Autologous stem cell transplantation in progressive multiple sclerosis - An interim analysis of efficacy

Based on the good results of experimental transplantation in animal models of multiple sclerosis and of other autoimmune diseases. we have treated 24 patients suffering from chronic progressive multiple sclerosis with high-do se chemotherapy (BEAM regimen) followed by autologous blood stem cell rescu e and antithymocyte globulin. Blood stem cells were mobilised with cyclopho sphamide at 4g/m(2) and G- (or GM-) CSF. In 9 cases, additional CD34(+) cel l-selection of the graft was performed. Hen we update previously published results of this novel treatment, mainly with regard to clinical efficacy, a s the median follow-up time has reached 40 months (range, 21-51). Infection s were the principal toxicity early after the procedure, with death of a pa tient from aspergillosis 65 days post stem cell infusion. No serious late e vents occurred apart from a case of autoimmune thyroiditis that developed 1 1 months after transplant in a patient who had received a CD34(+) cell-depl eted graft. Mild and transient neurotoxicity was observed in 10 patients (4 2%), most probably associated with fever and infections. Eighteen patients (18/23; 78%) responded to the treatment. i.e., they were improved or stabil ized, while live patients progressed, of which 4 had primary progressive di sease. Of those improved or stabilised (18), 9 patients have maintained sta ble condition whereas 9 developed relapses or they slowly resumed progressi on, although their disability scores have not gotten worse than they were b efore transplantation. The probability of progression-free survival (compar ed to entry status) at 3 years is 92% for patients with secondary progressi ve disease and 39% for the primary progressive type. CD34(+) cell-selection did not seem to yield better results except for a delay in progression or in relapse after transplantation. These results appear better than those ac hieved by any other treatment of progressive multiple sclerosis, including beta-interferon, but they need to be confirmed by other open or controlled studies in view of the well-known difficulty of judging objectively the eff ect of a treatment in patients with this disease.