Riccardo Saccardi

MD, Hematologist, Director, SODc Cellular Therapies and Transfusion Medicine
Careggi University Hospital, Florence, Italy
Riccardo Saccardi
Ricccardo Saccardi is a hematologist, involved over the last 20 years in the field of HSCT. He served as Chairman of the Autoimmune Diseases Working Party of the EBMT for two mandates, with a special focus on multiple sclerosis. His scientific activity is aimed at developing clinical research in the field of HSCT for severe Multiple Sclerosis and his laboratory activities have been predominantly dedicated to cell manipulation for transplantation, with a particular emphasis on the banking of umbilical cord blood stem cells. R. Saccardi is currently Director of the Cellular Therapies and Transfusion Medicine Department at Careggi University Hospital, Florence, which also includes management of the Cord Blood Bank and clinical units of the bone marrow transplant lab and processing lab for the transplant program, the Tissue-Muscle Bank and Transfusion Medicine. In 2011, he was Scientific Director of an international research project on the impact of storing methods in umbilical cord blood cell transplantation, overseen by Eurocord, со-funded by the Italian National Transplant Centre and National Blood Centre. He is also a board member of GITMO and co-author of over 120 publications in indexed journals (h Index 25), mostly in the field of HSCT and cellular therapy.
Autologous Stem Cell Transplantation in MS
EBMT Experience

Sharing the Experience at International Conference in Moscow, Russia, November 2019
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.

Alexander Lila, Lidiya Ananieva, Evgeniy Nasonov
Scientific Research Institute of Rheumatology named after V.A. Nasonova of the Ministry of Healthcare of Russian Federation, Moscow, Russian Federation