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

Abstract

After gaining experience conducting both auto and allografts in persons with hematological diseases in the HSCT programs in Puebla and Monterrey, México, this study outlines subsequent program autografting patients with autoimmune conditions. The first transplant in multiple sclerosis was conducted in Puebla on July 5, 2006. From 2015 we increased activity autografting persons with autoimmune conditions in the two campuses of the HSCT-México program: Puebla and Monterrey. By December 6, 2020, patient number 1,000 in the program was autografted. In our experience, a significant reduction in the expanded disability status scale score was achieved in all of the three phenotypes of the disease (from a median of 5.1 to 4.5 points), 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 multiple sclerosis, respectively. In addition to analyzing the viability, safety, and efficacy of our method, this study contributes new knowledge to the field of both stem cell transplantation and multiple sclerosis.

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

“…Another important issue is the possible impact of post-transplantation Cy on complications of the AHSCT procedure. The reported rates of mortality and complications in AHSCT are low (Burt et al 2019 ; Mancardi et al 2015 ; Murrieta-Álvarez et al 2021 ; Nash et al 2015 )—increasing the toxicity by additional chemotherapy might negatively impact safety. Post Cy in MS prolongs engraftment time in haploidentical transplants so a similar effect can be expected in AHSCT (Bacigalupo and Giammarco 2019 ; Im et al 2013 ).…”

“…One approach to reduce the risk is to modify the protocol and split the doses of cyclophosphamide instead of increasing it. This approach has been tested in AHSCT in MS where the cyclophosphamide was split into a mobilization and a conditioning dose—reducing the toxicity of the approach while maintaining the effectiveness (Murrieta-Álvarez et al 2021 ).…”

“…The CD34+ selection of grafts has not been tested in a randomized study in AHSCT in MS but the available data do not show an improvement of results by this graft modification (Nash et al 2015 ). The rate of serious complications connected with AHSCT in autoimmune diseases is relatively low compared with other diseases—in a recent series of 1000 patients, the mortality rate was 0.2% and serious adverse events were observed in a few percent of cases (Murrieta-Álvarez et al 2021 ).…”

Splitting the Total Dose of Cyclophosphamide in Two Blocks Apart during the Conditioning of Autologous Hematopoietic Stem Cell Transplantation in Multiple Sclerosis Results in Diminished Cardiotoxicity: Experience in 1,000 Patients

“…Autologous hematopoietic stem cell transplantation (HSCT) has been given to persons with multiple sclerosis (MS) for over 20 years, and more than 3000 HSCTs have been done worldwide 1,2 . Transplant-related mortality in MS managed with HSCT, was considered a limiting factor but has decreased to <2% 2 .…”

“…Autologous hematopoietic stem cell transplantation (HSCT) has been given to persons with multiple sclerosis (MS) for over 20 years, and more than 3000 HSCTs have been done worldwide 1,2 . Transplant-related mortality in MS managed with HSCT, was considered a limiting factor but has decreased to <2% 2 . We have conducted autotransplants in patients with all phenotypes of MS since 2006 and found an overall response rate of around 80% after grafting 1000 patients 2 .…”