High-dose cyclophosphamide as salvage therapy for severe aplastic anemia

Objective The treatment options for patients with aplastic anemia who do not respond to conventional immunosuppression are limited. The aim of this study was to evaluate high-dose cyclophosphamide in patients with refractory severe aplastic anemia (SAA). Materials and Methods We treated 17 SAA patients with high-dose cyclophosphamide (50 mg/kg/day for 4 consecutive days) who previously did not respond to one or more courses of immunosuppressive therapy. Median age was 31 years (range 6–58); median disease duration was 14 months (range 6–58), and 8 patients met criteria for very severe aplastic anemia (absolute neutrophil count <0.2 × 109/L) at the time of treatment. Results At median follow-up of 29 months, 10 patients (59%) are alive. Nine patients (53%) achieved a drug-free remission after high-dose cyclophosphamide; 4 patients achieved a complete remission and 5 patients currently meet criteria for a partial remission but continue to improve. One nonresponder to high-dose cyclophosphamide developed paroxysmal nocturnal hemoglobinuria; another nonresponder developed a myelodysplastic syndrome. In responding patients, median time to 500 neutrophils was 54 days (range 35–119), median time to the last platelet transfusion was 99 days (range 51–751), and median time to the last red cell transfusion was 125 days (range 63–796). Conclusion High-dose cyclophosphamide shows promise for salvaging patients with refractory SAA.