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.

Research output: Contribution to journalArticle

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.

Details

Authors
  • Kristina Karrman
  • Erik Forestier
  • Mats Heyman
  • Mette K Andersen
  • Kirsi Autio
  • Elisabeth Blennow
  • Georg Borgström
  • Hans Ehrencrona
  • Irina Golovleva
  • Sverre Heim
  • Kristiina Heinonen
  • Randi Hovland
  • Johann H Johannsson
  • Gitte Kerndrup
  • Ann Nordgren
  • Lars Palmqvist
  • Bertil Johansson
Organisations
External organisations
  • Uppsala University
Research areas and keywords

Subject classification (UKÄ) – MANDATORY

  • Medical Genetics

Keywords

  • Multivariate Analysis, Male, Kaplan-Meier Estimate, Humans, T-Lymphocyte, Gene Rearrangement, Female, Cytogenetic Analysis, Cohort Studies, Chromosome Aberrations, Preschool, Child, Adolescent, Chi-Square Distribution, Precursor T-Cell Lymphoblastic Leukemia-Lymphoma, Prognosis, Proportional Hazards Models, Receptors, Antigen, T-Cell
Original languageEnglish
Pages (from-to)795-805
JournalGenes, Chromosomes and Cancer
Volume48
Issue number9
Publication statusPublished - 2009
Publication categoryResearch
Peer-reviewedYes

Related research output

Karrman, K., 2014, Division of Clinical Genetics, Lund University. 84 p.

Research output: ThesisDoctoral Thesis (compilation)

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