Treatment

1. Packed red cell transfusion, as required: Leukocyte-depleted packed red cells reduce the incidence of nonhemolytic, febrile transfusion reactions, as well as the risk of transmission of cytomegalovirus (CMV) and the risk of human leukocyte antigen (HLA) alloimmunization. Patients who have previously been treated with immunosuppressive drugs should receive irradiated blood products. Patients in whom stem cell transplantation is contemplated should receive CMV-negative blood products.

2. Prednisone: In a dose of 2-4 mg/kg/day given in 3 or 4 divided doses. Reticulocytosis usually occurs in 1-2 weeks but may take slightly longer. When the hemoglobin level reaches 10.0 g/dL, reduce the dose to the minimum necessary to maintain a reasonable hemoglobin level in order to obtain an effective alternate-day schedule. Any patient who experiences significant steroid-related side effects including growth failure should have steroid medication temporarily discontinued and should be placed on a red cell transfusion regimen. Patients with DBA on low-dose alternate-day therapy of long duration, starting in early infancy, may manifest significant steroid toxicity. Steroid-related side effects have been observed in most patients, with 40%, 12%, and 6.8% manifesting cushingoid features, pathologic fractures, and cataracts, respectively. It is recommended that corticosteroids be withheld for the first year of life to reduce these side effects and to allow for safe and effective immunization.

3. Hematopoietic stem cell transplantation: Although somewhat controversial, HLA-matched sibling donor transplantation should be considered for any patient with DBA. Consideration should be given to the fact that 20% of all patients attain remission, balanced by the risk of hematologic malignancy, myelodys-plasia, or severe aplastic anemia. A family marrow donor must be tested for the presence of a "silent phenotype." Matched unrelated or incompletely matched related donor transplants have proven to be very risky and should be reserved for patients with leukemia, MDS, severe aplastic anemia, or clinically significant neutropenia or thrombocytopenia.

4. Alternative therapy: A number of treatments, including erythropoietin, immunoglobulin, megadose corticosteroids, and androgens, have been utilized in DBA patients with little success. Cyclosporine, interleukin-3 (IL-3), and meto-clopramide have resulted in occasional responses in DBA. The toxicity of cyclosporine and the lack of availability of IL-3 exclude their use for most patients. A more extensive trial with metoclopramide is required to determine whether it has a place in the treatment of DBA. These agents should be explored on a case-by-case basis as an alternative to corticosteroids, transfusion, or stem cell transplantation when the risk associated with these proven modalities warrants the treatment.

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