Cyclophosphamide is effective in stabilizing rapidly deteriorating secondary progressive multiple sclerosis

The safety and efficacy of pulse cyclophosphamide (CTX) therapy was investigated in patients with very active secondary progressive multiple sclerosis, characterized by frequent relapses and rapid disability progression. For this purpose the clinical and MRI effects were assessed. Sixteen patients, 11 female and 5 male, were experiencing rapidly deteriorating disease, characterized by frequent and severe relapses as well as rapid progression (defined by an increase of more than 1 EDSS point in a period of 1 year). Mean relapse rate in the two years preceding CTX therapy was 3.0 +/-1.4. Mean EDSS was 4.0+/-1.4 one year before therapy and 5.6+/-1.0 at study entry. Treatment consisted in administration of high dose intravenous CTX every four weeks for one year and then every eight weeks for an additional twelve months. CTX dose was tailored to the patient's white blood cell response, and ranged from 800 to 1,200 mg/m(2) body surface. MRI was performed before therapy and then at 12 (Y1) and 24 (Y2) months. Eight patients with similar clinical features constituted a control group. CTX therapy was safe and well tolerated, and no severe side effects were observed. The EDSS decreased to 4.3+/-1.6 at Y1 (Y0 vs.Y1: p< 0.001) and to 4.1+/-1.6 at Y2 (Y0 vs.Y2: p< 0.001). Only four patients experienced relapses during the first year of therapy, while no relapses were observed during the second year of therapy. The mean relapse rate during therapy was 0.25 +/-0.45 (p< 0.0001). No increase in T2 lesion load was observed over the two years. A significant clinical and MRI deterioration was observed in the control group. Therapy with pulse CTX was able to stop disease activity and progression in patients with rapidly evolving secondary-progressive MS.