Multicenter Experience of High Dose Chemotherapy (HDCT)+Autologous Stem Cell Transplantation (ASCT) in Multiple Sclerosis (MS) Patients.
Authors: Shevchenko Yury L. , Novik Andrei A. , Kuznetcov Alexey N. , Afanasiev Boris V. , Lisukov Igor A. , Rykavicin Oleg A. , Myasnikov Alexandr A. , Ionova Tatiana I. , Shamanski Sergey V. , Kulagin Andrey D. , Malysheva Olga A. , Baziy Nikolay I. , Melnichenko Vladimir Y. , Fedorenko Denis A. , Vereschagina Inna V. , Zdorov Andrey E. , Kishtovich Anton V. , Ivanov Roman A. , Fedotov Yury N. , Gorodokin Gary I. 
Published: October 2019

Abstract
During the last decade HDCT+ASCT is more often used as a therapeutic option for MS patients. The major treatment outcomes for MS patients are disease-progressive free period and improvement of patient’s quality of life (QoL). We aimed to study treatment outcomes in MS patients after early, conventional and salvage HDCT+ASCT.
Thirty two patients with MS (secondary progressive - 16 patients, primary progressive - 8, progressive-relapsing - 1, relapsing-remitting - 7) from 6 medical centers were included in this study (mean age - 32.0, range: 19–49; male/female - 12/20). Two patients underwent early HDCT +ASCT, 27 patients - conventional HDCT+ASCT and 3 patients - salvage HDCT+ASCT. Median EDSS at base-line was 6.0 (range 2.0 – 8.0). The median follow-up duration was 18 months (range 6 – 78 months). All of the patients had previously undergone conventional treatment. Neurological and QoL evaluation was provided at baseline, at discharge, 3, 6, 9, 12 months, and then every 6 months after HDCT+ASCT. MRI was conducted at baseline, at 6, 12 months, and at the end of follow-up. FACT-BMT and FAMS were used for QoL evaluation. QoL response was evaluated using Integral QoL index.
All 27 patients with the follow-up longer than 1 year, included in the analysis, experienced a clinical stabilization or improvement. More than half of them improved: 6 patients showed significant improvement in EDSS (by more than 1.0 point), 4 patients improved by 1.0 point, and 5 patients - by 0.5 points on EDSS. Twelve patients achieved stabilization. Two patients deteriorated to a worse score after 18 months of stabilization; 2 other patients progressed after 12 and 30 months of improvement, respectively. All the patients with clinical stabilization and improvement exhibited negative MRI scans.
Out of 21 patients included in the analysis of QoL response 19 exhibited improved QoL 6 months post-transplantation. At one year after HDCT+ASCT 1 patient exhibited excellent QoL response; 3 patients - good QoL response; 7 patients - moderate QoL response and 8 patients - minimal QoL response. At 2.5 years post-transplantation 3 more patients had excellent QoL response. Further QoL improvement was observed at longer follow-up. One of the patients who experienced progression after stabilization had no QoL response; another patient who progressed after stabilization had stable QoL during 6 months post-transplant and significantly worsened at 9 months.
In conclusion, clinical response was observed in 100% of MS patients after early, conventional and salvages HDCT+ASCT. The majority of patients with clinical response had a good or moderate QoL response. Further studies should be done to investigate the clinical and patient-reported outcomes of HDCT+ASCT in MS patients to better define treatment success.