title: Treatment for myeloid leukaemia of Down syndrome: population-based experience in the UK and results from the Medical Research Council AML 10 and AML 12 trials.
abstract: Down syndrome (DS) children are at an increased risk of developing myelodysplasia and acute myeloid leukaemia (AML). We retrospectively analysed the population-based data on 81 children with myeloid leukaemia of Down syndrome (ML-DS) from the UK National Registry of Childhood Tumours and experience in the Medical Research Council (MRC) AML 10 and AML 12 trials, which enrolled 46 children with ML-DS from 1988 to 2002. Eight per cent of UK children with AML had DS, but DS children comprised only 5% of children registered in MRC trials. The unique clinical characteristics of ML-DS were confirmed. Overall survival (OS) of ML-DS at 5 years increased from 47% in UK children diagnosed from 1988 to 1995 to 75% in children diagnosed from 1996 to 2002. OS for DS children registered in AML 10 and AML 12 was 74% in 5 years and improved from AML 10 to AML 12 (56% vs. 83%) There was no significant difference in OS between DS and non-DS children (OS: 74% vs. 62%, P = 0.4) in the trials, but this result masked a significant increase in early death amongst DS children, with a significant reduction in mortality later on. Relapse was significantly reduced (3% vs. 39%, P = 0.0003), leading to the improved disease-free survival (83% vs. 56%, P = 0.02). Given the increased number of early treatment-related deaths, future treatment protocols should aim to reduce chemotherapy dosage or intensity whilst maintaining low rates of resistant and recurrent disease.
authors.affiliation: Department of Haematology, Camelia Botnar Laboratories, Great Ormond Street Hospital for Children, London, UK. raoa@gosh.nhs.uk
authors.forename: Anupama
authors.initials: A
authors.lastname: Rao
authors.forename: Robert K
authors.initials: RK
authors.lastname: Hills
authors.forename: Charles
authors.initials: C
authors.lastname: Stiller
authors.forename: Brenda E
authors.initials: BE
authors.lastname: Gibson
authors.forename: Siebold S N
authors.initials: SS
authors.lastname: de Graaf
authors.forename: Ian M
authors.initials: IM
authors.lastname: Hann
authors.forename: Aengus
authors.initials: A
authors.lastname: O'Marcaigh
authors.forename: Keith
authors.initials: K
authors.lastname: Wheatley
authors.forename: David K H
authors.initials: DK
authors.lastname: Webb
mesh_terms: D000293:Adolescent; D000677:Amsacrine / Q000008:administration & dosage; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D002648:Child; D002675:Child, Preschool; D003561:Cytarabine / Q000008:administration & dosage; D020732:Cytogenetic Analysis; D003630:Daunorubicin / Q000008:administration & dosage; D004314:Down Syndrome / Q000150:complications* / Q000188:drug therapy* / Q000401:mortality; D004334:Drug Administration Schedule; D005047:Etoposide / Q000008:administration & dosage; D005260:Female; D006801:Humans; D007223:Infant; D007951:Leukemia, Myeloid / Q000150:complications* / Q000188:drug therapy* / Q000401:mortality; D007958:Leukocyte Count; D008297:Male; D008942:Mitoxantrone / Q000008:administration & dosage; D013866:Thioguanine / Q000008:administration & dosage; D016896:Treatment Outcome; D006113:United Kingdom
chemical_list: D000677:Amsacrine; D003561:Cytarabine; D005047:Etoposide; D008942:Mitoxantrone; D013866:Thioguanine; D003630:Daunorubicin