Effectiveness of subcutaneous low-dose alemtuzumab and rituximab combination therapy for steroid-resistant chronic graft-versus-host disease.

BACKGROUND: Chronic graft-versus-host disease is a common late complication of allogeneic hematopoietic stem cell transplantation. Corticosteroids are the standard initial treatment. Second-line treatment has not been well defined. We evaluated the effectiveness and safety of low doses of alemtuzumab plus low doses of rituximab in the treatment of steroid-refractory chronic graft-versus-host disease. DESIGN AND METHODS: Ten men and 5 women were prospectively included in the study. All patients received one cycle of subcutaneous alemtuzumab 10 mg/day/3 days and intravenous rituximab 100 mg on Days +4, +11, +18 and +25. The therapeutic response was measured on Days +30, +90 and +365 of the protocol. RESULTS: Median age was 41 years. The main site involved was the oral mucosa (86.7%) followed by the eyes (66.7%), liver (60%), skin (53%), lungs (13.3%) and intestinal tract (6.7%). The overall response was 100% at Day +30 evaluation: 10 patients (67%) had partial remission, 5 (33%) had complete remission. At Day +90 evaluation, 7 (50%) patients had partial remission, 4 (28%) had complete remission; 3 (21%) had relapsed chronic graft-versus-host disease and one patient did not reach the evaluation time point. So far, 5 patients have reached the Day +365 follow-up evaluation; 2 (40%) had partial remission, 2 had complete remission and one experienced chronic graft-versus-host disease progression. Adverse effects were mainly infections in 67% of patients; these were all quickly solved, except for one patient who died from pneumonia. CONCLUSIONS: This combination therapy appears to be an efficacious and safe treatment for steroid-refractory chronic graft-versus-host disease. Longer follow up to determine the durability of response and survival is required (ClinicalTrials.gov: NCT01042509).

Topiramate as an adjunctive treatment in migraine prophylaxis.

BACKGROUND: Anticonvulsants now are commonly used for headache prevention. Topiramate, one of the newer anticonvulsants, recently has been demonstrated to be effective as monotherapy for migraine prophylaxis. OBJECTIVE: To assess the efficacy, safety, and tolerability of topiramate as adjunctive prophylactic therapy for migraine. MATERIAL AND METHODS: A prospective trial involving patients with more than 3 migraine attacks per month was performed. Patients continued their usual prophylactic treatment. Baseline analgesic use and frequency and duration of migraine attacks were recorded. A 4-point visual analog scale evaluated severity. Laboratory tests, electrocardiogram, and computed tomography or magnetic resonance imaging were performed before study entry. After informed consent was obtained, patients were instructed to take 25 mg of topiramate per day, with 25- to 50-mg weekly increments to a maximum of 100 mg per day. Safety was assessed at the first month; tolerability and efficacy were assessed every week for the first month and then every month for 3 months. Effectiveness was assessed by comparing baseline and on-treatment migraine status, and data were analyzed by the Fisher exact test. RESULTS: Twenty-five women and 11 men (mean age, 44 years) were evaluated. Existing prophylactic treatment was either propranolol or flunarizine (or both) in 80% of the patients. At 3 months of therapy with topiramate, headache frequency decreased from 17 to 3 episodes per month, headache duration from 559 to 32 minutes, and intensity from 9 to 1 by visual analog scale (P <.001). Improvement in frequency and severity of migraine was observed in 83% of patients. Slight or no changes in headache were observed in 6 patients. Tolerability was good in 30 patients. The most common side effects were acroparesthesias, weight loss, sleepiness, and headache worsening. No adverse interaction with propranolol or flunarizine was observed. CONCLUSIONS: These results suggest that topiramate is efficacious and safe as an adjunctive treatment in patients with migraine whose prior response to prophylactic management has been less than satisfactory.