title: Outcome heterogeneity in childhood high-hyperdiploid acute lymphoblastic leukemia.
abstract: High hyperdiploidy (HeH) (51 to 65 chromosomes) is found in one third of children with acute lymphoblastic leukemia and is associated with a good prognosis. Cytogenetic features may further refine this prognosis and identify patients with a poor outcome. We examined the effect of sex, age, individual trisomies, modal number, and structural abnormalities on survival among 700 children with HeH. Univariate analysis showed that age. sex, +4, +10, +18, and a high modal number were associated with survival. Multivariate analysis however, revealed that only age, sex, +4, and +18 were independent indicators. Hazard scores for predicting relapse and mortality were constructed. Three risk groups with 5-year event-free survival (EFS) rates of 86%, 75%, and 50% (P <.0001) were identified. The high-risk group comprised boys older than 9 years, boys aged 1 through 9 years without +18, and girls older than 9 years without +18, while girls aged 1 through 9 years with +18 had the best EFS. In terms of mortality, those younger than age 10 years with both +4 and +18 had an improved survival (96% vs 84% at 5 years, P <.0001). These findings confirm that the outcome of children with HeH is heterogeneous and that specific trisomies can identify patients with the greatest and least risk of treatment failure.
authors.affiliation: Leukaemia Research Fund Cytogenetics Group, Cancer Sciences Division, University of Southampton, MP 822, Duthie Bldg, Southampton General Hospital, Southampton, SO16 6YD, United Kingdom. avm@soton.ac.uk
authors.forename: Anthony V
authors.initials: AV
authors.lastname: Moorman
authors.forename: Sue M
authors.initials: SM
authors.lastname: Richards
authors.forename: Mary
authors.initials: M
authors.lastname: Martineau
authors.forename: Kan Luk
authors.initials: KL
authors.lastname: Cheung
authors.forename: Hazel M
authors.initials: HM
authors.lastname: Robinson
authors.forename: G Reza
authors.initials: GR
authors.lastname: Jalali
authors.forename: Zoe J
authors.initials: ZJ
authors.lastname: Broadfield
authors.forename: Rachel L
authors.initials: RL
authors.lastname: Harris
authors.forename: Kerry E
authors.initials: KE
authors.lastname: Taylor
authors.forename: Brenda E S
authors.initials: BE
authors.lastname: Gibson
authors.forename: Ian M
authors.initials: IM
authors.lastname: Hann
authors.forename: Frank G H
authors.initials: FG
authors.lastname: Hill
authors.forename: Sally E
authors.initials: SE
authors.lastname: Kinsey
authors.forename: Tim O B
authors.initials: TO
authors.lastname: Eden
authors.forename: Christopher D
authors.initials: CD
authors.lastname: Mitchell
authors.forename: Christine J
authors.initials: CJ
authors.lastname: Harrison
mesh_terms: D000293:Adolescent; D000367:Age Factors; D002648:Child; D002675:Child, Preschool; D004171:Diploidy; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D007223:Infant; D007621:Karyotyping; D008297:Male; D015999:Multivariate Analysis; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000188:drug therapy* / Q000235:genetics* / Q000401:mortality; D011379:Prognosis; D016016:Proportional Hazards Models; D012737:Sex Factors; D013997:Time Factors; D016896:Treatment Outcome; D014314:Trisomy