title: Secondary cytogenetic aberrations in childhood Philadelphia chromosome positive acute lymphoblastic leukemia are nonrandom and may be associated with outcome.
abstract: Additional chromosomal aberrations occur frequently in Philadelphia chromosome positive (Ph+) acute lymphoblastic leukemia (ALL) of childhood. The treatment outcome of these patients is heterogeneous. This study assessed whether such clinical heterogeneity could be partially explained by the presence and characteristics of additional chromosomal abnormalities. Cytogenetic descriptions were available for 249 of 326 children with Ph+ ALL, diagnosed and treated by 10 different study groups/large single institutions from 1986 to 1996. Secondary aberrations were present in 61% of the cases. Chromosomes 9, 22, 7, 14, and 8 were most frequently abnormal. Most (93%) karyotypes were unbalanced. Three main cytogenetic subgroups were identified: no secondary aberrations, gain of a second Ph and/or >50 chromosomes, or loss of chromosome 7, 7p, and/or 9p, while other secondary aberrations were grouped as combinations of gain and loss or others. Of the three main cytogenetic subgroups, the loss group had the worst event-free survival (P=0.124) and disease-free survival (P=0.013). However, statistical significance was not maintained when adjusted for other prognostic factors and treatment. Karyotypic analysis is valuable in subsets of patients identified by molecular screening, to assess the role of additional chromosomal abnormalities and their correlation with clinical heterogeneity, with possible therapeutic implications.
authors.affiliation: Department of Pathology, The Ohio State University, Columbus, OH 43210, USA. heerema-1@medctr.osu.edu
authors.forename: N A
authors.initials: NA
authors.lastname: Heerema
authors.forename: J
authors.initials: J
authors.lastname: Harbott
authors.forename: S
authors.initials: S
authors.lastname: Galimberti
authors.forename: B M
authors.initials: BM
authors.lastname: Camitta
authors.forename: P S
authors.initials: PS
authors.lastname: Gaynon
authors.forename: G
authors.initials: G
authors.lastname: Janka-Schaub
authors.forename: W
authors.initials: W
authors.lastname: Kamps
authors.forename: G
authors.initials: G
authors.lastname: Basso
authors.forename: C-H
authors.initials: CH
authors.lastname: Pui
authors.forename: M
authors.initials: M
authors.lastname: Schrappe
authors.forename: M-F
authors.initials: MF
authors.lastname: Auclerc
authors.forename: A J
authors.initials: AJ
authors.lastname: Carroll
authors.forename: V
authors.initials: V
authors.lastname: Conter
authors.forename: C J
authors.initials: CJ
authors.lastname: Harrison
authors.forename: J
authors.initials: J
authors.lastname: Pullen
authors.forename: S C
authors.initials: SC
authors.lastname: Raimondi
authors.forename: S
authors.initials: S
authors.lastname: Richards
authors.forename: H
authors.initials: H
authors.lastname: Riehm
authors.forename: H N
authors.initials: HN
authors.lastname: Sather
authors.forename: J J
authors.initials: JJ
authors.lastname: Shuster
authors.forename: L B
authors.initials: LB
authors.lastname: Silverman
authors.forename: M G
authors.initials: MG
authors.lastname: Valsecchi
authors.forename: M
authors.initials: M
authors.lastname: Aricò
mesh_terms: D002648:Child; D002869:Chromosome Aberrations; D019457:Chromosome Breakage; D002872:Chromosome Deletion; D020732:Cytogenetic Analysis; D018572:Disease-Free Survival; D005260:Female; D018740:Genetic Heterogeneity; D006801:Humans; D016013:Likelihood Functions; D008297:Male; D010677:Philadelphia Chromosome; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000175:diagnosis / Q000235:genetics* / Q000401:mortality; D011379:Prognosis; D016019:Survival Analysis; D016896:Treatment Outcome