Functional Stabilization of Worsening Multiple Sclerosis Patients Treated with High Dose Immunosuppression and Stem Cell Rescue.

Objective: To test the hypothesis that intense immunosuppression could prevent the progression of sever multiple sclerosis (MS) refractory to conventional medications Design: Phas I and II clinical trial. Setting: Transplant centers at several US medical centers. Participants: 26 relapsing or remitting secondary progressive or primary progressive MS patients, ages 18 to 60 years,who had failed conventional medications (interferon beta-1a [Avonex, Betaseron], glatiramer [Copaxone], methotrexate, cyclophosphamide,azothiaprine, steroids, intravenous immunoglobin), andhwo had progressed at least 1 Kurtzke Expanded Disability Status Scale (EDSS) point over that from the previous 12 months. Interventions: Granulocyte colony-stimulating factor (G-CSF) was given to the patients, followed by harvest of blood stem cells. Stem cells were then frozen at -180ºC. Following this, high-dose total body irradiation, cyclophosphamide, and anti-thymocytic globulin (HDIT) were given to suppress immune function. Finally, the stem cells were transplanted back (SCT) to reconstitute naïve immune systems. Main Outcome Measures: EDSS, Scripps Neurological Rating Scale, Amulation Index, 9-Hole Peg Test, Paced Auditory Serial Addition Test (PASAT), and magnetic resonance imaging (MRI) of brain. Results: With a mean follow-up period of 15.1 months (range 6-45 months), we found the following: on the EDSS, 77% were stable or showed slight improvement. There was no change in median Ambulation Index score (n=9) or in median Scripps rating (n=20). On the 9-Hole Peg Test (n=17), 53% were stable or improved; on the PASAT (n=13); 70% were stable or improved. For MRI(n=26); only 4 subjects had enhancement on posttreatment images. For adverse events, there was 1 death and several manageable transplant-related disorders. Conclusion: HDIT and SCT appear to stabilize the majority of severe MS patients who have failed conventional treatments. Further follow-up and phase III trial will be done.