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More MS news articles for April 2003

AAN: Immunoablation May Aid Multiple Sclerosis Patients

http://www.docguide.com/news/content.nsf/News/8525697700573E1885256CFC005A40A9

April 2, 2003
By Charlene Laino
Honolulu, HI

Immunoablative treatment followed by autologous stem cell transplantation can be accomplished with minimal and predictive toxicity in patients with early aggressive multiple sclerosis, a preliminary study suggests.

There are hints that the strategy may also be more effective than conventional immunosuppression, reported Mark S. Freedman, a professor of medicine in the department of neurology at the University of Ottawa and Director of the Multiple Sclerosis Research Clinic at the Ottawa Hospital in Canada. One-year data on the first six patients to undergo complete immunoablation followed by autologous stem cell transplantation were presented here on April 1st at the 55th Annual Meeting of American Academy of Neurology.

While immunosuppression with chemotherapeutic agents has been shown to transiently reduce disease activity both clinically and by magnetic resonance imaging studies, the continued presence of potentially disease-causing immune cells would predictably lead to disease recurrence, Dr. Freedman said. By inducing complete immunoablation, patients would conceivably achieve a long-lasting remission of disease activity.

"The idea is to reboot the immune system," he said in an interview. "The only way to do this is to wipe out the diseased immune system. And, then we rebuild it using stem cells."

In the procedure, a back-up bone marrow harvest is followed by stem cell mobilization with a bolus of high-dose chemotherapy and 10 days of 10 micrograms/kg/day of granulyte stimulating colony factor (G-CSF) to stimulate the bone marrow to kill out precursor cells.

Leukophoresed stem cells are then depleted of T cells using Miltenyii immunomagnetic CD34 positive selection. "This depletes the T cells so there is no chance of putting back some of the damaged cells," Dr. Freedman said.

After the patients are allowed to recover for a few weeks, immunoablation is accomplished using a series of high dose cyclophosphamide infusions and oral busulfan. "Based on animal studies, the thought is that the two-drug combination will cross the blood brain barrier and take out any remaining T cells," Dr. Freedman said.

About 10 days later, stem cells are re-infused into the patients, aided by treatment with 5 micrograms/kg/day of G-CSF "to help the stem cells kick in," he said.

All six depletions were successful, and there were signs that the new cells are from the graft and not from the body, Dr. Freedman reported. More notably, all six patients have stabilized or are improving at 1 year. Additionally, there has been no increase in the burden of disease on imaging studies. Atrophy appears to have stabilised in all six patients. "In every other study, there has been a deterioration in both of these factors at 1 year," he said.

While almost all the patients developed infections as well as transient Grade I-II toxicities such as stomatitis, "all the toxicities were predictable and manageable," Dr. Freedman said.

The bottom line: "The results are encouraging but preliminary," he said. "We'll have to see what happens after 1 year."

[Study title: Treatment of Aggressive MS Using Immunoablative Treatment with Autologous Stem Cell Rescue: One Year Clinical and Laboratory Follow-Up of the First Six Treated Patients. Abstract: S11.006]
 

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