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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.

Karrman, Kristina LU ; Forestier, Erik; Heyman, Mats; K Andersen, Mette; Autio, Kirsi; Blennow, Elisabeth; Borgström, Georg; Ehrencrona, Hans LU ; Golovleva, Irina and Heim, Sverre, et al. (2009) In Genes, Chromosomes and Cancer 48(9). p.795-805
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... (More)
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. (Less)
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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
in
Genes, Chromosomes and Cancer
volume
48
issue
9
pages
795 - 805
publisher
John Wiley & Sons
external identifiers
  • wos:000268385700006
  • pmid:19530250
  • scopus:68549109745
ISSN
1045-2257
DOI
10.1002/gcc.20684
language
English
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yes
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3758d914-0fb7-4aae-9d54-4c2702c144da (old id 1434223)
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http://www.ncbi.nlm.nih.gov/pubmed/19530250
date added to LUP
2009-07-03 15:06:00
date last changed
2017-10-22 04:51:48
@article{3758d914-0fb7-4aae-9d54-4c2702c144da,
  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 &gt; or =200 x 10(9)/l (P &lt; 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.},
  author       = {Karrman, Kristina and Forestier, Erik and Heyman, Mats and K Andersen, Mette and Autio, Kirsi and Blennow, Elisabeth and Borgström, Georg and Ehrencrona, Hans and Golovleva, Irina and Heim, Sverre and Heinonen, Kristiina and Hovland, Randi and Johannsson, Johann H and Kerndrup, Gitte and Nordgren, Ann and Palmqvist, Lars and Johansson, Bertil},
  issn         = {1045-2257},
  keyword      = {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},
  language     = {eng},
  number       = {9},
  pages        = {795--805},
  publisher    = {John Wiley & Sons},
  series       = {Genes, Chromosomes and Cancer},
  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.},
  url          = {http://dx.doi.org/10.1002/gcc.20684},
  volume       = {48},
  year         = {2009},
}