Clinical and MRI outcome after autologous hematopoietic stem cell transplantation in MS
Saiz A, Blanco Y, Carreras E, Berenguer J, Rovira M, et al.;
Commented by , 23 Mar 2004
Background
Multiple sclerosis (MS) is considered to be a T-cell mediated autoimmune disease, and immunosupressive/modulating treatment has proved to reduce disease progression. Disease modifying treatment with b-interferon and glatiramer acetete is standard, although often insufficient in patients with severe disease course.
A more aggressive treatment approach, using high dose chemotherapy with mitoxantrone, has been successful in these cases. During the last decade, trials of autologous stem cell transplantation (ASCT) has been conducted and recently a multicentre retrospective analysis has shown promising results (ref. 1).
Aim
To describe the 3 year clinical outcome and MRI evolution after AHSCT.
Methods
15 patients were included in the prospective protocol after T-cell depleated AHSCT. 14 patients completed the study. Disease course was secondary progressive (SP; n=6) or relapsing remitting (RR; n=9) MS, median Kurtzke’s Expanded Disability Status Scale (EDSS) score was 6.0, median number of relapses in the year prior to AHSCT was 3 in the entire group and 6 in the RR group.
Median EDSS increase in the year prior to AHSCT was 1.0 in the SP group and 1.5 in the RR group. Grafts were depleated of T cells by CD 34+ immunomagnetic selection, conditioning included carmustine, cyclophosphamide and antithymocyte globulin treatment.
The 3-year progression free survival was defined as the probability to be alive without increase in EDSS after AHSCT. The 3-year disease activity-free survival was defined as the probability to be alive without progression of any type.
Results
Neurologic deterioration was seen in 3 patients after AHSCT. After 36 months, EDSS remained stable in eight patients, improved in four (median 1.0; range 0.5-1.5), and worsened in two (1.0 and 1.5). The 3-year actuarial probability of progression-free survival was 85.7%, and disease activity-free survival was 46.4%.
MRI showed no T1-enhancing lesions after AHSCT. Mean percentage reduction in T2 lesion volume at 3 years was 20.2% compared with baseline and corpus callosum area was reduced 12.7%. The main reduction in these measurements was seen during the first year.
Discussion
The paper presents the first long term prospective AHSCT data, which show a sustained progression-free course 3 years after treatment in most patients. MRI data showed no active lesions and a moderate reduction in T2 lesion volume.
The corpus callosum area was also reduced, and the authors speculate that this might be caused by resolution of edema and inflammation after treatment.
The pilot study shows promising results, although it is evident that AHSCT does not cure MS. The morbidity of the treatment is high (app. 5-8% in high risk cases) and therefore it still remains an experimental option, for severe and medically refractory cases, in the setting of an approved protocol.
An important consideration is to what extent intensive immuno-suppression alone account for the observed effects. A randomized trial is currently planned comparing AHSCT to mitoxantrone (Autologous Stem Cell Transplantation International Multiple Sclerosis Trial), which might provide answers in this regard
References
1. Fassas et al., J Neurol 2002;249:1088-97
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