Autologous haematopoietic stem cell transplantation for treatment of multiple sclerosis

Abstract

Autologous haematopoietic stem cell transplantation (AHSCT) is a multistep procedure that enables destruction of the immune system and its reconstitution from haematopoietic stem cells. Originally developed for the treatment of haematological malignancies, the procedure has been adapted for the treatment of severe immune-mediated disorders. Results from ~20 years of research make a compelling case for selective use of AHSCT in patients with highly active multiple sclerosis (MS), and for controlled trials. Immunological studies support the notion that AHSCT causes qualitative immune resetting, and have provided insight into the mechanisms that might underlie the powerful treatment effects that last well beyond recovery of immune cell numbers. Indeed, studies have demonstrated that AHSCT can entirely suppress MS disease activity for 4–5 years in 70–80% of patients, a rate that is higher than those achieved with any other therapies for MS. Treatment-related mortality, which was 3.6% in studies before 2005, has decreased to 0.3% in studies since 2005. Current evidence indicates that the patients who are most likely to benefit from and tolerate AHSCT are young, ambulatory and have inflammatory MS activity. Clinical trials are required to rigorously test the efficacy, safety and cost-effectiveness of AHSCT against highly active MS drugs

Profound but Transient Changes in the Inflammatory Milieu of the Blood During Autologous Hematopoietic Stem Cell Transplantation

“…Autologous hematopoietic stem cell transplantation (AHSCT) is a well-proven treatment used predominantly for blood malignancies, but also for solid tumors and inflammatory diseases such as multiple sclerosis (MS) and systemic sclerosis [1][2][3]. Although the removal of malignant cells is assumed to be a key aspect in the treatment of lymphomas and myelomas, less is known about the mechanisms behind the improvements seen in patients with inflammatory diseases.…”

Prospective phase II clinical trial of autologous haematopoietic stem cell transplant for treatment refractory multiple sclerosis

“…The rationale behind AHSCT is that high dose chemotherapy may eradicate autoreactive lymphocyte clones while the infusion of haematopoietic stem cells may reconstitute a tolerant immune system, possibly by renewed thymic output 16. Immune reconstitution (IR) of patients with MS post-AHSCT suggests that transplantation removes putative proinflammatory lymphocytes such as mucosal-associated invariant T (MAIT) cells17 while regenerating immunoregulatory populations such as CD39 + T regulatory cells,18 CD56 high natural killer (NK) cells19 and suppressor CD8 + CD57 + T cells,17 some of which are recognised to be dysfunctional in MS 18.…”

Immune rebound associates with a favorable clinical response to autologous HSCT in systemic sclerosis patients

“…56 In this scenario, studies have shown that donor-derived Bregs are important for suppression of murine sclerodermatous chronic graft-versus-host disease. 72 In the present study, we found a correlation between favorable clinical outcomes and Breg levels after AHSCT in SSc patients.…”