High Dose Cyclophosphamide for Moderate to Severe Refractory Multiple Sclerosis: 2-Year Follow-up (investigational new drug No. 65863).

High dose cyclophosphamide (HDC) is a chemotherapy treatment designed to eradicate autoreative B- and T-cells responsible for lymphocyte-mediated autoimmune illness, while sparing the pluripotent blood stem cell of any ill effects. Multiple sclerosis (MS) is the most common inflammatory and demyelinating immune-mediated disorder of the central nervous system in young adults.

Patients with moderate to severe, refractory MS, defined as an Expanded Disability Status Scale (EDSS) score of 3.5 or higher after 2 or more Food and Drug Administration-approved disease-modifying agents, received 200 mg/kg of cyclophosphamide over 4 days. For the following 2 years, quarterly EDSS score evaluations and biannual brain magnetic resonance imaging and neuro-ophthalmologic evaluations were obtained.

15 patients were evaluated for clinical response. During follow-up, no patients increased their baseline EDSS score by more than 1.0. EDSS score stability or decrease was realized in 5 of 7 (71%) patients with relapsing remitting MS and 5 of 8 (62%) patients with secondary progressive MS patients. 4 patients required additional immunomodulatory treatment after treatment. Neurologic improvement involved changes in gait, bladder control, and visual function. Treatment response was seen regardless of the baseline presence or absence of contrast lesion activity.

HDC can effectively decrease symptoms, stop disease progression, and allow for disability regression in RR and SPMS patients. The most appropriate candidates for HDC, its duration of benefit and the potential need for prophylactic preventative immune manipulation after HDC all require further investigation.

Off Label Use: cyclophosphamide: IND# 65863.