Cyclophosphamide for severe acute forms of central nervous system inflammatory disorders.

Cyclophosphamide (CYC) may be an effective treatment in patients who fail first line therapy for severe central nervous system (CNS) inflammatory disorders including CNS vasculitis, neuromyelitis optica, autoimmune encephalitis, tumefactive and aggressive multiple sclerosis (MS). We performed a retrospective analysis of 46 patients treated with CYC after failing first line therapy for severe CNS inflammatory conditions. Primary outcomes included modified Rankin Scale (mRS) for patients classified into a non-MS group, Expanded Disability Status Score (EDSS) for MS patients, and Targeted Neurological Deficit score (TND) for all patients. Secondary outcome included neuroimaging studies following CYC treatment. By the second follow up period (average of 7 months) mRS in the non-MS group improved from 3.7 to 2.2 and EDSS in the MS group improved from 5.6 to 3.8. Average TND score at 7 months was 2.8 (mild-marked improvement). At first follow up (average 5.6 months), 76.2% (32/42) patients had either stable or improving imaging, and 83.3% (30/36) patients had stable or improving imaging at second follow up (average 13.6 months). Adverse events were reported by 31.9% of patients with most common being nausea and vomiting, headache, alopecia, and hyponatremia. Treatment with CYC can result in disease stabilization of severe CNS inflammatory diseases and is generally well tolerated.

Risk factors for lymphopenia in patients with relapsing-remitting multiple sclerosis treated with dimethyl fumarate.

OBJECTIVES: To identify risk factors for DMF-induced lymphopenia and characterize its impact on T lymphocyte subsets in MS patients. METHODS: We performed a retrospective analysis of 194 RRMS patients treated with DMF at the Beth Israel Deaconess Medical Center (BIDMC) over a median of 17 months. We reviewed demographics, ethnic background, prior medication history, complete blood counts and T lymphocyte subsets. Possible lymphopenia risk factors examined included age, prior natalizumab exposure, vitamin D levels, and concomitant exposure to carbamazepine, opiates, tobacco, or steroids. Lymphopenia was defined as grade 1: absolute lymphocytes count (ALC) 800-999/µl; grade 2: ALC 500-799/µl; grade 3: ALC 200-499/µl; and grade 4: ALC < 200/µl. RESULTS: Of 194 DMF-treated patients, 73 (38%) developed lymphopenia and reached an ALC nadir after a median of 504 days (range 82-932). Risk of developing DMF-induced lymphopenia increased with BMI 25-30, older age, white ethnicity, non-smoking status, and lowest quartile baseline ALC. Prior exposure to natalizumab or concomitant steroid, opiates or carbamazepine/oxcarbamazepine use was not associated with lymphopenia. Compared to baseline levels, CD8 T cells were significantly more reduced than CD4 cells. CD8 counts were more commonly reduced with age or white ethnicity. Subjects with BMI 25-30 was associated with a higher risk of abnormal CD4 cell count reductions. In contrast, non-smokers were more likely to experience reductions in both CD4 and CD8 counts while on DMF. CONCLUSIONS: Patients with low baseline lymphocyte counts, with intermediate BMI, with white ethnicity, with advanced age, or with no tobacco use, had a significantly higher incidence of lymphopenia on DMF. Intermediate BMI or lowest quartile baseline ALC predicted low CD4 levels, while advanced age or white ethnicity predicted low CD8 levels from DMF exposure.