Hematopoietic stem cell transplantation for multiple sclerosis

Hematopoietic stem cell transplantation (HSCT) was proposed as a treatment for multiple sclerosis (MS) in 1995 based on favorable results in animal models including experimental autoimmune encephalomyelitis. These initial or first-generation trials were developed by medical oncology subspecialists, used malignancy-specific myeloablative transplantation regimens, and selected patients with secondary progressive MS with rapid progression of disability. In general, these trials suffered from higher than anticipated toxic reactions including treatment-related and disease-related mortality, continued loss of brain volume as seen on magnetic resonance imaging (MRI), and, at least in some patients, continued progressive disability despite marked attenuation or absence of gadolinium-enhancing lesions on MRI. Learning from these experiences, second-generation transplantation trials for MS are using MS-specific nonmyeloablative transplantation regimens and selecting for active relapses despite the use of interferon treatment in patients with less accumulated disability. While still preliminary, results using second-generation nonmyeloablative HSCT regimens are encouraging with minimal treatment-related morbidity and improvement in Expanded Disability Status Scale (EDSS) scores. The following 3 variables seem important in predicting the benefit and minimizing the toxic effects from an autologous stem cell transplantation in patients with MS: the selection of patients who still have inflammatory disease (ie, gadolinium enhancement on MRI and/or frequent active relapses), treatment early in the course before the onset of significant irreversibly progressive disability, and the use of a safer lymphoablative but nonmyeloablative HSCT conditioning regimen.

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