June 1, 2009 (Atlanta, Georgia) — An ongoing phase 2 trial of high-dose immunosuppressive treatment (HDIT) and autologous hematopoietic stem-cell transplantation (AHSCT) in aggressive relapsing remitting multiple sclerosis (RRMS) (HALT-MS) has shown encouraging preliminary results.
The findings were presented here at the Consortium of Multiple Sclerosis Centers (CMSC) 23rd Annual Meeting by George Hutton, MD, from Baylor College of Medicine, in Houston, Texas, and colleagues.
The study was designed to determine whether HDIT/AHSCT could result in sustained remissions and prevent decline of neurologic function in patients with active RRMS.
Previous small studies using this approach have shown that approximately 70% of treated patients do not show disease progression after at least 3 years, with the greatest efficacy observed when the approached was used in patients with earlier- rather than later-stage disease.
"The ultimate goal of this approach is to reset the immune system to halt the autoimmune attack in MS," Dr. Hutton told Medscape Neurology & Neurosurgery. "In previous trials, those patients with relapsing forms of MS, especially those with Expanded Disability Status Scale [EDSS] scores < 6.0, have fared better," he said. "In HALT-MS, we are attempting to identify MS patients with relatively early relapsing disease who have not responded favorably to traditional immunomodulatory or immunosuppressive treatments."
Dr. Hutton presented preliminary results on the first 10 patients, with median follow-up of 12.2 months (range, 0 – 27). The trial has a planned enrollment of 25 patients with 5-year follow-up. Patients were aged 18 to 60 years and had a poor response to standard disease-modifying therapy with residual disability. The duration of MS was less than 15 years. Patients' EDSS score was between 3.0 and 5.5, and to be included, they had to have had at least 1 relapse within the past 18 months.
The researchers found no clinical relapses after HDIT/AHSCT, and no patient required disease-modifying treatment. At baseline, a total of 38 gadolinium-enhancing lesions on brain magnetic resonance imaging (MRI) were noted among the participants, and no new lesions were observed in any patients after up to 13 months of study treatment. Patients showed up to a 2.5-point improvement in EDSS with treatment.
"Observed adverse events were transient and mild," Dr. Hutton said during his presentation. One patient developed pseudo graft-vs-host disease, 1 patient developed pseudo relapse, and 1 patient developed methicillin-resistant Staphylococcus aureus infection.
"HDIT followed by AHSCT can be performed safely in patients with treatment-refractory MS, and these initial results are encouraging," he said.
According to Dr. Hutton, to explore the mechanism of action, extensive immunologic studies will be examining cell type, thymic function, T-cell and B-cell responses to myelin, and other parameters after AHSCT.
"We have previously shown that the T-cell repertoire is changed for up to 2 years after AHSCT in MS patients to show more naive CD4+ T cells and fewer T memory cells, and we hope to see such results as long as 5 years posttransplant in HALT-MS," he said.
"Although further studies are needed, this approach is interesting," said Stuart D. Cook, MD, professor in the department of neurology and neuroscience at the University of Medicine and Dentistry, in Newark, New Jersey, who attended the presentation.
"A question about this approach is whether it is just the intense immunosuppression alone that's causing the improvement and whether or not the autologous transplant is necessary," Dr. Cook told Medscape Neurology & Neurosurgery.
"The ideal design would have been to have 1 group that got the intense immunosuppressive chemotherapy plus placebo and the other group the intense immunosuppressive chemotherapy with the stem cells to see whether the transplant added benefit," Dr. Cook said. "Intense chemotherapy can often result in stabilization for 3 to 4 years by itself," he added.
The study was supported by the Immune Tolerance Network and National Institute of Allergy and Infectious Diseases. Dr. Hutton reports no relevant funding disclosures.
The Consortium of Multiple Sclerosis Centers (CMSC) 23rd Annual Meeting and 2nd joint meeting of the American Committee for Treatment and Research in MS (ACTRIMS): Abstract P08. Presented May 29, 2009.
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Cite this: High-Dose Immunosuppression and Stem-Cell Transplantation Show Activity in Early RRMS - Medscape - Jun 01, 2009.