Diamond-Blackfan anemia. Natural history and sequelae of treatment

To define further the natural history of treated Diamond-Blackfan anemia (DBA), a congenital anemia characterized by a paucity of erythroid precursors, we analyzed 76 patients diagnosed or followed at Children's Hospital, Boston, between 1931 and 1992. Although DBA is generally defined as macrocytic, we found that mean corpuscular volume in infants aged <5 months rarely exceeded the normal range and is of little diagnostic value. Macrocytosis in patients aged > or = 5 months was more striking. Nine of 16 patients who never received steroids experienced remissions, sometimes after years of transfusions. Thirty-one of 56 patients receiving corticosteroids responded. Of these 31, 13 experienced remissions, 11 remained steroid dependent and 7 later required transfusions. Most nonresponders maintained transfusion dependence. Patients frequently (64%) experienced treatment-related morbidity, most commonly hemosiderosis. The relative risk of leukemia was profoundly elevated (RR, 200; 95% CI, 54.5-512.1) and hematologic parameters at long-term follow-up were often abnormal. While potential responsiveness to steroids and relative ease of red cell transfusion make DBA one of the most treatable congenital marrow failure syndromes, both disease-related and treatment-related factors contributed to a limited prognosis (median survival, 38 years). Patients should be carefully monitored longitudinally for evidence of leukemia and adverse effects of therapy, and alternative treatment strategies should be considered on an individual basis.