Clinical Analysis of Diamond-Blackfan Anemia

Abstract

Objective To explore the clinical characteristics,diagnosis and treatment of DiamondBlacken Anemia (DBA).Methods From July 2003 to July 2013,a total of 61 children diagnosed as DBA in Diagnosis and Treatment Center of Pediatric Blood Diseases,Institute of Hematology and Blood Diseases Hospital,Peking Union Medical College,Chinese Academy of Medical Sciences were collected into this study.Clinical data of DBA children were retrospectively analyzed.The study protocol was approved by the Ethical Review Board of Investigation in Human at Institute of Hematology and Blood Diseases Hospital,Peking Union Medical College,Chinese Academy of Medical Sciences.Informed consent was obtained from all participants' parents.Blood specimens from 61 children were collected at Diagnosis and Treatment Center of Pediatric Blood Diseases.Erythroid colony forming unit (CFU-E) and erythroid burst forming unit (BFU-E) were counted by colony-forming cell (CFC) test in 26 children.Eighteen children received targeted exon capture sequencing of 9 ribosome protein genes.Response rates to glucocorticoid were compared between children with low BFU-E/CFU-E and children with non-low BFU-E/CFU-E,and were compared between children with positive ribosome protein genes mutation and children with negative mutation.Results ① Median age of onset of 61 children was 3 months old (0～39 months old).Fifteen(24.5％)cases had physical malformation.② Median hemoglobin (Hb) level of 61 children at first visit was 49 g/L (15～80 g/L).Median red blood cell count was 2.15 × 1012/L.Median mean corpuscular volume (MCV) was 87.3 fl (69.0～105.0 fl).Erythrogenin (EPO) level increased in 90.5％ (19/21) children.Median bone marrow erythroid proportion was 2％ (0～ 17.5％) in 42 children who got bone marrow puncture.50.0％ (13/26) children had low BFU-E and CFU-E,while 23.0％ (6/26) were normal,and 26.9％ (7/26) had high BFU-E and CFU-E.③ Eighteen children received targeted exon capture sequencing of 9 ribosome protein genes protein genes.50.0％ (9/18)cases were ribosome protein genes mutation positive.RPS19 mutation occurred in 5 cases(27.8％),and RPL11,RPL5,RPL35a and RPS7 mutation occurred in one case(5.6％) respectively.44.4％ (4/9) cases had physical malformation,and 22.2％ (2/9) cases suffered from growth retardation.④Fifty children received prednisone therapy.64.0％ (32/50) children responded to prednisone,and 15 children got remission.20 children who didn't respond to prednisone or didn't get remission were treated with cyclosporin A,and 2 children got remission.After treatment of prednisone,cyclosporin A or allogeneic hematopoietic stem cell transplantation (allo-HSCT),33.9％ (19/56)children were in remission during follow-up,and 5.4％ (3/56) children died.Response rate to glucocorticoid was lower in children with low BFU-E/CFU-E (54.5％,6/11) than that in children with non-low BFU-E/CFU-E (66.7 ％,6/9),though without statistical differences (P =0.425).Children with positive ribosome protein genes mutation group (77.8％,7/9) had higher response rate to glucocorticoid compared to children with negative mutation (55.6％,5/9),though without statistical differences neither (P=0.342).Conclusions The majority of onset age of DBA children were within 1 year old.About 25％ children had physical malformation.EPO level,CFC test and ribosome protein gene mutation could guide diagnosis,treatment and prognosis of DBA.Glucocorticoid was preferred treatment of DBA.Blood infusion and allo-HSCT were also effective treatment. Key words: Anemia, Diamond-Blackfan; Erythoid cells; Child; Ribosome proteins