Autologous Hemopoietic Stem Cell Transplantation for Aggressive Multiple Sclerosis: A 17-Year Follow-Up Study in China

Abstract

Background: Autologous hematopoietic stem cell transplantation (AHSCT) may be a promising therapy for patients with aggressive multiple sclerosis (MS) unresponsive to standard treatments, but similar evidence is still limited. To assess the long-term outcomes in patients with aggressive MS receiving AHSCT with an intermediate intensity conditioning. Methods: This prospective single-center cohort study was conducted in consecutive patients with aggressive MS in the wards of Departments of Neurology and Hematology by a multidisciplinary team on aggressive MS in Xuanwu Hospital of Capital Medical University (Beijing, China) from February 1, 2001 to December 30, 2010. 47 consecutive patients were screened, 9 did not meet inclusion criteria, 1 declined the treatment and 1 had disease activity during study pending, 36 volunteer patients enrolled in the study. The last patient visit was on September 26, 2018, and data analysis was performed between October 15, 2018 and March 18, 2019. All patients received AHSCT with the modified BEAM (carmustine, etoposide, cytarabine, and melphalan) with teniposide instead of etoposide, and regularly assessed by the Expanded Disability Status Scale (EDSS) score and annual relapse rate (ARR). Demographic, treatment-related, and disease-related exposures were collected as variables of interest, including gender, age of onset, disease subtype, duration from MS diagnosis to AHSCT, the baseline EDSS score, number of treatments before transplantation, the highest EDSS score before transplantation, and ARR before transplantation. Primary outcomes were long-term progression-free survival and overall survival, and secondary outcomes were any transplant-related morbidity and severe adverse events. Findings: The median follow-up was 12.5 years (range, 3-17 years). And the 3-, 5-, 10-, and 17-year probabilities of progression-free survival as assessed by EDSS score were 81%, 72%, 44%, and 17%, respectively, whereas overall survival rates were 97%, 92%, 78%, and 63%, respectively. Factor associated with neurological progression-free after the transplantation was age of 25-34 year at disease onset (25-34 vs. 1 vs. ≤1: HR, 12.20; 95% CI, 2.21-67.36) were associated with a longer survival time. No transplant-related morbidity or severe adverse events were reported after the transplantation. Interpretation: Our study with the most extended follow-up period supports the importance of treating aggressive MS by AHSCT and revealed that age at disease onset over 25 years and lower ARR were associated with better outcomes. The results suggest that the appropriate choice of MS patients for AHSCT is critical for winning a better outcome. Funding: This study was supported by research grants from the National Natural Science Foundation of China (81771862, 81571633), the Beijing Natural Science Foundation (KZ201710025017), the Beijing Municipal Hospital Research and Development Plan (PX2017069), the Beijing Hundred, Thousand, and Ten Thousand Talents Project (2017-CXYF-09), the National Key R&D Program of China (2017YFC1310001, 2017YFC0907700), and the Beijing Municipal Science and Technology Project (Z171100000117016). Declaration of Interest: Authors declare no conflict of interest. Ethical Approval: The Ethics Committees of Xuanwu Hospital approved this study.