Autologous Hematopoietic Stem Cell Transplantation for Multiple Sclerosis in A Western Australian Cohort

OBJECTIVE: To review the outcome of AHSCT for multiple sclerosis in Western Australian cohort.BACKGROUND: Autologous hematopoietic stem cell transplantation (AHSCT) has shown promise as a treatment strategy for multiple sclerosis (MS), possibly by eradicating self-reactive immune cells and resetting of the immune repertoire upon post-transplant reconstitution. However, the precise mechanism is unclear and we undertook a detailed analysis of lymphocyte subsets following AHSCT for MS.METHODS: Fourteen patients with aggressive MS unresponsive to other therapies underwent AHSCT. Stem cell mobilization was with cyclophosphamide 2g/m2 and granulocyte-colony stimulating factor 5ug/kg bd. Conditioning chemotherapy was with cyclophosphamide 50mg/kg and rabbit antithymocyte globulin 1mg/kg days -5 to -2. Lymphocyte subsets including CD4, CD8, naive T-cells, recent thymic emigrants, T-regulatory cells, TH1, TH2 and TH17 cells were assessed by flow cytometry for 2 years following AHSCT. Eleven healthy volunteers were used as controls.RESULTS: In the first 2-years after AHSCT following intensive physiotherapy some patients noticed minor improvement in walking distance or bladder function. However, most patients remained stable with neither improvement nor deterioration and some patients reported worsening of the disease over a minimum 2-year interval. In the lymphocytes subsets, in the short term there was a clear shift in favour of CD8 cells and Th1 cells. Naive T-cells and RTEs fall initially but re-establish by 12 months. TH17 cells appear to emerge with time.CONCLUSIONS: In this group of patients with advanced MS, neurological function 24 months post-AHSCT was essentially stable in half the cohort while the remainder experienced clinical progression. Disclosure: Dr. Pedrini has nothing to disclose. Dr. Hall has nothing to disclose. Dr. Cull has nothing to disclose. Dr. Augustson has nothing to disclose. Dr. Walters has nothing to disclose. Dr. Crosbie has nothing to disclose. Dr. William M. Carroll has received personal compensation for activities with Schering, Novartis, Merck Serono, Sanofi, CSL, and Biogen-Idec as a speaker. Dr. Kermode has received personal compensation for activities with Bayer, BioCSL, Biogen, Genzyme, Innate Immunotherapeutics, Merck Serono, Novartis, Sanofi, Sanofi-Aventis, and Teva as speaker honoraria and as a member of the scientific advisory board.