, Barts & The London. MS & Preventive Neurology thinker, blogger, runner, vegetable gardener, husband, father, cook and wine & food lover.


  • So far we do not have an approved therapy for PPMS ; do you think if HSCT is performed early in the PPMS disease course (even with no MRI enhancing lesions ) and with a low EDSS HSCT could work ?
    Fingolimod recently failed and you suggested in a previous post that we probably need a more powerfull DMT , "PPMS is very inflammatory "and "Ocrelizumab is likely to be a more potent anti-inflammatory than fingolimod " so why there is no trial with HSCT and PPMS ?
    I thought HSCT is the most powerful anti inflammatory therapy.

    • I would suspect no based on the the repeated failures of peripheral immunosuppression……..HSCT is peripherhal immunosuppression in the extreme but again it is not clear that this is dealing with progressive MS. The immunodepletion does not necessarily remove the CNS immune componentin people with progressive MS

    • MD,

      is there anything to say that the immune activity is the brain in progressive disease is just the mopping up of debris from degenerating axons etc? What are the B cell clusters doing and why is there meningeal inflammation? Could meningeal inflammation also be a response to breakdown products in the CSF?

    • (i) Maybe you could be right inflammatory responses in brain could be to clear up damage.
      (ii) B cell cluster what re they doing…producing antibodies and presenting antigen? but many people do not believe in them as a significant occurrence.
      (iii) Meningeal inflammation occurs because they are recruited to this place but is it (iv) a damage mop up or a damaging response.

      The inflammatory response in the CNS has largely not been adequately targeted I believe.

      When it is…..if MS gets better you get the answer on balance and if worse you the answer on balance. Some people claim this inflammation is a good thing I suspect not.

    • To the original poster…
      See link below which includes some interesting results for SPMS and PPMS in Moscow under Dr Novik & Federenko. There are several PPMS patients from Moscow who've seen very positive results and EDSS improvements.

    • many of the folks who have been to Russia have blogs, and there is the Australia 60 Minutes piece as well.

      it seems there is a waiting list. the early results seem promising, and so will be great if this continues. perhaps then it would be looked at more. I really wish MS patients had a say in MS research budgets as this should be funded more versus other areas. U.S., European, Australian researchers should be trying to replicate this research (there are some journal articles on the above Russian approach). As it stands now each of us needs an ice bucket challenge to raise money for overseas HCST. We really should pool together and help Dr. F and their team expand their facilities.

  • Profs – Happy NewYear. Thanks for this positive post. A mixed year – highlight was probably Alemtuzumab becoming available on the NHS. Low point – Gilenya not having an impact on PPMS (plus the sad death of Debbie Purdy). What will 2015 bring? I hope for some positive news on the Charcot project, some positive news on a neuro-protection trial, and a hint of something positive on an early repair trial. I'd also like to see lazybones Prof G working again and Prof M spending less time in the local boozer with MD2 – but I'm being greedy. Best wishes for 2015.

    • I hope you get your wishes but can I ask for more time in the local boozer with MD2 🙂

      We like to shoot the breeze and then every now and then, we haves some really good ideas.!

      The locusts and pot was not one of them.

  • HSCT is an area I'm watching with interest. In my view it is the best way to stop the disease in its tracks and I believe the cost would be offset in the long run when you consider the price of disability. Many people are now having the procedure aboard and it seems to be gaining momentum as a treatment option. I also understand its recently been approved in Norway for severe MS.

    • I think you are correct regarding the cost benefit compared to years of administering DMTs. The dosing schedule of Alemtuzumab would seem to make alot of sense. But I think that wealthy patients, such as Jack Osbourne, will choose stem cell therapies with the chance for "a cure" even though they do not have much disability.

    • There is HSCT and quack stem cell, please do not fall into the trap of thinking the quack stem cell clinics do anything than take your money. If HSCT is done properly is a very aggressive treatment and needs to be done in a very reputable place with bone fide experience. This can be a life threatening procedure.

      Also remember it is an extreme way of replacing the immune system and is not making nerves or myelin so the RRMS variant is going to respond the best.

  • HSCT is being done in Chicago for RRMS only. Many insurance companies are paying, including MediCARE! Join for more info.
    For SPMS & PPMS, search FB for Hematopoietic Stem Cell Transplant to find the worldwide FB group for more info.
    My husband had HSCT for RRMS in 2011 & it stopped progression of disease!! He's even had reversal of double vision, pain, numbness, heat sensitivity. It works! But don't fall for all the other stem cell scams out there. HSCT includes chemo, no chemo, no cure!

By Prof G



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