Durable treatment-free remission after high-dose cyclophosphamide therapy for previously untreated severe aplastic anemia

Background: severe aplastic anemia is a life-threatening bone marrow failur e disorder. High-dose cyclophosphamide therapy followed by allogeneic bone marrow transplantation cures the disease. However, it requires a suitable d onor and carries the risk for graft-versus-host disease. A small pilot stud y demonstrated that high-dose cyclophosphamide therapy without bone marrow transplantation leads to durable, treatment-free complete remission. Objective: To confirm the safety and efficacy of high-dose cyclophosphamide therapy alone in patients with severe aplastic anemia. Design: Uncontrolled clinical trial. Setting: Three tertiary care hospitals. Patients: 19 patients with untreated severe aplastic anemia. Intervention: Cyclophosphamide, 50 mg/kg of body weight per day for 4 conse cutive days. Measurements: Probability of response and overall survival were measured. C omplete remission was defined as normal blood count for age and sex. Partia l remission was defined as independence from transfusion and an absolute ne utrophil count greater than 0.5 x 10(9) cells/L without growth factor suppo rt. Nonresponders were patients who remained transfusion dependent or died. Relapse was defined as no longer meeting criteria for partial or complete remission. Results: The median time to an absolute neutrophil count of 0.5 x 109 cells /L was 49 days. The probability of survival was 84% (95% Cl, 59% to 95%) at 24 months. The probability of achieving treatment-free remission was 73% ( Cl, 51% to 91%) at 24 months, and the probability of achieving complete rem ission was 65% (Cl, 39% to 89%) at 50 months. No responding patients have h ad relapse or have developed secondary clonal disorders. Conclusions: High-dose cyclophosphamide therapy without bone marrow transpl antation produces durable treatment-free remission in severe aplastic anemi a. This approach deserves further study in patients with severe aplastic an emia who are not suitable candidates for allogeneic bone marrow transplanta tion.