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More MS news articles for December 2002

ECFS: Immunoablation and Immunoreconstruction: First Promising Results in Rapidly Advancing MS Patients

November 29, 2002
By Adrian Burton
Special to DG News
Seville, Spain

Initial results suggest immunoablation followed by autologous stem cell transplantation to reconstruct the immune system is not only possible and tolerable but also clinically beneficial in rapidly progressing multiple sclerosis (MS).

The cause of MS is still unknown, although several theories about its origin exist

"We wanted to wipe out immunological memory," said Mark Freedman, MD, professor of neurology at University of Ottawa, in Ottawa, Canada, reporting results here November 29 at the European Charcot Foundation Symposium.

"If MS is an acquired autoimmune disease causing the immune system to mistakenly target myelin, we might be able fix that by literally purging the cells responsible and then rebuilding the immune system de novo [by autologous stem cell transplantation]," he explained. "It would then be very unlikely that the same events that occurred during childhood to build the immune repertoire would be repeated. In other words, the same mistakes won't happen twice, unless this disease is genetically driven or is a response to a persistent viral infection."

Dr. Freedman's team of researchers recruited 24 MS patients with aggressive disease and very poor prognosis who had failed on standard treatment, and eight controls.

So far, six MS patients have undergone treatment. Their stem cells were mobilised by intravenous cyclophosphamide (4.5 g/m2) and granulocyte colony stimulating factor GCSF (10 mcg/kg/day for 10 days), and collected by leukophoresis. All traces of contaminating T cells were removed by Miltenyii immunomagnetic CD 34 selection.

Immunoablation was then performed using dose-adjusted busulphan (16 mg/kg maximum total), cyclophosphamide (200 mg/kg), and rabbit anti-thymocyte globulin (5 mg/kg), and patients' were then re-infused with their purified stem cells and treated with GCSF (5 mcg/kg/day). All patients engrafted well, most within one week. Median time to platelet recovery was 10 days.

Clinical and neurological assessment was made during an ongoing follow-up (currently four to 12 months). In all patients, MS disabilities that were present prior to the transplant remained stable or improved slightly at follow-up. Remarkably, gadolinium-enhanced magnetic resonance imaging of the central nervous system showed no new MS lesions during follow-up in any patient.

Toxicity was less than expected, with no grade 3 or 4 toxicities observed, and no hepatic, pulmonary or central nervous system problems were recorded. Late complications were ovary failure in three patients and borderline gonad failure in one patient. Two cases of shingles and one of oesophageal candidiasis were observed.

"The morbidity of the treatment was much better than expected and we literally shut off disease," said Dr. Freedman.

These results also throw some light on the cause of MS. "If MS was caused by a virus in the brain eliciting a constant response by the body, you might predict that all these patients would have died when their immune system was shut down," he said.

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