Hematopoietic stem cell transplantation for multiple sclerosis: collaboration of the CIBMTR and EBMT to facilitate international clinical studies

Abstract

Clinical investigation of autologous hematopoietic stem cell transplantation (HSCT) as therapy for multiple sclerosis (MS) has been ongoing for over a decade. While several phase II studies have been finalized or are in progress, no definitive prospective randomized studies comparing HSCT versus alternative therapies for MS have been completed. In this conference report of North American and European experts who are involved in the care of MS patients, including neurologists and HSCT physicians, and representatives of the Center for International Blood and Marrow Transplant Research (CIBMTR) and European Group for Blood and Marrow Transplantation (EBMT), we (1) critically review progress to date in HSCT for MS; (2) describe current registry based projects including long-term follow-up studies in HSCT for MS and harmonization of the MS disease-specific research forms that will be used in future by both databases; (3) discuss challenges in study design for a prospective randomized clinical trial of HSCT versus alternative therapy for MS such as feasibility, and the importance of multidisciplinary clinical teams, need for a large sample size and duration of observation required for outcomes assessment; and (4) address future directions in HSCT therapy for MS. To undertake a definitive multicenter clinical trial in autologous HSCT for MS, it will be important to begin well in advance to assemble the team, evaluate proposals for study design, and consider options for the infrastructure and logistical support that will be needed. International collaboration, including partnership with the CIBMTR and EBMT, may be desirable and may in fact be critical for successful completion of a definitive comparative study.

Figures

Figure 1. Possible Outcomes of Autologous HCT for MS

The objective of autologous HCT for MS is to reduce inflammation and progression of the disease for a prolonged period of time. Early MS, which has characteristic lesions that show active inflammation, has a chronic relapsing remitting course, and is followed by progressive disease in later years. There is growing evidence that the clinical effects of autologous HCT are not limited to transient immune suppression (top graph) but could be related to a “resetting” of the immune system. However, several years of long term follow up of patients transplanted for MS is needed to determine durability of remission from clinical disease activity. Immunologic mechanistic studies using patient samples and MRI studies to assess demyelination and re-myelination will also be needed to elucidate the mechanisms of HCT effects on MS.

Figure 2. Time Course of MS and Pre- and Post-HCT Events for MS Research Forms

The “MS Disease Specific Baseline Form” will be used to capture information about MS disease activity pre-HCT. Diagnostic information, as well as assessment of MS activity including EDSS, clinical relapses, and MRI findings during the 2 years prior to HCT is of particular interest. The same form will be used to record baseline assessments both prior to mobilization and after collection of the graft for autologous HCT, and prior to receiving the preparative regimen, for allogeneic HCT. The “MS Disease Specific Follow Up Form” will be used to capture post-HCT information. (See also Table 2).