ABSTRACT
BACKGROUND: Autologous hematopoietic stem cell transplantation (aHSCT) for treatment of multiple sclerosis (MS) is gaining increasing prominence in the therapeutic landscape. This review article focuses on describing the evidence and European guidelines for aHSCT so that neurologists in Germany can consider this treatment option for appropriate MS patients. In this context, it must be taken into consideration that in every case a cost transfer must be individually applied for. AIM: To provide information for neurologists considering aHSCT for patients with MS. MATERIAL AND METHODS: In this narrative review articles from PubMed were pooled and analyzed. RESULTS AND DISCUSSION: High quality data from randomized, controlled clinical trials are required to compare the efficacy of aHSCT to the currently available highly effective disease-modifying therapies (DMT) so that reliable conclusions can be drawn regarding the relationship between the risks and benefits of aHSCT in MS; however, the studies discussed in this review provide important points of reference for patient selection and the transplantation protocol. Further advice is available from the European Society for Blood and Marrow Transplantation (EBMT) for experienced centers considering aHSCT. The available data and the European guidelines suggest that patients aged less than 45 years, an expanded disability status scale (EDSS)â¯≤â¯5.5, highly active MS, a disease duration of less than 10 years, an ineffective course of DMT or rapidly progressive MS may be eligible for aHSCT and should be referred to an experienced center for further assessment.
Subject(s)
Hematopoietic Stem Cell Transplantation , Multiple Sclerosis, Chronic Progressive , Multiple Sclerosis , Hematopoietic Stem Cell Transplantation/methods , Humans , Multiple Sclerosis/diagnosis , Multiple Sclerosis/etiology , Multiple Sclerosis/therapy , Multiple Sclerosis, Chronic Progressive/etiology , Randomized Controlled Trials as Topic , Transplantation, Autologous/methods , Treatment OutcomeABSTRACT
Autologous haematopoietic stem cell transplantation (aHSCT) is gaining traction as a valuable treatment option for patients affected by severe multiple sclerosis (MS), particularly the relapsing-remitting form. We describe the current literature in terms of clinical trials, observational and retrospective studies, as well as immune reconstitution following transplantation, with a focus on the conditioning regimens used for transplantation. The evidence base predominantly consists of non-randomised, uncontrolled clinical trials or data from retrospective or observational cohorts, i.e. very few randomised or controlled trials. Most often, intermediate-intensity conditioning regimens are used, with promising results from both myeloablative and lymphoablative strategies, as well as from regimens that are low and high intensity. Efficacy of transplantation, which is likely secondary to immune reconstitution and restored immune tolerance, is, therefore, not clearly dependent on the intensity of the conditioning regimen. However, the conditioning regimen may well influence the immune response to transplantation. Heterogeneity of conditioning regimens among studies hinders synthesis of the articles assessing post-aHSCT immune system changes. Factors associated with better outcomes were lower Kurtzke Expanded Disability Status Scale, relapsing-remitting MS, younger age, and shorter disease duration at baseline, which supports the guidance for patient selection proposed by the European Society for Blood and Marrow Transplantation. Interestingly, promising outcomes were described for patients with secondary progressive MS by some studies, which may be worth taking into account when considering treatment options for patients with active, progressive disease. Of note, a significant proportion of patients develop autoimmune disease following transplantation, with alemtuzumab-containing regimens associated with the highest incidence.
