A prospective, randomized, controlled trial of autologous haematopoietic stem cell transplantation for aggressive multiple sclerosis: a position paper

Abstract

Background:Haematopoietic stem cell transplantation (HSCT) has been tried in the last 15 years as a therapeutic option in patients with poor-prognosis autoimmune disease who do not respond to conventional treatments. Worldwide, more than 600 patients with multiple sclerosis (MS) have been treated with HSCT, most of them having been recruited in small, single-centre, phase 1–2 uncontrolled trials. Clinical and magnetic resonance imaging outcomes from case series reports or Registry-based analyses suggest that a major response is achieved in most patients; quality and duration of response are better in patients transplanted during the relapsing–remitting phase than in those in the secondary progressive stage.Objectives:An interdisciplinary group of neurologists and haematologists has been formed, following two international meetings supported by the European and American Blood and Marrow Transplantation Societies, for the purpose of discussing a controlled clinical trial, to be designed within the new scenarios of evolving MS treatments.Conclusions:Objectives of the trial, patient selection, transplant technology and outcome assessment were extensively discussed. The outcome of this process is summarized in the present paper, with the goal of establishing the background and advancing the development of a prospective, randomized, controlled multicentre trial to assess the clinical efficacy of HSCT for the treatment of highly active MS.

Hematopoietic Stem Cell Therapy for Multiple Sclerosis: Top 10 Lessons Learned

“…A recently initiated joint EBMT and CIBMTR registry-based [55], long-term follow-up study [56] and a proposed phase III randomized trial of stem cell transplants versus the best available therapy for patients with highly active MS who have failed interferon-β therapy [57] will provide further information regarding the role of HSCT in MS.…”

“…Could HSCT provide better outcomes in this group of patients compared to current or new immunosuppressive agents, especially with the increasing risk of toxicity with long-term use of newer agents? A proposed international multicenter, collaborative, randomized clinical trial of HSCT compared to the best standard-of-care treatment will improve the understanding of the role that HSCT should play in the management of MS [57]. In addition, clinical experience using HSCT for patients with other CNS autoimmune demyelinating diseases (e.g., neuromyelitis optica) has just starting to be documented [70,71].…”

Autologous hematopoietic SCT normalizes miR-16, -155 and -142-3p expression in multiple sclerosis patients

“…22 In our study, we demonstrate, for the first time, that AHSCT promotes persistent downregulation of disease-related miRs, while increasing the expression of their predicted target genes. Moreover, we detected increased Treg counts, with higher expression of immunoregulatory molecules.…”

Stem cells: Stemming the tide

“…In 2012, Freedman and his colleagues planned a 114 patient, controlled phase III trial of aHSCT, in which control patients would be randomized to the best available therapy initially and then crossed over onto aHSCT only when their disease progresses 5 . But funding for the trial has remained elusive, and recruitment might also be problematic because people in the control group might drop out to explore other experimental options.…”