Abstract
Diamond Blackfan anemia (DBA) is an inherited bone marrow failure syndrome characterized by red cell aplasia and congenital anomalies. A predisposition to cancer has been suggested but not quantified by case reports. The DBA Registry of North America (DBAR) is the largest established DBA patient cohort, with prospective follow-up since 1991. This report presents the first quantitative assessment of cancer incidence in DBA. Among 608 patients with 9458 person-years of follow-up, 15 solid tumors, 2 acute myeloid leukemias, and 2 cases of myelodysplastic syndrome were diagnosed at a median age of 41 years in patients who had not received a bone marrow transplant. Cancer incidence in DBA was significantly elevated. The observed-to- expected ratio for all cancers combined was 5.4 (P < .05); significant observed-to-expected ratios were 287 for myelodysplastic syndrome, 28 for acute myeloid leukemia, 36 for colon carcinoma, 33 for osteogenic sarcoma, and 12 for female genital cancers. The median survival was 56 years, and the cumulative incidence of solid tumor/leukemia was approximately 20% by age 46 years. As in Fanconi anemia and dyskeratosis congenita, DBA is both an inherited bone marrow failure syndrome and a cancer predisposition syndrome; cancer risks appear lower in DBA than in Fanconi anemia or dyskeratosis congenita. This trial was registered at www.clinicaltrials.gov as #NCT00106015.