title: Association of chromosome arm 9p abnormalities with adverse risk in childhood acute lymphoblastic leukemia: A report from the Children's Cancer Group.
abstract: Cytogenetic abnormalities of chromosome arm 9p occur frequently in children with acute lymphoblastic leukemia (ALL). We analyzed 201 such cases (11%) in 1,839 children with newly diagnosed ALL treated between 1989 and 1995 on risk-adjusted protocols of the Children's Cancer Group (CCG). The majority of patients (131; 65%) with a 9p abnormality were classified as higher risk. Nearly all patients had complex karyotypes; most cases had deletions of 9p, add/der(9p), a dicentric involving chromosome arm 9p, and/or balanced translocations and inversions involving 9p. Event-free survival (EFS) estimates at 6 years for patients with and without a 9p aberration were 61% (standard deviation [SD] = 5%) and 76% (SD = 2%; P <.0001). In addition, patients with a 9p abnormality had an increased cumulative incidence of both marrow (P =.04) and central nervous system (P =.0001) relapses. Overall survival also was significantly worse for patients with an abnormal 9p (P <.0001). These effects were most pronounced in standard-risk patients (age 1 to 9 years with white blood cell count <50,000/microL): 6-year EFS of 61% (SD = 9%) versus 80% (SD = 2%; P <.0001). Also, a 9p aberration was an adverse risk factor for B-lineage, but not T-lineage patients. The effect of 9p status on EFS was attenuated, but maintained in a multivariate analysis of EFS after adjustment for Philadelphia chromosome status, age, white blood cell (WBC) count, sex, race, and ploidy group (P =.01). Thus, abnormalities of chromosome arm 9p identify a subgroup of standard-risk patients with increased risk of treatment failure.
authors.affiliation: Department of Genetics, Hughes Institute, St Paul, MN, USA.
authors.forename: N A
authors.initials: NA
authors.lastname: Heerema
authors.forename: H N
authors.initials: HN
authors.lastname: Sather
authors.forename: M G
authors.initials: MG
authors.lastname: Sensel
authors.forename: W
authors.initials: W
authors.lastname: Liu-Mares
authors.forename: B J
authors.initials: BJ
authors.lastname: Lange
authors.forename: B C
authors.initials: BC
authors.lastname: Bostrom
authors.forename: J B
authors.initials: JB
authors.lastname: Nachman
authors.forename: P G
authors.initials: PG
authors.lastname: Steinherz
authors.forename: R
authors.initials: R
authors.lastname: Hutchinson
authors.forename: P S
authors.initials: PS
authors.lastname: Gaynon
authors.forename: D C
authors.initials: DC
authors.lastname: Arthur
authors.forename: F M
authors.initials: FM
authors.lastname: Uckun
mesh_terms: D002648:Child; D002675:Child, Preschool; D002869:Chromosome Aberrations; D002899:Chromosomes, Human, Pair 9; D005260:Female; D006801:Humans; D007223:Infant; D008297:Male; D015999:Multivariate Analysis; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000235:genetics* / Q000503:physiopathology; D012307:Risk Factors