Immunoablative high-dose cyclophosphamide without stem-cell rescue for refractory, severe autoimmune disease

Background: Immunoablative high-dose cyclophosphamide without stem-cell res cue induces durable, complete remission in most patients with aplastic anem ia. Objective: To determine the efficacy of high-dose cyclophosphamide in vario us refractory, severe autoimmune diseases. Design: Prospective phase II study. Setting: Johns Hopkins University (Baltimore, Maryland) and Hahnemann Unive rsity (Philadelphia, Pennsylvania). Patients: Eight patients with refractory, severe autoimmune disease. Intervention: Immunoablative high-dose cyclophosphamide (50 mg/kg of body w eight per day) for 4 consecutive days. Measurements: Clinical and laboratory variables of autoimmune disease. Results: Seven patients improved markedly: Five achieved complete remission and two achieved partial remission. Four patients have remained in continu ous complete remission for 3 to 21 months, and two patients in partial remi ssion continue to improve after 14 and 19 months of follow-up. High-dose cy clophosphamide was well tolerated; median times to a neutrophil count of 0. 5 x 10(9) cells/L and platelet transfusion independence were 17 and 16 days , respectively. Conclusions: Immunoablative high-dose cyclophosphamide without stem-cell re scue can induce complete remission in patients with refractory, severe auto immune disease. Reemergence of marrow function is similar to that seen afte r autologous transplantation and does not carry the risk for reinfusion of autoaggressive lymphocytes with the autograft.