TY - JOUR
T1 - Down syndrome childhood acute lymphoblastic leukemia has a unique spectrum of sentinel cytogenetic lesions that influences treatment outcome
T2 - A report from the Children's Oncology Group
AU - Maloney, Kelly W.
AU - Carroll, William L.
AU - Carroll, Andrew J.
AU - Devidas, Meenakshi
AU - Borowitz, Michael J.
AU - Martin, Paul L.
AU - Pullen, Jeanette
AU - Whitlock, James A.
AU - Willman, Cheryl L.
AU - Winick, Naomi J.
AU - Camitta, Bruce M.
AU - Hunger, Stephen P.
PY - 2010/8/19
Y1 - 2010/8/19
N2 - Children with Down syndrome (DS) have an increased risk of acute lymphoblastic leukemia (ALL) and an inferior outcome. We reviewed data from 2811 children with ALL enrolled in Children's Oncology Group P9900, which included prospective testing for the major cytogenetic lesions in childhood ALL: ETV6-RUNX1, TCF3-PBX1, BCR-ABL1, and MLL translocations and trisomies of chromosomes 4 and 10. Eighty (3%) B-precursor ALL patients had DS. Age, sex, white blood cell count, and risk group were similar between DS-ALL and non-DS-ALL but significantly more patients with DS-ALL were white (91.2% vs 76.4%, P = .001). Children with DS-ALL had lower rates of the favorable cytogenetic lesions ETV6-RUNX1 (2.5% vs 24%, P < .001) and trisomies 4 and 10 (7.7% vs 24%, P < .001). Five-year event-free (EFS) and overall survival (OS) were inferior in children with DS-ALL: 69.9% ± 8.6% versus 78.1% ± 1.2% (P = .078), and 85.8% ± 6.5% versus 90.0% ± 0.9% (P = .033). However, when children with MLL translocations, BCR-ABL1, ETV6-RUNX1, and trisomies 4 and 10 were excluded, the EFS and OS were similar for children with and without DS (EFS 68.0 % ± 9.3% vs 70.5% ± 1.9%, P = .817; and OS 86.7% ± 6.7% vs 85.4% ± 1.5%; P = .852), both overall and adjusted for race. DS-ALL displays a unique spectrum of biologic subtypes with different frequencies of sentinel cytogenetic lesions having a large influence on outcome.
AB - Children with Down syndrome (DS) have an increased risk of acute lymphoblastic leukemia (ALL) and an inferior outcome. We reviewed data from 2811 children with ALL enrolled in Children's Oncology Group P9900, which included prospective testing for the major cytogenetic lesions in childhood ALL: ETV6-RUNX1, TCF3-PBX1, BCR-ABL1, and MLL translocations and trisomies of chromosomes 4 and 10. Eighty (3%) B-precursor ALL patients had DS. Age, sex, white blood cell count, and risk group were similar between DS-ALL and non-DS-ALL but significantly more patients with DS-ALL were white (91.2% vs 76.4%, P = .001). Children with DS-ALL had lower rates of the favorable cytogenetic lesions ETV6-RUNX1 (2.5% vs 24%, P < .001) and trisomies 4 and 10 (7.7% vs 24%, P < .001). Five-year event-free (EFS) and overall survival (OS) were inferior in children with DS-ALL: 69.9% ± 8.6% versus 78.1% ± 1.2% (P = .078), and 85.8% ± 6.5% versus 90.0% ± 0.9% (P = .033). However, when children with MLL translocations, BCR-ABL1, ETV6-RUNX1, and trisomies 4 and 10 were excluded, the EFS and OS were similar for children with and without DS (EFS 68.0 % ± 9.3% vs 70.5% ± 1.9%, P = .817; and OS 86.7% ± 6.7% vs 85.4% ± 1.5%; P = .852), both overall and adjusted for race. DS-ALL displays a unique spectrum of biologic subtypes with different frequencies of sentinel cytogenetic lesions having a large influence on outcome.
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U2 - 10.1182/blood-2009-07-235291
DO - 10.1182/blood-2009-07-235291
M3 - Article
C2 - 20442364
AN - SCOPUS:77954491626
SN - 0006-4971
VL - 116
SP - 1045
EP - 1050
JO - Blood
JF - Blood
IS - 7
ER -