Stem cell transplants may HALT multiple sclerosis

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Science Translational Medicine  21 Jan 2015:
Vol. 7, Issue 271, pp. 271ec13
DOI: 10.1126/scitranslmed.aaa6672

Multiple sclerosis (MS) is an autoimmune disease that affects over 2 million patients worldwide. The early stages of the disease are typified by relapsing-remitting phases of active central nervous system inflammation. This inflammation causes profound damage to the central nervous system, ultimately resulting in a secondary progressive phase accompanied by permanent disability. Frontline therapies currently include 10 anti-inflammatory drugs, many of which suppress measurable disease activity short-term. However, 60 to 80% of patients experience breakthrough disease after 2 years. Nash et al. report the 3-year interim results of a 5-year clinical trial designed to “reset” the patient’s own immune system using myeloablative high-dose immunosuppressive therapy combined with autologous hematopoietic cell transplantation.

This clinical trial, “Hematopoietic Stem Cell Transplantation for Relapsing-Remitting MS (HALT-MS),” enrolled MS patients in the early relapsing-remitting phase but who had demonstrated previous failure of frontline therapies to suppress active disease. CD34+ hematopoietic stem cells were mobilized and collected from peripheral blood. Twenty-four patients then underwent myeloablative high-dose immunosuppressive therapy followed by autologous hematopoietic stem cell transplantation—a procedure most typically used to treat hematopoietic malignancies. The authors’ major finding was that nearly 80% of patients were free of detectable disease activity after 3 years. Importantly, deep sequencing of the CD4+ T cell receptor repertoire revealed that the treatment resulted in a “reset” of T cell diversity in the patient’s immune system, potentially abrogating the autoimmune component of the disease.

The 3-year interim results of this clinical trial suggest that high-dose immunosuppressive therapy combined with autologous hematopoietic cell transplantation may provide an effective treatment option for select MS patients who have failed conventional therapy. It remains unclear if these short-term results will extrapolate to long-term remission of disease activity. Moreover, this treatment regimen carries risk of severe adverse events including death. Time will tell whether the long-term benefits of this therapy outweigh the risks for MS patients.

R. 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. 10.1001/jamaneurol.2014.3780 (2014). [Abstract]

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