Abstract
Hematopoietic stern cell transplantation. (HSCT) was proposed as a treatment for muliple sclerosis (MS) in 1905 based on favorable results in,ani,mal models including, experimental autoimmune encephalomyelitis. These initial or first-generation trials were developed by medical oncology subspecialists, used malignancy-specific my eloablative 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 A related and disease-related mortality, continued loss of brain volume as seen on magnetic resonance imagmg (MRI), and, at least in some patients, continued progressive disability despite marked attenuation or absences 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 re miens 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