1.
Autologous hematopoietic cell transplantation for treatment-refractory relapsing multiple sclerosis: Position statement from the american society for blood and marrow transplantation
Cohen JA, Baldassari LE, Atkins HL, Bowen JD, Bredeson C, Carpenter PA, Corboy JR, Freedman MS, Griffith LM, Lowsky R, et al
Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation. 2019
Abstract
Multiple sclerosis (MS) is a chronic, disabling, immune-mediated, central nervous system demyelinating and degenerative disease. Approved disease modifying therapies may be incompletely effective in some patients with highly active relapsing disease and high risk of disability. Immunoablative or myeloablative therapy followed by autologous hematopoietic cell transplantation (AHCT) has been investigated in retrospective studies, clinical trials, and meta-analyses/systematic reviews as an approach to address this unmet clinical need. On behalf of the American Society for Blood and Bone Marrow Transplantation (ASBMT), a panel of experts in AHCT and MS convened to review available evidence and make recommendations on MS as an indication for AHCT. Review of recent literature identified eight retrospective studies, eight clinical trials, and three meta-analyses/systematic reviews. In aggregate, these studies indicate that AHCT is an efficacious and safe treatment for active relapsing forms of MS to prevent clinical relapses, MRI lesion activity, and disability worsening, and to reverse disability, without unexpected adverse events. Based on the available evidence, the ASBMT recommends that treatment-refractory relapsing MS with high risk of future disability be considered a "standard of care, clinical evidence available" indication for AHCT. Collaboration of neurologists with expertise in treating MS and transplant physicians with experience performing AHCT for autoimmune disease is crucial for appropriate patient selection and optimizing transplant procedures to improve patient outcomes. Transplant centers in the United States and Canada are strongly encouraged to report baseline and outcomes data on patients receiving AHCT for multiple sclerosis to the Center for International Blood and Marrow Transplant Research.
2.
Intravenous immunoglobulin in relapsing-remitting multiple sclerosis: a dose-finding trial
Fazekas F, Lublin FD, Li D, Freedman MS, Hartung HP, Rieckmann P, Sørensen PS, Maas-Enriquez M, Sommerauer B, Hanna K, et al
Neurology. 2008;71((4):):265-71.
Abstract
OBJECTIVE Several studies have reported a reduction of relapses after the long-term administration of IV immunoglobulin (IVIG) to patients with relapsing-remitting multiple sclerosis (RRMS), but they were mostly small and differed in terms of predefined outcome variables and treatment regimen. We therefore set out to test two different doses of a new formulation of immunoglobulin termed IGIV-C 10% for suppression of both clinical and MRI disease activity as well as safety. METHODS One hundred twenty-seven patients with RRMS participated in this multicenter, randomized, double-blind, placebo-controlled trial. Forty-four and 42 patients received treatment with 0. 2 and 0. 4 g/kg of IGIV-C 10%, and 41 patients received an equal volume of placebo (0. 1% albumin) every 4 weeks for 48 weeks. The primary endpoint was the proportion of relapse-free patients. The main secondary endpoint was lesion activity assessed by 6-weekly MRI. RESULTS Baseline variables were similar in IVIG- and placebo-treated groups. After 1 year, the proportion of relapse-free patients did not differ statistically according to treatment (IVIG 0. 2 g/kg: 57%; IVIG 0. 4 g/kg: 60%; placebo: 68%), and there was no difference regarding the cumulative number of unique newly active MRI lesions (median numbers: IVIG 0. 2 g/kg: 8. 0; IVIG 0. 4 g/kg: 5. 0; placebo: 7. 2) after 48 weeks. There were no significant between-group differences in the rates of adverse events. CONCLUSION Although IV immunoglobulin (IVIG) treatment was well tolerated, this study did not substantiate a beneficial effect of IVIG in doses ranging from 0. 2 to 0. 4 g/kg. This result seriously questions the utility of IVIG for the treatment of relapsing-remitting multiple sclerosis.