Oral megadose methylprednisolone therapy for refractory diamond-blackfan anemia

Purpose Several reports describe children with refractory transfusion-dependent Diamond-Blackfan anemia who responded to extremely large doses of methylprednisolone. Limitations in available data prompted further exploration of this treatment approach. Patients and Methods This prospective treatment protocol was designed to test the efficacy and toxicity of oral megadose methylprednisolone in children with Diamond-Blackfan anemia who had previously failed to respond to standard doses of prednisone and who were dependent on regular packed red blood cell transfusions. Patients were treated with oral methylprednisolone, starting at a dose of 100 mg/kg per day, tapering slowly to 5 mg/kg per day at the end of 4 weeks and to 2 mg/kg per day after 7 weeks of induction therapy. Therapy was continued for a total of 23 weeks. Efficacy was assessed by increase in peripheral blood reticulocytes and increase or stabilization in hemoglobin concentration, which was maintained during and after steroid tapering. Results Nine children with Diamond-Blackfan anemia were registered on the study, and all were evaluable. Disease in four of the children failed to respond to megadose methylprednisolone therapy. The other five patients demonstrated a partial or complete response during the initial 4 to 8 weeks of therapy, but all subsequently experienced relapse during the ensuing 2 months as the corticosteroid dose was tapered. All patients required resumption of transfusions, although one later remitted spontaneously. Toxicity of megadose methylprednisolone was modest. Conclusion None of nine children with refractory Diamond-Blackfan anemia treated with oral megadose methylprednisolone exhibited a clinically significant response. Alternative therapeutic strategies are required.