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Stem Cells May Halt Progression of Multiple Sclerosis

By: Nehali Parikh, PharmD Candidate c/o 2016

Multiple sclerosis (MS) is an autoimmune disease that results in interrupted neurotransmission throughout the body. It occurs when the immune system mistakenly attacks myelin, the insulating layer surrounding nerve cells, causing the formation of scar tissue, called sclerosis. Fatigue, numbness, tingling, difficulty in walking, and dizziness are all common symptoms of MS.1

While there are various stages and forms of MS, relapsing-remitting MS (RRMS) is the most common form, in which mild or no symptoms occur within certain periods of more severe symptoms.3 MS is not a curable disease, but there are certain medications that have been approved to help treat relapsing forms of MS. These immunosuppressant agents aim to modify the disease course by treating exacerbations and alleviating symptoms.1

A non-randomized, multicenter clinical trial was conducted by the National Institute of Allergy and Infectious Diseases (NIAID)-funded Immune Tolerance Network, in which participants with RRMS received autologous stem cell transplants after treatment with a high dose of immunosuppressive therapy. The clinical trial, known as HALT-MS, is a prospective, open-label, single-arm, phase 2 clinical trial.5 The primary endpoint of this study is the time to treatment failure within 5 years after HCT, which is defined as death or disability by: change in EDSS score of more than 0.5 points compared to baseline, relapse or recurring symptoms lasting more than 48 hours, and 2 or more MS disease- related lesions on brain MRI that occurred 1 year or more after HCT.5

These participants were patients who experienced relapses with loss of neurologic function while they received disease-modifying therapies during 18 months prior to enrollment, including interferon beta-1a, glatiramer acetate, mitoxantrone, natalizumab, interferon beta-1b, methylprednisolone or dexamethasone, cyclophosphamide, methotrexate, minocycline, and plasma exchange. 5 Thirty-six patients with RRMS were screened and 25 were enrolled in this study.5

Eligible patients were aged 18 to 60 years and had a diagnosis of MS according to the McDonald criteria with: RRMS, Krutzke Expanded Disability Status Scale (EDSS) scores between 3.0 to 5.5, lesions that were shown on a brain MRI, duration of the disease for less than 15 years, and failure of disease modifying therapies. The failure of previous treatment was defined as 2 or more clinical relapses during 18 months of therapy that were shown with an increase in the EDSS score.5

In this trial, patients were initially given 1 mg/kg of prednisone for 10 days, which was completed 1 day before filgrastim therapy was initiated, in order to prevent MS relapse. Peripheral blood stem cells were collected from patients and treated with filgrastim for four days; CD34 cells were selected and cryopreserved. 5 Patients then received high dose chemotherapy, which was composed of 300 mg/m2 of carmustine on day -6, 200 mg/m2 of etoposide, 200 mg/m2 of cytarabine daily from days -5 to -2, and 140 mg/m2 of melphalan was on day-1. 5 Rabbit antithymocyte globulin, 2.5 mg/kg/d, was given on days -2 and -1. On day 0, CD34+ cells were thawed and infused in the patients. Filgrastim was administered from day 5 until the neutrophil count was greater than 500/µL. 5 Prednisone 0.5 mg/kg/d was given to patients on days 7 to 21 to prevent engraftment syndrome, then tapered over the following two weeks.

A three-year interim analysis of this five year trial   showed how high-dose immunosuppressive therapy with autologous hematopoietic cell transplant (HDIT/HCT) might lead to a sustained remission of RRMS.2 The disease activity was controlled, according to the primary endpoint criteria, through three years after HCT in most patients except in two patients, who had a failure of treatment.5

Previous clinical trials revealed that HDIT/HCT treatment was not effective in participants who had progressive MS. However, this data shows that it may be effective in participants who are in the early stages of RRMS. In fact, three years after the HDIT/HCT clinical trial, about 80% of the patients survived without experiencing any symptoms of MS, including any neurological disabilities.2, 3 during these three years of the trial, the investigators did not find many unexpected side effects. Most of the side effects that participants experienced were gastrointestinal as well as infections, both of which are common adverse effects of high dose immunosuppression.4

Daniel Rotrosen, MD, director of the NIAID Division of Allergy, Immunology and Transplantation, states, “Participants did not receive any MS drugs after transplant, yet most remained in remission after three years. In contrast, other studies have shown that the best alternative MS treatments induce much shorter remissions and require long-term use of immunosuppressive drugs that can cause serious side effects.”4

The researchers plan to follow the participants for a total of 5 years. The results from this will help determine what further studies need to be done to use HDIT/HCT as an effective alternative treatment in patients with MS.


  1. What is MS? National Multiple Sclerosis Society. Available at: http://www.nationalmssociety.org/What-is-MS/Definition-of-MS. Accessed 03/05/2015.
  2. Stem cells may halt progression of multiple sclerosis. NIH. Available at: http://www.nih.gov/news/health/dec2014/niaid-29.htm. Published 12/29/2014. Accessed 03/05/2015.
  3. Immune system reset may halt multiple sclerosis progression. NIH. Available at: http://www.nih.gov/researchmatters/january2015/01122015reset.htm. Accessed 03/06/2015.
  4. Stem cells may halt progression of multiple sclerosis. Pharmacy Practice News. Available at: http://www.pharmacypracticenews.com/ViewArticle.aspx?d=Web%2bExclusives&d_id=239&i=January+2015&i_id=1141&a_id=2913. Accessed 03/04/2015.
  5. Nash RA, Hutton GJ, Racke MK, 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. 2015;72(2):159-169.

[pubmed_related keyword1=”multiple” keyword2=”sclerosis” keyword3=”stem”]

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