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

• Published in: Genes chromosomes & cancer 2009-09, Vol.48 (9), p.795-805
• Main Authors: Karrman, Kristina, Forestier, Erik, Heyman, Mats, Andersen, Mette K., Autio, Kirsi, Blennow, Elisabeth, Borgström, Georg, Ehrencrona, Hans, Golovleva, Irina, Heim, Sverre, Heinonen, Kristiina, Hovland, Randi, Johannsson, Johann H., Kerndrup, Gitte, Nordgren, Ann, Palmqvist, Lars, Johansson, Bertil
• Format: Article
• Language: English
• Subjects: Adolescent; Antigen; Basic Medicine; Chi-Square Distribution; Child; Child, Preschool; Chromosome Aberrations; Cohort Studies; Cytogenetic Analysis; diagnosis; Female; Gene Rearrangement; Gene Rearrangement, T-Lymphocyte; genetics; Hematologi; Hematology; Humans; Kaplan-Meier Estimate; Kaplan-Meiers Estimate; Male; Medical and Health Sciences; Medical Genetics; MEDICIN; Medicin och hälsovetenskap; MEDICINE; Medicinsk genetik; Medicinska och farmaceutiska grundvetenskaper; Multivariate Analysis; Precursor T-Cell Lymphoblastic Leukemia-Lymphoma; Precursor T-Cell Lymphoblastic Leukemia-Lymphoma - diagnosis; Precursor T-Cell Lymphoblastic Leukemia-Lymphoma - genetics; Preschool; Prognosis; Proportional Hazards Models; Receptors; Receptors, Antigen, T-Cell - genetics; T-Cell; T-Lymphocyte
• ISSN: 1045-2257; 1098-2264; 1098-2264
• DOI: 10.1002/gcc.20684

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 × 109/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 ≥200 × 109/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. © 2009 Wiley‐Liss, Inc.