Haematopoietic Stem Cell Transplantation for the Treatment of Multiple Sclerosis: Recent Advances

Abstract

Purpose of review: Autologous haematopoietic stem cell transplantation (AHSCT) is increasingly considered a treatment option for patients with multiple sclerosis (MS), an autoimmune demyelinating and degenerative disease of the central nervous system (CNS). AHSCT persistently suppresses inflammation and improves the disease course in large proportions of patients with relapsing-remitting (RR) MS. Aim of this article is to review the relevant new knowledge published during the last 3 years.

Recent findings: Laboratory studies reported confirmatory and new insights into the immunological and biomarker effects of AHSCT. Retrospective clinical studies confirmed excellent outcomes in RRMS, showing possible superior effectiveness over standard therapies and suggesting a possible benefit in early secondary progressive (SP) MS with inflammatory features. New data on risks of infertility and secondary autoimmunity were also reported. Further evidence on the high effectiveness and acceptable safety of AHSCT strengthens its position as a clinical option for aggressive RRMS. Further research is needed to better define its role in treatment-naïve and progressive forms of MS, ideally within randomised clinical trials (RCTs).

Keywords: Alemtuzumab; Biomarker; Haematopoietic stem cell transplantation; Multiple sclerosis; Reconstitution.

Fig. 1

Immune reconstitution after HSCT. A T cell dynamics. T cell numbers reconstituted slowly and remained under the baseline during follow-up. Different stages of T cell differentiation were defined by CCR7 and CD45RA expression. Naive (N) T cells recovered slowly by thymus-dependent reconstitution only after 6 months post HSCT. Effector memory (EM) T cells increased rapidly after HSCT stimulated by lymphopenia-induced proliferation (LIP) and antigen responses and remained above the baseline during the period study. Most of the EM differentiated from central memory (CM) T cells resistant to high-dose chemotherapy treatment. The persistent EM proliferated less than newly emerging T cells and differentiated in terminally differentiated memory cells (EMRA) with senescent and exhausted phenotype (S) (CD57 + , CD27 − , CD28 − , PD1 +) with reduced proinflammatory potential. Naïve T cells eventually differentiated in EM and CM with new TCR repertoire. B B cell dynamics. B cells were depleted by anti-CD20 treatment before HSCT. The subsets of B cells were defined by the expression of CD24, CD24 and CD38. Substantial proportion of early B cells post-HSCT was plasma cells (PCs). Transitional B cells (T) increased at 1 months after HSCT and decreased in the following months, while mature B cells rose and remained higher during the period study. Memory B cells generated slowly and remained below the baseline at 1-year follow-up. C Dynamics of NK and innate-like T cells including $\gamma \delta$ T cells, mucosal-associated invariant T (MAIT) and NK(-like) T cells. NK and innate-like T cell subsets were identified by the expression of CD56, CD3 $\gamma \delta$ /$\alpha \beta$/Va7.2 TCR, CD161 and IL18R. NK cells include 2 subsets CD56^bright with immunoregulatory functions and CD56^dim with high cytotoxic functions. CD56^bright cells increased after HSCT, while CD56^dim increased after 1 month and declined to recovery slowly during the 2-year follow-up. MAIT, $\gamma \delta$ T and NK(-like) T cells decreased after HSCT and remained below the baseline