Autologous hematopoietic stem cell transplantation in relapsing-remitting multiple sclerosis: comparison with secondary progressive multiple sclerosis

María Carcelén-Gadea,Isidro Jarque,Francisco Pérez-Miralles,Arantxa Navarré,Francisco Coret,Javier Mallada,Francisco Gascón,Carmen Alcalá,Miguel Angel Sanz,Sara Gil-Perotin,Jaime Sanz,Isabel Boscá,Carlos Solano,Bonaventura Casanova,Javier De La Rubia,Angeles Cervelló,Juan Carlos Hernández-Boluda

doi:10.1007/s10072-017-2933-6

Abstract

The main objective of our work is to describe the long-term results of myeloablative autologous hematopoietic stem cell transplant (AHSCT) in multiple sclerosis patients. Patients that failed to conventional therapies for multiple sclerosis (MS) underwent an approved protocol for AHSCT, which consisted of peripheral blood stem cell mobilization with cyclophosphamide and granulocyte colony-stimulating factor (G-CSF), followed by a conditioning regimen of BCNU, Etoposide, Ara-C, Melphalan IV, plus Rabbit Thymoglobulin. Thirty-eight MS patients have been transplanted since 1999. Thirty-one patients have been followed for more than 2 years (mean 8.4 years). There were 22 relapsing-remitting multiple sclerosis (RRMS) patients and 9 secondary progressive multiple sclerosis (SPMS) patients. No death related to AHSCT. A total of 10 patients (32.3%) had at least one relapse during post-AHSCT evolution, 6 patients in the RRMS group (27.2%) and 4 in the SPMS group (44.4%). After AHSCT, 7 patients (22.6%) experienced progression of disability, all within SP form. By contrast, no patients with RRMS experienced worsening of disability after a median follow-up of 5.4 years, 60% of them showed a sustained reduction in disability (SRD), defined as the improvement of 1.0 point in the expanded disability status scale (EDSS) sustains for 6 months (0.5 in cases of EDSS ≥ 5.5). The only clinical variable that predicted a poor response to AHSCT was a high EDSS in the year before transplant. AHSCT using the BEAM-ATG scheme is safe and efficacious to control the aggressive forms of RRMS.

Highlights

Multiple sclerosis (MS) is a heterogeneous inflammatory disease affecting the central nervous system (CNS), in which a deep immunological alteration is in the origin of the pathologic phenomena that occurs in MS patients and lead to the progressive and irreversible degeneration of the CNS [1].Despite advances in the treatment of MS, many patients do not respond to available drugs and require other therapeutic strategies to control disease activity and to prevent the progression of disability [2, 3].Neurol Sci (2017) 38:1213–1221Autologous hematopoietic stem cell transplantation (AHSCT) has been recognized since the final of the last century as a therapeutic option for very aggressive MS patients [4]
According to recent data published in the largest observational study, the results of autologous hematopoietic stem cell transplant (AHSCT) in relapsingremitting multiple sclerosis (RRMS) (16% of the series) progression-free patients ranged from 90% [10] to 100% [11]
There were no demographic differences between groups, but the expanded disability status scale (EDSS) in the previous 2 years, the year before, and baseline was high in the secondary progressive multiple sclerosis (SPMS), and the number of relapses was significant higher in RRMS

Summary

Introduction

Multiple sclerosis (MS) is a heterogeneous inflammatory disease affecting the central nervous system (CNS), in which a deep immunological alteration is in the origin of the pathologic phenomena that occurs in MS patients and lead to the progressive and irreversible degeneration of the CNS [1].Despite advances in the treatment of MS, many patients do not respond to available drugs and require other therapeutic strategies to control disease activity and to prevent the progression of disability [2, 3].Neurol Sci (2017) 38:1213–1221Autologous hematopoietic stem cell transplantation (AHSCT) has been recognized since the final of the last century as a therapeutic option for very aggressive MS patients [4]. Despite advances in the treatment of MS, many patients do not respond to available drugs and require other therapeutic strategies to control disease activity and to prevent the progression of disability [2, 3]. MS patients with high inflammatory activity in the earliest stages of the disease, who show refractoriness to standard therapies, may respond well to AHSCT, with a transplant-related mortality that has decreased from 5.3% [7] to 1.3% [8]. According to recent data published in the largest observational study, the results of AHSCT in relapsingremitting multiple sclerosis (RRMS) (16% of the series) progression-free patients ranged from 90% [10] to 100% [11]

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Conclusion