Haematopoetic stem cells in MSSaturday, October 13, 2007, 11:10 - 11:22
Immune ablation and autologous stem cell transplantation for aggressive multiple sclerosis: interim 5-year reportM.S. Freedman, H.L. Atkins, D.L. Arnold, A. Bar-Or on behalf of the Canadian BMT Study Group
Background: Complete immune ablation and reconstitution de novo with autologous bone-marrow derived stem cells halting all ongoing multiple sclerosis (MS) immune-mediated activity substantiates that MS arises from an acquired immune defect.
Methodology: A non-randomized phase II trial of immunoablation and autologous hematopoietic T cell-depleted stem cell transplantation (ASCT) for aggressive MS failing contemporary treatment. Inclusion criteria were: Age 18-50; active MS with relapses and expanded disability status scale (EDSS) progression. Patients had to be at high risk of progression determined by any of the following: multiple relapses (>5 in 1st 2-3 years); EDSS functional system scores (FSS) >=3 in pyramidal/cerebellar within first 5 years; EDSS >=3 and <=6; Evidence of current disease activity: >=1 point EDSS deterioration in past 18 months (EDSS <=5.0) or >=0.5 point EDSS deterioration (EDSS >=5.5) >=2 significant relapses in last year or 3 significant relapses in past 2 years. Immunoablation regimen: busulphan (9.6-16 mg/kg); cyclophosphamide (200 mg/kg); rabbit ATG (5mg/kg). Prospective follow-up included clinical, advanced MR imaging and immune studies.
Results: 25 patients were screened; 15 received full treatment; 2 patients elected to be “controls” (no ablative/ASCT treatment). The current interim report follows the patient progress after 5.5 years or 552 patient-months (range 3-69; median 35 months). Not a single patient experienced any further attacks or developed any new MRI lesions. Progression has been mild and noted only in those patients with high EDSS >=6.0 (n=4), whereas some patients with lower EDSS at baseline showed improvement (n=3). Overall, stability or improvement was seen in 9 patients. There were signs of specific recovery in certain FSS. A single death early on was due to busulfan-induced complications, but protocol changes resulted in a more tolerable regimen.
Conclusions: Immunoablation and ASCT results in clinical stabilization or improvement in aggressive forms of MS. Some patients have actually seen some improvement in terms of their motor capabilities, raising the possibility that the treatment does more than simply stop ongoing disease activity.