Friday June 06, 2003
Boston Cure Project for Multiple Sclerosis
As previously reported in MSNews, a multi-center stem cell transplantation trial coordinated by the Fred Hutchinson Cancer Research Center in Seattle has recently concluded. The formal results will soon be available in an issue of the journal "Blood".
This was a pilot study designed to study safety more than efficacy, but naturally some efficacy results were obtained as well. Participants all had an EDSS from 5 to 8 with a worsening of 1 or more points in the year preceding the trial. The treatment regimen consisted of (1) mobilization and collection of stem cells, (2) administration of prednisone (after one early subject suffered an MS flare during mobilization), (3) immunosuppressive doses of irradiation and chemotherapy, (4) reinfusion of the subjects' own stem cells, and (5) in the last eight patients, an additional short course of prednisone to prevent an engraftment syndrome (fever plus rash) from developing. Subjects were kept in the hospital until their immune systems were sufficiently restored and any complications were resolved.
Clinical outcomes were variable, the worst outcome being the death of one subject after a few weeks due to viral infection as a result of the treatment. This person was given the immunosuppressant rabbit ATG instead of horse ATG because of a negative reaction to horse ATG; however, because rabbit ATG is a stronger immunosuppressant, this regimen resulted in a longer lasting depletion of T cells which presumably allowed the infection to develop. (Other subjects experienced various types of infections during the trial, but in general these resolved easily.) Another subject experienced continuing neurological losses and died at month 23 after treatment (this subject had developed a persistent engraftment syndrome). No long-term toxicities were reported except for one case of hypothyroidism at one year after treatment.
As for efficacy measures, of the remaining 24 subjects, five had an increase in EDSS of more than one point; three had unconfirmed increases of 0.5 point; two had decreases of 0.5 point; and 14 remained stable as of their last follow-up at 3 to 36 months after treatment. Four subjects showed new or enhancing lesions on MRI post-treatment, but only one had an increase in T2 burden. A subset of subjects were evaluated with serial MRI over the year following treatment. Overall, in these subjects lesion volume decreased by 6.6% and total brain volume decreased by only 1.8%.
While this type of treatment is definitely more risky than conventional
treatments, the data presented here indicate that it may be able to stabilize,
at least for up to a few years, some particularly debilitated people. Certain
modifications to the regimen were made during the study to improve safety,
and more will likely follow after further analysis. The authors recommend
further trials of this therapy, with more attention to efficacy measures
to better assess its advantages over existing therapies.
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