High-dose cyclophosphamide is safe and well-tolerated for aggressive multiple sclerosis, according to the results of a small, open-label trial.

High-dose cyclophosphamide, aimed at immune system ablation, is a safe and well-tolerated treatment for aggressive multiple sclerosis that can markedly reduce disease activity and disability, according to the results of a small, open-label trial.

In an earlier study of 13 patients with severe refractory multiple sclerosis, treatment with high-dose cyclophosphamide followed by granulocyte colony-stimulating factor often stabilized or improved disability. The current study investigated the safety and efficacy of this treatment further by examining clinical and radiologic features not previously studied and by including a longer follow-up period.

As reported in the August issue of the Archives of Neurology, Dr. Douglas A. Kerr and colleagues focused on the safety and tolerability of high-dose cyclophosphamide in nine patients (20 to 47 years of age) with aggressive relapsing-remitting multiple sclerosis. Clinical and radiologic efficacy endpoints were secondary outcomes.

Eight of the patients were unresponsive to conventional therapy and one patient was treatment naive. Cyclophosphamide was given at a dose of 50 mg/kg/day intravenously for four days. Granulocyte colony-stimulating factor was then started six days later, given at a dose of five micrograms/kg/day until the absolute neutrophil count was over one billion cells/L for two consecutive days.

During a mean follow-up period of 23 months, none of the patients died and there were no unexpected adverse events, Dr. Kerr, from Johns Hopkins University School of Medicine in Baltimore, and co-researchers report. As anticipated, all of the patients developed total or near-total pancytopenia, but hematopoietic recovery was achieved ten to 17 days later with the use of granulocyte colony-stimulating factor.

High-dose cyclophosphamide therapy resulted in significant reductions in the Expanded Disability Status Scale score (39.4 per cent) and in the average number of gadolinium-enhancing lesions on MRI (81.4 per cent).

Due to disease flare-ups, two patients required treatment with other immunomodulatory therapies during the study, the authors note.

"This immunoablative regimen of cyclophosphamide for patients with aggressive multiple sclerosis is worthy of further study and may be an alternative to bone marrow transplantation," the team concludes.

Arch Neurol 2008;65:1044-1051