Treatment of Severe Multiple Sclerosis (MS) with High Dose Immunosuppressive Therapy (HDIT) and Autologous Stem Cell Transplantation (SCT).

Objectives: To evaluate the safety and therapeutic efficacy of HDIT and autologous CD341-selected SCT for severe multiple sclerosis. Methods: Autologous peripheral blood stem cells (PBSC) were mobilized with G-CSF (16 mg/kg/day) and CD34 selected. HDIT consisted of total body irradiation (800 cGy), cyclophosphamide (120 mg/kg) and horse anti thymocyte globulin (ATG) (90 mg/kg). Eligibility required that patients have an EDSS from 5.0 to 8.0, and deterioration of one or more points over the previous year. Results: Twenty patients with secondary progressive (15), primary progressive (4), or relapsing-remitting (1) with a median age of 43 (range, 27–60) years were enrolled to the study. The median EDSS at HDIT was 7.0 (range, 5.0–8.0). The median follow-up has been 5 (range, 1–24) months. Patient 4 had an MS flare during administration of G-CSF for mobilization. Patient 9, the only patient who received rabbit ATG because of a positive skin test to horse ATG, developed an EBV-associated post-transplant lymphoproliferative disorder and died at day 53. Patient 16 had sustained fevers and had an increase in the baseline EDSS of 7.5 to 8.5 at 3 months. Thirteen patients were considered evaluable at 3 or more months after transplant. At last evaluation, 2 patients had an increase of EDSS of at least 0.5 points, 4 patients had a decrease in EDSS of at least 0.5 points and 7 patients have remained stable. Importantly, no new or enhancing lesions have been observed on MRI of the brain except for patient 4 with the flare of MS. Conclusions: Toxicities from HDIT to date have been manageable and transient. We have added prednisone to the mobilization regimen to prevent G-CSF related neurological toxicity and prohibited the use of rabbit ATG. Further follow-up is required to fully assess outcome.