Autologous hematopoietic stem cell transplant, also known as “stem cell therapy” or by the acronym aHSCT, is an emerging yet controversial treatment method for multiple sclerosis (MS).
How aHSCT works for treatment of multiple sclerosis
The first step in aHSCT for MS involves collecting stem cells extracted from the patient’s bone marrow, peripheral blood or umbilical cord blood. After the material is collected, the patient’s immune system is either partially or completely ablated (immunoablation), which means the immune system is significantly reduced or destroyed temporarily with combinations of chemotherapy, monoclonal antibodies, and anti-thymocyte globulin. Because multiple sclerosis is an autoimmune disease, immune system suppression is a key step to essentially “reprogramming” it to function properly.
After immunoablation is complete, the collected stem cells are then re-infused to reconstitute the immune system and re-activate it. The intended result of the therapy is to return the immune system to a functional state so that the body’s autoimmune attack on myelin is halted.
Clinical studies involving aHSCT for MS
Autologous hematopoietic stem cell transplantation, an experimental therapeutic approach for multiple sclerosis as well as other diseases, has been tested in clinical settings and reviewed by leading scientists. Below are consolidated reports on three prominent aHSCT studies.
The first study consists of a case series involving a mix of 151 participants with relapsing and progressive MS. All participants underwent the treatment at Northwestern University in Chicago from July 2003 to February 2014.
A significant proportion of the patients (63%) were treated off study protocol on a compassionate basis (having secondary progressive disease, an Expanded Disability Status Scale [EDSS] score of 6.0 or more, or a particularly disabling disease). The remaining 55 participants (37%) were treated on the study protocol and met the criteria. Criteria included relapsing-remitting MS, EDSS between 2.0 and 6.0, received treatment with at least one FDA-approved drug, and had at least two corticosteroid-treated relapses within the last year or one corticoid treated relapse and gadolinium enhancing lesions shown on an MRI.
A relatively low proportion of treatment-related complications (9%) occurred and no deaths were reported. There was significant improvement in the EDSS for the majority of patients, which was the primary objective of the study, and 80% of the participants achieved disease-free survival at two years after treatment.
Another study, HALT-MS, was a single arm, Phase 2 trial of immunoablation followed by autologous transplantation of stem cells. The study included 25 participants (with relapsing-remitting MS, EDSS score between 3.0 and 5.5 and two or more clinical relapses in 18 months despite other treatment). The primary objective was noted time until treatment failed. After two and three years of treatment, the overall event-free survival probability was 83% and 78%, respectively. The EDSS score improved a median of 0.5 after three years.
The third study was a single arm, Phase 2 of immunoablation followed by autologous transplantation of stem cells across three Canadian Hospitals (NCT01099930). The study included 24 participants with aggressive MS. All had multiple early relapses, an EDSS score of at least 3.0 with five years of diagnosis, and evidence of ongoing clinical disease activity despite at least one year of treatment.
All 23 surviving participants were free of clinical relapses and new gadolinium enhancing lesions for the duration of follow-up (median 6.7 years).
Seventeen participants (70%) had no more progression in EDSS scores after treatment and eight patients (35%) had sustained improvement in EDSS scores three years after treatment. The rate of brain atrophy was not substantially different from healthy volunteers.
The three studies offer several positive results for continued investment in the role of aHSCT for MS patients.
More recent studies in aHSCT indicate that the therapy might be more successful if done in the earlier inflammatory stages of MS. Ideal candidates may be patients less than 40 years old with a short disease duration of less than five years, recurring and disabling relapses, presence of inflammatory activity shown on brain MRI scans, and who were unresponsive to approved therapies.
However, a large, randomized clinical study comparing aHSCTs with the best approved therapies is still needed to confirm the role of stem cell transplant in MS management.
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