Autologous haematopoietic stem cell transplantation with an intermediate intensity conditioning regimen in multiple sclerosis: the Italian multi-centre experience

Author:

Mancardi GL12,Sormani MP3,Di Gioia M4,Vuolo L56,Gualandi F7,Amato MP5,Capello E1,Currò D1,Uccelli A12,Bertolotto A8,Gasperini C9,Lugaresi A10,Merelli E11,Meucci G12,Motti L13,Tola MR14,Scarpini E15,Repice AM56,Massacesi L56,Saccardi R4,Donnini I,Bosi A,Guidi S,Bagigalupo A,Bonzano L,Bruzzi P,Roccatagliata L,Antenucci R,Granella F,Martino G,Rottoli M,Solaro C,Salvi F,Barilaro A,Capobianco M,

Affiliation:

1. Department of Neuroscience, Ophthalmology and Genetics, University of Genoa, Genoa, Italy.

2. Centre of Excellence for Biomedical Research, University of Genoa, Genoa, Italy.

3. Biostatistic Unit, Department of Health Sciences, University of Genoa, Genoa, Italy.

4. Bone Marrow Transplantation Unit, Careggi Hospital, Florence, Italy.

5. Department of Neuroscience, Careggi University Hospital, University of Florence, Florence, Italy.

6. Tuscan Regional MS Reference Center, Careggi University Hospital, University of Florence, Florence, Italy.

7. Bone Marrow Transplantation Unit, S. Martino Hospital, Genoa, Italy.

8. Regional Center for Multiple Sclerosis and Clinical Neurobiology, San Luigi Gonzaga Hospital, Orbassano, Italy.

9. Department of Neurosciences, San Camillo Forlanini Hospital, Rome, Italy.

10. MS Center, Department of Oncology and Neuroscience, University Gabriele D’Annunzio, Chieti-Pescara, Italy.

11. Department of Neurosciences, University of Modena and Reggio Emilia, Modena, Italy.

12. Division of Neurology and Neurophysiopathology, Livorno Hospital, Livorno, Italy.

13. MS Center, Santa Maria Nuova Hospital, Reggio Emilia, Italy.

14. Department of Neurology, Ferrara Hospital, Ferrara, Italy.

15. Department of Neurological Sciences, Ospedale Maggiore Policlinico, University of Milan, Milan, Italy.

Abstract

Background: Over recent years numerous patients with severe forms of multiple sclerosis (MS) refractory to conventional therapies have been treated with intense immunosuppression followed by autologous haematopoietic stem cell transplantation (AHSCT). The clinical outcome and the toxicity of AHSCT can be diverse, depending on the various types of conditioning protocols and on the disease phase. Objectives: To report the Italian experience on all the consecutive patients with MS treated with AHSCT with an intermediate intensity conditioning regimen, named BEAM/ATG, in the period from 1996 to 2008. Methods: Clinical and magnetic resonance imaging outcomes of 74 patients were collected after a median follow-up period of 48.3 (range = 0.8–126) months. Results: Two patients (2.7%) died from transplant-related causes. After 5 years, 66% of patients remained stable or improved. Among patients with a follow-up longer than 1 year, eight out of 25 subjects with a relapsing–remitting course (31%) had a 6–12 months confirmed Expanded Disability Status Scale improvement > 1 point after AHSCT as compared with one out of 36 (3%) patients with a secondary progressive disease course ( p = 0.009). Among the 18 cases with a follow-up longer than 7 years, eight (44%) remained stable or had a sustained improvement while 10 (56%), after an initial period of stabilization or improvement with median duration of 3.5 years, showed a slow disability progression. Conclusions: This study shows that AHSCT with a BEAM/ATG conditioning regimen has a sustained effect in suppressing disease progression in aggressive MS cases unresponsive to conventional therapies. It can also cause a sustained clinical improvement, especially if treated subjects are still in the relapsing–remitting phase of the disease.

Publisher

SAGE Publications

Subject

Neurology (clinical),Neurology

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