Long-term Outcomes After Autologous Hematopoietic Stem Cell Transplantation for Multiple Sclerosis.

IMPORTANCE: Autologous hematopoietic stem cell transplantation (AHSCT) may be effective in aggressive forms of multiple sclerosis (MS) that fail to respond to standard therapies. OBJECTIVE: To evaluate the long-term outcomes in patients who underwent AHSCT for the treatment of MS in a large multicenter cohort. DESIGN, SETTING, AND PARTICIPANTS: Data were obtained in a multicenter, observational, retrospective cohort study. Eligibility criteria were receipt of AHSCT for the treatment of MS between January 1995 and December 2006 and the availability of a prespecified minimum data set comprising the disease subtype at baseline; the Expanded Disability Status Scale (EDSS) score at baseline; information on the administered conditioning regimen and graft manipulation; and at least 1 follow-up visit or report after transplant. The last patient visit was on July 1, 2012. To avoid bias, all eligible patients were included in the analysis regardless of their duration of follow-up. Data analysis was conducted from September 1, 2014 to April 27, 2015. EXPOSURES: Demographic, disease-related, and treatment-related exposures were considered variables of interest, including age, disease subtype, baseline EDSS score, number of previous disease-modifying treatments, and intensity of the conditioning regimen. MAIN OUTCOMES AND MEASURES: The primary outcomes were MS progression-free survival and overall survival. The probabilities of progression-free survival and overall survival were calculated using Kaplan-Meier survival curves and multivariable Cox proportional hazards regression analysis models. RESULTS: Valid data were obtained from 25 centers in 13 countries for 281 evaluable patients, with median follow-up of 6.6 years (range, 0.2-16 years). Seventy-eight percent (218 of 281) of patients had progressive forms of MS. The median EDSS score before mobilization of peripheral blood stem cells was 6.5 (range, 1.5-9). Eight deaths (2.8%; 95% CI, 1.0%-4.9%) were reported within 100 days of transplant and were considered transplant-related mortality. The 5-year probability of progression-free survival as assessed by the EDSS score was 46% (95% CI, 42%-54%), and overall survival was 93% (95% CI, 89%-96%) at 5 years. Factors associated with neurological progression after transplant were older age (hazard ratio [HR], 1.03; 95% CI, 1.00-1.05), progressive vs relapsing form of MS (HR, 2.33; 95% CI, 1.27-4.28), and more than 2 previous disease-modifying therapies (HR, 1.65; 95% CI, 1.10-2.47). Higher baseline EDSS score was associated with worse overall survival (HR, 2.03; 95% CI, 1.40-2.95). CONCLUSIONS AND RELEVANCE: In this observational study of patients with MS treated with AHSCT, almost half of them remained free from neurological progression for 5 years after transplant. Younger age, relapsing form of MS, fewer prior immunotherapies, and lower baseline EDSS score were factors associated with better outcomes. The results support the rationale for further randomized clinical trials of AHSCT for the treatment of MS.

Disobedience and driving in patients with epilepsy in Greece.

OBJECTIVE: Regulations and guidelines regarding driving privileges of patients with epilepsy vary greatly worldwide. The aim of our study was twofold: firstly, to evaluate disobedient drivers in Greece and to elucidate their awareness of the law, emotional responses, and seizure profile and, secondly, to identify determinants of disobedience regarding driving among patients with epilepsy. METHODS: All consecutive patients with epilepsy who visited the epilepsy outpatient clinic of two tertiary epilepsy centers were invited to participate in the study. One hundred ninety patients met our inclusion criteria. RESULTS: Fifty-two percent of our study population was aware of the driving restrictions. More than one out of three patients were disobedient (35.8%). Being a male was associated with a 6.07-fold increase in the odds of being disobedient (95% CI: 2.73-13.47, p < 0.001); being employed was associated with a 4.62-fold increase in the odds of being disobedient (95% CI: 2.20-9.68, p < 0.001); and each extra antiepileptic drug (AED) was associated with a decrease in the odds of disobedience by a factor of 0.41 (95% CI: 0.26-0.63, p < 0.001). CONCLUSION: Male gender, employment, and number of AEDs are important determinants of disobedience regarding driving among patients with epilepsy.

Stem cell transplantation for multiple sclerosis: what is the evidence?

Experimental and clinical observations have indicated that high-dose immunosuppression followed by autologous stem cell transplantation (ASCT) can induce remissions in severe, refractory, autoimmune diseases including multiple sclerosis (MS), a T cell-mediated autoimmune disorder against CNS myelin components, causing severe chronic disability. Control of the disease is unsatisfactory in most of the patients, especially those with rapidly evolving relapsing-remitting course and those with chronic progressive disease. The rationale for treating autoimmune diseases with ASCT is based on the immunosuppressive and immunomodulating effects of ASCT which may shift the immunological balance towards disease quiescence, a hypothesis supported by the results of ASCT in animal models of MS and by clinical observations in MS patients transplanted for concurrent malignancies. A number of phase I-II studies of ASCT in patients with active MS, conducted worldwide since 1995, and a comprehensive analysis of 85 patients, recently reported by the European Group for Blood and Marrow Transplantation (EBMT), have shown the feasibility of the method, a prominent anti-inflammatory effect on magnetic resonance imaging (MRI) disease, and a possible clinical benefit for active and refractory cases. The impact on MRI disease parameters appears superior with ASCT than with conventional therapies but the clinical results, in terms of stabilization of disease and prevention of disability, need to be validated in prospective, controlled trials. The procedure is also associated with a transplant-related mortality risk, of about 5% in high-risk cases, i.e., in older patients, those with high disability scores, those receiving strong myeloablative conditioning regimens and those undergoing intensive in vivo or ex vivo T cell-depletion. Therefore, it could be recommended for the treatment of a chronic, non-lethal, disease like MS only if it proved superior to standard therapies. A randomized trial is now launched by the EBMT to compare ASCT to mitoxantrone, currently regarded as one of the best available treatments, in properly selected patients having high chance of response at minimal mortality risk.