title: Down syndrome childhood acute lymphoblastic leukemia has a unique spectrum of sentinel cytogenetic lesions that influences treatment outcome: a report from the Children's Oncology Group.
abstract: Children with Down syndrome (DS) have an increased risk of acute lymphoblastic leukemia (ALL) and an inferior outcome. We reviewed data from 2811 children with ALL enrolled in Children's Oncology Group P9900, which included prospective testing for the major cytogenetic lesions in childhood ALL: ETV6-RUNX1, TCF3-PBX1, BCR-ABL1, and MLL translocations and trisomies of chromosomes 4 and 10. Eighty (3%) B-precursor ALL patients had DS. Age, sex, white blood cell count, and risk group were similar between DS-ALL and non-DS-ALL but significantly more patients with DS-ALL were white (91.2% vs 76.4%, P = .001). Children with DS-ALL had lower rates of the favorable cytogenetic lesions ETV6-RUNX1 (2.5% vs 24%, P < .001) and trisomies 4 and 10 (7.7% vs 24%, P < .001). Five-year event-free (EFS) and overall survival (OS) were inferior in children with DS-ALL: 69.9% +/- 8.6% versus 78.1% +/- 1.2% (P = .078), and 85.8% +/- 6.5% versus 90.0% +/- 0.9% (P = .033). However, when children with MLL translocations, BCR-ABL1, ETV6-RUNX1, and trisomies 4 and 10 were excluded, the EFS and OS were similar for children with and without DS (EFS 68.0 %+/- 9.3% vs 70.5% +/- 1.9%, P = .817; and OS 86.7% +/- 6.7% vs 85.4% +/- 1.5%; P = .852), both overall and adjusted for race. DS-ALL displays a unique spectrum of biologic subtypes with different frequencies of sentinel cytogenetic lesions having a large influence on outcome.
authors.affiliation: University of Colorado Denver School of Medicine and the Children's Hospital, 13123 E 16th Ave., Aurora, CO 80045, USA. Maloney.kelly@tchden.org
authors.forename: Kelly W
authors.initials: KW
authors.lastname: Maloney
authors.forename: William L
authors.initials: WL
authors.lastname: Carroll
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Carroll
authors.forename: Meenakshi
authors.initials: M
authors.lastname: Devidas
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Borowitz
authors.forename: Paul L
authors.initials: PL
authors.lastname: Martin
authors.forename: Jeanette
authors.initials: J
authors.lastname: Pullen
authors.forename: James A
authors.initials: JA
authors.lastname: Whitlock
authors.forename: Cheryl L
authors.initials: CL
authors.lastname: Willman
authors.forename: Naomi J
authors.initials: NJ
authors.lastname: Winick
authors.forename: Bruce M
authors.initials: BM
authors.lastname: Camitta
authors.forename: Stephen P
authors.initials: SP
authors.lastname: Hunger
mesh_terms: D002648:Child; D002869:Chromosome Aberrations; D002879:Chromosomes, Human, Pair 10 / Q000235:genetics; D002894:Chromosomes, Human, Pair 4 / Q000235:genetics; D050676:Core Binding Factor Alpha 2 Subunit; D004314:Down Syndrome / Q000235:genetics* / Q000628:therapy; D005260:Female; D016044:Fusion Proteins, bcr-abl / Q000235:genetics; D011495:Histone-Lysine N-Methyltransferase; D006801:Humans; D008297:Male; D051788:Myeloid-Lymphoid Leukemia Protein / Q000235:genetics; D018365:Neoplasm, Residual / Q000175:diagnosis; D015514:Oncogene Proteins, Fusion / Q000235:genetics; D016133:Polymerase Chain Reaction; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000235:genetics* / Q000473:pathology / Q000628:therapy; D011446:Prospective Studies; D015996:Survival Rate; D016896:Treatment Outcome; D014314:Trisomy; D000097764:ETS Translocation Variant 6 Protein
chemical_list: D050676:Core Binding Factor Alpha 2 Subunit; D016044:Fusion Proteins, bcr-abl; D011495:Histone-Lysine N-Methyltransferase; D051788:Myeloid-Lymphoid Leukemia Protein; D015514:Oncogene Proteins, Fusion; C497422:KMT2A protein, human; C543638:TCF3-PBX1 fusion protein, human; C102421:TEL-AML1 fusion protein; D000097764:ETS Translocation Variant 6 Protein