Which Strategy of Immunoablative Therapy with Autologous Stem Cell Transplantation (ASCT) Is Preferable in Multiple Sclerosis (MS) Patients?.

Abstract

During the last decade immunoablative therapy with ASCT (IT+ASCT) has been used with increasing frequency as a therapeutic option for MS patients. Among a number of unanswered questions is the timing of IT+ASCT. We have identified 3 strategies of IT+ASCT depending on the stage in disease process: early, conventional and salvage/late. The goal of our research was to study clinical and patient-reported outcomes in MS patients after early, conventional and salvage/late transplantation. 54 patients with MS (secondary progressive - 26 patients, primary progressive -10, progressive-relapsing - 1, and relapsing-remitting - 17) from 6 medical centers were included in this study (mean age - 32.0, range: 17–51; male/female - 21/33). 13 patients underwent early, 37 patients - conventional, and 4 patients - salvage/late transplantation. Median EDSS at base-line was 6.0 (range 1.5 – 8.0). The median follow-up duration was 18 months (range 6 – 84 months). Neurological and quality of life (QoL) evaluation was performed at baseline, at discharge, at 3, 6, 9, 12 months, and every 6 months thereafter following IT+ASCT. MRI examinations were conducted at baseline, at 6, 12 months, and at the end of follow-up. FACT-BMT and FAMS were used for QoL evaluation. Notably, no transplant-related deaths or unpredictable severe adverse events were observed. All 42 patients (6 - early transplantation; 32 - conventional transplantation; 4 - salvage/late transplantation) with the follow-up of longer than 9 months experienced clinical stabilization or improvement. More than half of them (27 patients) improved: 8 patients showed significant improvement in EDSS, 9 patients improved by 1.0 point, and 10 - by 0.5 points on EDSS. Notably, all of the patients after early transplantation (mean age - 28.0) improved at least by 0.5 points on EDSS. 15 patients achieved stabilization. 2 patients deteriorated to a worse score after 18 months of stabilization; 2 others progressed after 12 and 30 months of improvement, respectively. All of the patients with clinical stabilization and improvement had negative MRI scans. Out of 24 patients included in QoL analysis 22 exhibited improved QoL 6 months post-transplantation. In conclusion, IT+ASCT appears to be an effective treatment for MS both in terms of clinical and patient-reported outcomes. The data obtained point to feasibility of early, conventional and salvage/late transplantation in MS patients. Our data support the hypothesis that transplantation is more effective in young patients at early stages of rapidly progressing disease. Further studies should be done to establish the best timing for transplantation and to validate IT+ASCT regimens in patients receiving early, conventional and salvage transplantation.