Self-reported changes in the expanded disability status scale score in patients with multiple sclerosis after autologous stem cell transplants: real-world data from a single center

Abstract

In order to reset the immune system to baseline function, autologous hematopoietic stem cell transplantation (HSCT) has been performed in patients with multiple sclerosis (MS). After June 2015, 617 new consecutive patients with MS were autografted in our center with non-frozen peripheral blood stem cells. The autografts were performed on an outpatient basis, after conditioning with cyclophosphamide and rituximab. The aim of the study was the assessment of both safety and efficacy of the method. The study's primary co-end-points were recovery of granulocyte and platelet counts and transplant-related mortality. Secondary endpoints were overall survival and clinical response (improvement or stabilization of the self-reported expanded disability status scale score). The protocol was registered in ClinicalTrials.gov identifier NCT02674217.0. We included 401 females and 216 males, with a median age of 46 years. A total of 259 patients had relapsing-remitting MS (RRMS), 228 had secondary progressive (SPMS) and 130 had primary progressive (PPMS) multiple sclerosis. All procedures were initially performed on an out-patient basis and only 32 individuals (5%) required hospitalization. One to three aphereses (median 1) were required to harvest at least 1 × 10 6 /kg viable CD34 + cells. The total number of viable CD34 + infused cells ranged between 1 and 37·83 × 10 6 /kg (median 5·68). Patients recovered more than 0·5 × 10 9 /l absolute granulocytes by day 8 (median, range = 2-14), and platelet values were above 20 × 10 9 /l by day 4 (median, range = 0-11). Eleven individuals required red blood cells and six needed platelet transfusions. To date, there have been no deaths attributable to the transplant, yielding a 30-month overall survival of 100%. Patients have been followed for 3-42 months (median = 12). The overall response rate (decrease or stabilization of the self-reported EDSS score) at 12 months was 78% for all patients (83% in RRMS, 78% in PPMS and 73% in SPMS), while the disability progression-free survival was 82% for all patients (86% in RRMS, 78·5% in SPMS and 78% in SPMS). Changes in the self-reported EDSS score in parallel with neurological improvement were observed in people with all types of MS after HSCT, employing the 'Mexican method' .

The 1,000th Transplant for Multiple Sclerosis and Other Autoimmune Disorders at the HSCT-México Program: A Myriad of Experiences and Knowledge

“…Although this study was limited due to the lack of a comprehensive follow-up assessment, i.e., the EDSS score evaluation at the given time points was achieved in 72% of all patients (240 patients at 1 year, 136 at 2 years, and 19 at 3 years). These results could demonstrate a consistent effect across all groups and period of study ( 8 ).…”

“…Having proved that the Mexican HSCT method was both feasible ( 10 ) and safe ( 11 ), we have recently analyzed data of its efficacy in a group of 617 MS patients ( 8 ), this being the largest published single-center experience of HSCT in persons with MS. In this communication, a significant reduction in the EDSS score was achieved in all the three phenotypes of MS (from a median of 5.1 to 4.5 points) 12 months after the transplant, whereas the response rate (defined as a decrease of at least 0.5 of EDSS score regardless of baseline EDSS, or unchanged EDSS) was 83, 78, and 73% after 12 months in the relapsing-remitting, primary-progressive and secondary-progressive forms of MS, respectively.…”

“…Several international academic societies have recognized its important role in the treatment of people with MS ( 2 , 3 ), mainly in the more inflammatory variants of the disease (relapsing-remitting MS). We and others have been researching this area in recent years ( 4 – 8 ). After gaining experience conducting both auto and allografts in persons with hematological diseases in the HSCT programs in Puebla and Monterrey ( 9 ), we engaged in autografting patients with autoimmune conditions.…”

Post Transplantation Cyclophosphamide Improves Outcome of Autologous Hematopoietic Stem Cell Transplantation in Animal Model of Multiple Sclerosis

“…This study provides the experimental background that could be used for establishing a similar procedure in patients—moving a part of the Cy from conditioning into post HSCT treatment. The study of the splitting of the Cy dose into premobilization and conditioning shows very promising results (Ruiz-Argüelles et al 2019 , 2017 ). The approach presented in our study might help to maintain the dose density of chemotherapy and possibly improve the clinical outcome.…”

Stem Cell Therapy in Neuroimmunological Diseases and Its Potential Neuroimmunological Complications

“…A total of 44 phase I, I/II, and II studies, as well as registered clinical trials and post hoc analyses on cell therapy for MS, were found, and a summary of the results is shown in Table 1 (for further details, see Supplementary Table S1 ) [ 9 , 17 , 24 , 25 , 26 , 27 , 28 , 29 , 30 , 31 , 32 , 33 , 34 , 35 , 36 , 37 , 38 , 39 , 40 , 41 , 42 , 43 , 44 , 45 , 46 , 47 , 48 , 49 , 50 , 51 , 52 , 53 , 54 , 55 , 56 , 57 , 58 , 59 , 60 , 61 , 62 , 63 , 64 , 65 , 66 , 67 , 68 ]. The number of included patients in these studies varied between five and 617, with most investigating chronic–progressive forms of MS (five trials included relapsing–remitting MS patients only).…”