Abstract
Rationale Phase I/Il studies of autologous hematopoietic stem cell transplantation (HSCT) for multiple sclerosis (MS) were initiated, based on results of experimental transplantation in animal models of multiple sclerosis and clinical observations in patients treated concomitantly for malignant disease. Patients Eighty-five patients with progressive MS were treated with autologous HSCT in 20 centers and reported to the autoimmune disease working party of the European Group for Blood and Marrow Transplantation (EBMT). 52 (61 %) were female, median age was 39 [20-58] years.
The median interval from diagnosis to transplant was 7 [1-26] years. Patients suffered from severe disease with a median EDSS score of 6.5 [4.5-8.5].
Active disease prior to transplant was documented in 79 of 82 evaluable cases. Results The stem cell source was bone marrow in 6 and peripheral blood in 79, and stem cells were mobilized into peripheral blood using either cyclophosphamide combined with growth factors or growth factors alone.
Three patients experienced transient neurological complications during the mobilization phase. The high dose regimen included combination chemotherapy, with or without anti-lymphocyte antibodies or, with or without, total body irradiation.
The stem cell transplants were purged of lymphocytes in 52 patients. Median follow-up was 16 [3-59] months.
There were 7 deaths, 5 due to toxicity and infectious complications, 2 with neurological deterioration. The risk of death of any cause at 3 years was 10 ( 7)% (95 % confidence interval).
Neurological deterioration during transplant was observed in 22 patients; this was transient in most but was associated with MS progression in 6 patients. Neurological improvement by ! I point in the EDSS score was seen in 18 (21 %) patients.
Confirmed progression-free survival was 74 ( 12)% at 3 years being 66 ( 23)% in patients with primary progressive MS but higher in patients with secondary progressive or relapsing-remitting MS, 78 ( 13) %; p = 0.59. The probability of confirmed disease progression was 20 (11)%.
MRI data were available in 78 patients before transplant showing disease activity (gadolinium enhancing, new or enlarging lesions) in 33 %. Posttransplant MRI showed activity at any time in 5/61 (8 %) evaluable cases.
Conclusion Autologous HSCT suggest positive early results in the management of progressive MS and is feasible. These multicentre data suggest an association with significant mortality risks especially in some patient groups and are being utilised in the planning of future trials to reduce transplant related mortality.