Reduced Intensity Conditioning Regimen of Autologous Hematopoietic Stem Cell Transplantation±Mitoxantrone Consolidation In Multiple Sclerosis
Authors: Novik Andrei A , Kuznetsov Aleksey N , Melnichenko Vladimir Y , Fedorenko Denis A , Kartashov Andrei V , Ionova Tatyana I , Kurbatova Kira A , Gorodokin Gary I 
Published: October 2019

Abstract
Abstract 372
High-dose immunosuppressive therapy (HDIT) with autologous hematopoietic stem cell transplantation (ASCT) offers promising results in the treatment of multiple sclerosis (MS) patients. Reduced intensity conditioning regimens (mini-ASCT) is a way to improve the balance between benefits and side effects of this treatment approach. The goal of our research was to study the safety and treatment outcomes of mini-ASCT±Mitoxantrone consolidation in patients with various types of MS. 177 patients with MS: secondary progressive (SP) – 64 patients, primary progressive (PP) – 27, progressive-relapsing (PR) – 4 and relapsing-remitting (RR) – 82 were included in this study (mean age - 33.0, range: 17–54; male/female – 73/104). BM (BCNU 300 mg/m2, melphalan 50 mg/m2) was used as conditioning regimen. There were two treatments arms, with (n=55) and without (n=122) Mitoxantrone consolidation after mini-ASCT. The patients with unfavorable risk factors were included in consolidation therapy arm. Median EDSS at base-line was 4.0 (range 1.5 – 8.5). The median follow-up duration was 24.4 months (range 6 – 48 months). Neurological evaluation was performed at baseline, at discharge, at 3, 6, 9, 12 months after ASCT, and every 6 months thereafter. MRI examination was performed at baseline, at 6, 12 months, and at the end of follow-up. No transplant-related deaths were observed. In addition, there were no deaths in the study within all follow-up. The mobilization and transplantation procedures were well tolerated with no unpredictable severe adverse events. All 90 patients included in the analysis in the first arm, namely, those patients who did not receive consolidation therapy after mini-ASCT, responded to treatment. In 12 months post-transplant 43% patients improved, 50% – stabilized, and 7% – progressed. At long-term follow-up (mean 36 months), the clinical response in 48% patients was classified as an improvement; 43% patients remained stable. Two patients deteriorated to a worse score after 18 months of stabilization (SP MS and RR MS), and 2 others progressed after 24 months of improvement (PP MS and SP MS). Overall clinical response in this group was 82%. The vast majority of patients (96%) with RR MS were relapse-free. No active, new or enlarging MRI lesions were registered in patients without disease progression. Remarkably, all patients in this group who did not have disease progression were off therapy throughout the post-transplant period. The analysis of clinical outcomes in the second treatment arm with consolidation after mini-ASCT was performed in 41 patients. Notably, there was no disease progression registered in this group. In addition, there were no relapses in the patients with RR MS. At long-term follow-up (24 months) the majority of patients achieved clinical improvement (62.5%); others had disease stabilization (37.5%). In conclusion, this study provides ample evidence in support of safety and efficacy of reduced intensity conditioning regimen of ASCT in patients with various types of MS. Mini-ASCT without consolidation leads to overall clinical response in 82% of MS patients. Preliminary data on consolidation with Mitoxantrone after mini-ASCT show a real possibility to achieve a relapse- and progression - free period with the mean of 24 months (range 7–45 months) in 100% patients. Further studies should be done to validate conditioning regimens in MS patients undergoing mini-ASCT and to define a role of consolidation after transplantation.

Disclosures:
No relevant conflicts of interest to declare.