Frequency and clinical significance of cytogenetic abnormalities in pediatric T-lineage acute lymphoblastic leukemia: a report from the Children's Cancer Group.
OBJECTIVE
Nonrandom chromosomal translocations are frequently observed in pediatric patients with acute lymphoblastic leukemia (ALL). Specific translocations, such as t(4;11) and t(9;22), identify subgroups of B-lineage ALL patients who have an increased risk of treatment failure. The current study was conducted to determine the prognostic significance of chromosomal translocations in T-lineage ALL patients.


METHODS
The study included 169 children with newly diagnosed T-lineage ALL enrolled between 1988 and 1995 on risk-adjusted protocols of the Children's Cancer Group (CCG) who had centrally reviewed cytogenetics data. Outcome analyses used standard life-table methods.


RESULTS
Presenting features for the current cohort were similar to those of concurrently enrolled patients for whom cytogenetic data were not accepted on central review. The majority of patients (80.5%) were assigned to CCG protocols for high-risk ALL and 86.4% had pseudodiploid (n = 80) or normal diploid (n = 66) karyotypes; modal chromosome number was not a significant prognostic factor. Overall, 103 of 169 (61%) patients had an abnormal karyotype, including 31 with del(6q), 29 with 14q11 breakpoints, 15 with del(9p), 11 with trisomy 8, nine with 11q23 breakpoints, nine with 14q32 translocations, and eight with 7q32-q36 breakpoints. Thirteen patients had the specific 14q11 translocation t(11;14)(p13;q11) and all were classified as poor risk. Patients with any of these translocations had outcomes similar to those with normal diploid karyotypes.


CONCLUSIONS
Chromosomal abnormalities, including specific nonrandom translocations, were frequently observed in a large group of children with T-lineage ALL, but were not significant prognostic factors for this cohort. Thus, contemporary intensive treatment programs result in favorable outcomes for the majority of T-lineage ALL patients, regardless of karyotypic abnormalities, and such features do not identify patients at higher risk for relapse.
Heerema
N A
NA
Department of Medical and Molecular Genetics, Indiana University School of Medicine, Indianapolis 46202-5251, USA. nheerema@medgen.iupui.edu
Sather
H N
HN
Sensel
M G
MG
Kraft
P
P
Nachman
J B
JB
Steinherz
P G
PG
Lange
B J
BJ
Hutchinson
R S
RS
Reaman
G H
GH
Trigg
M E
ME
Arthur
D C
DC
Gaynon
P S
PS
Uckun
F M
FM
D000293:Adolescent; D002648:Child; D002675:Child, Preschool; D002869:Chromosome Aberrations / Q000235:genetics*; D025063:Chromosome Disorders; D015331:Cohort Studies; D003582:Cytogenetics; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D016130:Immunophenotyping; D007223:Infant; D007621:Karyotyping; D015459:Leukemia-Lymphoma, Adult T-Cell / Q000145:classification / Q000235:genetics*; D015993:Life Tables; D008297:Male; D011379:Prognosis; D014178:Translocation, Genetic