Long-term Clinical Outcomes of Hematopoietic Stem Cell Transplantation in Multiple Sclerosis
Giacomo Boffa, Luca Massacesi, Matilde Inglese, Alice Mariottini, Marco Capobianco, Lucia Moiola, Maria Pia Amato, Salvatore Cottone, Francesca Gualandi, Marco De Gobbi, Raffaella Greco, Rosanna Scimè, Jessica Frau, Giovanni Bosco Zimatore, Antonio Bertolotto, Giancarlo Comi, Antonio Uccelli, Alessio Signori, Emanuele Angelucci, Chiara Innocenti, Fabio Ciceri, Anna Maria Repice, Maria Pia Sormani, Riccardo Saccardi, Gianluigi Mancardi, Marta Radaelli, Vincenzo Pavone, Claudio Gasperini, Valerio Zoli, Luisa Caniatti, Francesco Lanza, Stefano Meletti, Marco Onofrj, G. Meucci, Elio Scarpini, Sara Montepietra, Umberto Aguglia, Franco Granella, Donata Guidetti, Luigi Ruiz, Anna Maria Raiola, Riccardo Varaldo, Elisabetta Capello, Elvira Sbragia, D. Curr`o, Alessandro Barilaro
Abstract
<h3>Objective</h3> To determine whether autologous hematopoietic stem cell transplantation (aHSCT) is able to induce durable disease remission in people with multiple sclerosis (MS), we analyzed the long-term outcomes after transplantation in a large cohort of patients with MS. <h3>Methods</h3> To be included, a minimum dataset (consisting of age, MS phenotype, Expanded Disability Status Scale [EDSS] score at baseline, information on transplantation technology, and at least 1 follow-up visit after transplantation) was required. <h3>Results</h3> Two hundred ten patients were included (relapsing-remitting [RR] MS 122 [58%]). Median baseline EDSS score was 6 (1–9); mean follow-up was 6.2 (±5.0) years. Among patients with RRMS, disability worsening–free survival (95% confidence interval [CI]) was 85.5% (76.9%–94.1%) at 5 years and 71.3% (57.8%–84.8%) at 10 years. In patients with progressive MS, disability worsening–free survival was 71.0% (59.4%–82.6%) and 57.2% (41.8%–72.7%) at 5 and 10 years, respectively. In patients with RRMS, EDSS significantly reduced after aHSCT (<i>p</i> = 0.001; mean EDSS change per year −0.09 [95% CI −0.15% to −0.04%]). In patients with RRMS, the use of the BCNU+Etoposide+Ara-C+Melphalan (BEAM) + anti-thymocyte globulin (ATG) conditioning protocol was independently associated with a reduced risk of no evidence of disease activity 3 failure (hazard ratio 0.27 [95% CI 0.14–0.50], <i>p</i> < 0.001). Three patients died within 100 days from aHSCT (1.4%); no deaths occurred in patients transplanted after 2007. <h3>Conclusions</h3> aHSCT prevents disability worsening in the majority of patients and induces durable improvement in disability in patients with RRMS. The BEAM + ATG conditioning protocol is associated with a more pronounced suppression of clinical relapses and MRI inflammatory activity. <h3>Classification of Evidence</h3> This study provides Class IV evidence that for people with MS, aHSCT induces durable disease remission in most patients.