The presentation will begin with a general overview of Multiple Sclerosis (MS): a chronic inflammatory, demyelinating disease, characterized as a relapsing, and often eventually progressive focal disorder of the white matter of the central nervous system (CNS), having the plaque as its hallmark. MS has a global prevalence of 33/100,000, unevenly distributed throughout the world, and it is the most common cause of non-traumatic disability in young adults.
Many drugs are available to treat the disease. Beside traditional drugs such as corticosteroids, azathioprine and cyclophosphamide, the advent of mid-90s "disease modifying drugs" (DMDs) has improved the natural course of the disease, leading to a better control.
The focus of the presentation is on the application of autologous transplantation (AHSCT) to MS. Different conditioning regimen available (low, intermediate, and high intensity) will also be described, as well as the mechanism of action of the procedure: in brief, following reconstitution of most major lineages of hematopoietic cells in the first months post-AHSCT, the T cell compartment is characterized initially by a transient homeostatic expansion of CD8+ memory T cells with an exhausted phenotype and potentially suppressive function, and subsequently reactivation of thymic function and gradual selection of CD4+ and CD8+ naive T cells over at least 2 years post- AHSCTs. The emerging T cell repertoire shows higher TCR diversity and qualitative exchange in that newly selected CD4+ T cells express different TCRs than prior to transplant, while some CD8+ clonotypes remain. Treg numbers and function increase, and consistent with this, pro- inflammatory miRNA expression together with profiles of gene expression normalize. Evidence shows that the greater benefits from AHSCT are for those patients that are still in an inflammatory course of the disease.
Clinical outcome of the procedure and benefits will also be discussed: DMDs are very effective, but relapses may occur even under natalizumab or alentuzumab, with accumulation of disability and incomplete recovery between two episodes. Furthermore, these treatments require multiple administrations or periodic infusions to maintain the beneficial effect. No treatment is currently capable of arresting or preventing the progressive phase of the disease. As noted by Sormani et al., albeit requiring further confirmation, AHSCT appears to have an overall higher disease activity- free survival rate when compared to all DMDs, regardless of the conditioning regimen employed. Moreover, transplant, due to the suppression of the inflammatory activity, require no further treatment to control the disease, and the condition of "remission" is prolonged. The sustained efficacy of the transplant reduces the patient discomfort, related to daily, weekly or monthly administration of drugs, and their collateral effects. New clinical trials will be briefly outlined at the end of the presentation.