title: Clinical and cytogenetic features of a population-based consecutive series of 285 pediatric T-cell acute lymphoblastic leukemias: rare T-cell receptor gene rearrangements are associated with poor outcome.
abstract: Clinical characteristics and cytogenetic aberrations were ascertained and reviewed in a population-based consecutive series of 285 pediatric T-cell acute lymphoblastic leukemias (T-ALLs) diagnosed between 1992 and 2006 in the Nordic countries. Informative karyotypic results were obtained in 249 (87%) cases, of which 119 (48%) were cytogenetically abnormal. Most (62%) of the aberrant T-ALLs were pseudodiploid. Structural changes were more common than numerical ones; 86% displayed at least one structural abnormality and 41% at least one numerical anomaly. The most frequent abnormalities were T-cell receptor (TCR) gene rearrangements (20%) [TCR;11p13 (10%), TCR;10q24 (3%), TCR;other (8%)], del(9p) (17%), +8 (14%), del(6q) (12%), and 11q23 rearrangements (6%). The TCR;other group comprised the rare rearrangements t(X;14)(p11;q11), t(X;7)(q22;q34), t(1;14)(p32;q11), ins(14;5)(q11;q?q?), inv(7)(p15q34), t(8;14)(q24;q11), t(7;11)(q34;p15), and t(12;14)(p13;q11). The clinical characteristics of this Nordic patient cohort agreed well with previous larger series, with a median age of 9.0 years, male predominance (male/female ratio 3.1), median white blood cell (WBC) count of 66.5 x 10(9)/l, and a high incidence of mediastinal mass and central nervous system involvement (59% and 9.5%, respectively). These features did not differ significantly among the various genetic subgroups. 5-year event-free survival (EFS) and overall survival for all patients were 0.61 (+/-0.03) and 0.67 (+/-0.03), respectively. In a multivariate analysis, two factors affected negatively the EFS, namely a WBC count of > or =200 x 10(9)/l (P < 0.001) and the presence of rare TCR rearrangements (P = 0.001). In conclusion, in this large series of childhood T-ALLs from the Nordic countries, the cytogenetic findings were not associated with risk of therapy failure with the exception of the TCR;other group. However, further prospective and collaborative investigations of this genetically heterogeneous entity are needed to confirm these results.
authors.affiliation: Department of Clinical Genetics, Lund University Hospital, Lund, Sweden. kristina.karrman@med.lu.se
authors.forename: Kristina
authors.initials: K
authors.lastname: Karrman
authors.forename: Erik
authors.initials: E
authors.lastname: Forestier
authors.forename: Mats
authors.initials: M
authors.lastname: Heyman
authors.forename: Mette K
authors.initials: MK
authors.lastname: Andersen
authors.forename: Kirsi
authors.initials: K
authors.lastname: Autio
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Blennow
authors.forename: Georg
authors.initials: G
authors.lastname: Borgström
authors.forename: Hans
authors.initials: H
authors.lastname: Ehrencrona
authors.forename: Irina
authors.initials: I
authors.lastname: Golovleva
authors.forename: Sverre
authors.initials: S
authors.lastname: Heim
authors.forename: Kristiina
authors.initials: K
authors.lastname: Heinonen
authors.forename: Randi
authors.initials: R
authors.lastname: Hovland
authors.forename: Johann H
authors.initials: JH
authors.lastname: Johannsson
authors.forename: Gitte
authors.initials: G
authors.lastname: Kerndrup
authors.forename: Ann
authors.initials: A
authors.lastname: Nordgren
authors.forename: Lars
authors.initials: L
authors.lastname: Palmqvist
authors.forename: Bertil
authors.initials: B
authors.lastname: Johansson
mesh_terms: D000293:Adolescent; D016009:Chi-Square Distribution; D002648:Child; D002675:Child, Preschool; D002869:Chromosome Aberrations; D015331:Cohort Studies; D020732:Cytogenetic Analysis; D005260:Female; D015329:Gene Rearrangement, T-Lymphocyte; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D015999:Multivariate Analysis; D054218:Precursor T-Cell Lymphoblastic Leukemia-Lymphoma / Q000175:diagnosis / Q000235:genetics*; D011379:Prognosis; D016016:Proportional Hazards Models; D011948:Receptors, Antigen, T-Cell / Q000235:genetics*
chemical_list: D011948:Receptors, Antigen, T-Cell