Treatment Outcomes in Multiple Sclerosis (MS) Patients after Early, Conventional and Salvage High Dose Chemotherapy (HDCT)+Autologous Stem Cell Transplantation (ASCT).
Authors: Shevchenko Yury L. , Novik Andrei A. , Afanasiev Boris V. , Lisukov Igor A. , Ionova Tatiana I. , Kulagin Andrei D. , Malysheva Olga A. , Bisaga Gennady N. , Melnichenko Vladimir J. , Voloshin Sergei V. , Fedorenko Denis A. , Vereschagina Inna V. , Kishtovich Anton V. , Fedotov Yury N. , Gorodokin Gary I. 
Published: April 2020

Abstract
HDCT+ASCT is a new and promising therapy for MS patients. Among a number of unclear questions is the terms of conducting HDCT+ASCT. According to our concept there are 3 strategies of HDCT+ASCT depending on the terms of disease process: early, conventional and salvage. Another important consideration is that the major treatment outcomes for MS patients are disease-progressive free period and improvement of patient’s quality of life (QoL). With this in mind, evaluation of both clinical and patient-reported outcomes in MS patients after HDCT+ASCT is worthwhile. We aimed to study the clinical and QoL response in MS patients after early, conventional and salvage HDCT +ASCT.
17 patients with MS (secondary progressive − 8 patients, primary progressive − 6, progressive relapsing − 2, relapsing remitting − 1) were included in the study (mean age − 32.3, SD − 6.6; male/female − 4/13). Fifteen patients underwent conventional HDCT +ASCT; one patient (relapsing-remitting MS) - early HDCT+ASCT and one patient (primary progressive MS) - salvage HDCT+ASCT. Median EDSS at base-line was 6.0 (range 2.0 – 7.5). The median follow-up duration was 12 months (range 6 – 72 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. 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, which was calculated by the method of integral profiles.
14 (82.4%) out of 17 patients including 12 patients with conventional HDCT+ ASCT, one patient with early HDCT+ ASCT and one patient with salvage HDCT+ ASCT experienced a clinical stabilization or improvement. Three patients showed significant improvement in EDSS (by more than 1.0 point), 2 patients improved by 1.0, and 3 patients - by 0.5. Six cases remained stable.
All of the patients with clinical stabilization and improvement exhibited negative MRI scans. One patient continuously worsened and died 3 years after the transplantation. Two other patients worsened by 0.5 points in their EDSS.
All patients with clinical response exhibited improved QoL at 6 months post-transplant and they preserved improved QoL at the end of follow-up. At one year after HDCT+ASCT the patients exhibited a good or excellent QoL response. These levels of QoL response were preserved throughout the follow-up period.
In conclusion, clinical response was observed in 82.4% MS patients after HDCT+ASCT. Notably, patients undergoing early, conventional and salvage HDCT+ASCT exhibited clinical response. All patients with clinical response had good or excellent QoL response. Thus, HDCT+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 HDCT+ASCT in MS patients. Further studies should be done to investigate clinical and QoL response in MS patients receiving early, conventional and salvage HDCT+ASCT to better define treatment success.