title: Optimizing therapy for myeloid disorders of Down syndrome.
abstract: Children with Down syndrome (DS) are at increased risk of leukaemia. Myeloid disorders include transient abnormal myelopoiesis (TAM), myelodysplasia (MDS) and acute myeloid leukaemia (AML). Mutations in the GATA-1 gene, which encodes for a transcription factor central to the normal development of the erythroid and megakaryocytic lineages, are found in cases of TAM, MDS and AML in DS children. DS children with MDS/AML mostly present between the ages of 1 and 4 years, and have a large predominance of megakaryoblastic disease (French-American-British type M7). The MDS and AML are part of a single disease entity (myeloid leukaemia of Down syndrome) that is extremely sensitive to chemotherapy. Resistant disease and relapse are rare, but treatment-related toxicity is high, and deaths in remission have exceeded those due to disease in most series. Accordingly, controlled dosage reduction is the focus of contemporary treatment studies.
authors.affiliation: Department of Haematology, Great Ormond Street Hospital for Children, London, UK. david.webb@gosh.nhs.uk
authors.forename: David K H
authors.initials: DK
authors.lastname: Webb
mesh_terms: D000208:Acute Disease; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000627:therapeutic use; D002675:Child, Preschool; D004314:Down Syndrome / Q000150:complications* / Q000276:immunology / Q000628:therapy*; D004334:Drug Administration Schedule; D006801:Humans; D007223:Infant; D007951:Leukemia, Myeloid / Q000150:complications* / Q000276:immunology / Q000628:therapy*; D008533:Megakaryocytes / Q000276:immunology; D009436:Neural Tube Defects / Q000150:complications / Q000628:therapy