Haematopoietic Stem Cell Transplantation for Multiple Sclerosis: Current Status.

Autologous haematopoietic stem cell transplantation (AHSCT) is a treatment option for aggressive forms of multiple sclerosis (MS) that has been derived from haematological indications and repurposed for treatment of refractory autoimmune diseases. In the present review, a search for clinical studies on AHSCT was performed on the PubMed website and ClinicalTrials.gov databases. Papers were selected according to the following criteria: text written in English language, publication date between 2014 and August 2019, and reports including more than five patients. Prospective randomised and uncontrolled trials and retrospective case series were reviewed to examine the safety and efficacy of the procedure. Treatment protocols, pathological data and economic aspects of AHSCT were also succinctly covered. Growing evidence suggests that long-term suppression of inflammatory activity with stabilization or improvement of disability can be achieved in a high proportion of properly selected patients. More sophisticated outcome measures recently adopted, including effect on brain atrophy and disease biomarkers, are giving further insight into the effectiveness of transplant. The risks of the procedure have decreased to levels that can be considered acceptable for treatment of individuals with aggressive forms of MS. Careful selection of patients with an expected good benefit/risk profile, which is maximal when AHSCT is performed in early phases of the disease, and the expertise of transplant centres are critical to the success of treatment. Higher efficacy of AHSCT than with conventional treatments has recently been demonstrated by one randomised trial and further evidence is awaited from ongoing and planned trials comparing AHSCT with the most effective disease-modifying therapeutic agents.

In Vivo Assessment of Brain White Matter Inflammation in Multiple Sclerosis with (18)F-PBR111 PET.

UNLABELLED: PET radioligand binding to the 18-kD translocator protein (TSPO) in the brains of patients with multiple sclerosis (MS) primarily reflects activated microglia and macrophages. We previously developed genetic stratification for accurate quantitative estimation of TSPO using second-generation PET radioligands. In this study, we used (18)F-PBR111 PET and MR imaging to measure relative binding in the lesional, perilesional, and surrounding normal-appearing white matter of MS patients, as an index of the innate immune response. METHODS: (18)F-PBR111 binding was quantified in 11 MS patients and 11 age-matched healthy volunteers, stratified according to the rs6971 TSPO gene polymorphism. Fluid-attenuated inversion recovery and magnetization transfer ratio (MTR) MR imaging were used to segment the white matter in MS patients as lesions, perilesional volumes, nonlesional white matter with reduced MTR, and nonlesional white matter with normal MTR. RESULTS: (18)F-PBR111 binding was higher in the white matter lesions and perilesional volumes of MS patients than in white matter of healthy controls (P < 0.05). Although there was substantial heterogeneity in binding between different lesions, a within-subject analysis showed higher (18)F-PBR111 binding in MS lesions (P < 0.05) and in perilesional (P < 0.05) and nonlesional white matter with reduced MTR (P < 0.005) than in nonlesional white matter with a normal MTR. A positive correlation was observed between the mean (18)F-PBR111 volume of distribution increase in lesions relative to nonlesional white matter with a normal MTR and the MS severity score (Spearman ρ = 0.62, P < 0.05). CONCLUSION: This study demonstrates that quantitative TSPO PET with a second-generation radioligand can be used to characterize innate immune responses in MS in vivo and provides further evidence supporting an association between the white matter TSPO PET signal in lesions and disease severity. Our approach is practical for extension to studies of the role of the innate immune response in MS for differentiation of antiinflammatory effects of new medicines and their longer term impact on clinical outcome.