TY - JOUR
T1 - Intrachromosomal amplification of chromosome 21 is associated with inferior outcomes in children with acute lymphoblastic leukemia treated in contemporary standard-risk children's oncology group studies
T2 - A report from the children's oncology group
AU - Heerema, Nyla A.
AU - Carroll, Andrew J.
AU - Devidas, Meenakshi
AU - Loh, Mignon L.
AU - Borowitz, Michael J.
AU - Gastier-Foster, Julie M.
AU - Larsen, Eric C.
AU - Mattano, Leonard A.
AU - Maloney, Kelly W.
AU - Willman, Cheryl L.
AU - Wood, Brent L.
AU - Winick, Naomi J.
AU - Carroll, William L.
AU - Hunger, Stephen P.
AU - Raetz, Elizabeth A.
N1 - Publisher Copyright:
Copyright © 2017 American Society of Clinical Oncology. All rights reserved.
PY - 2013/9/20
Y1 - 2013/9/20
N2 - Purpose: Five-year overall survival (OS) for children with B-cell precursor acute lymphoblastic leukemia (B-ALL) exceeds 90% with risk-adapted therapy. Age, initial WBC count, genetic aberrations, and minimal residual disease (MRD) are used for risk stratification. Intrachromosomal amplification of a region of chromosome 21 (iAMP21; three or more extra copies of RUNX1 on an abnormal chromosome 21) is a recently identified recurrent genomic lesion associated with inferior outcome in some studies. We investigated the impact of iAMP21 in a large cohort treated in contemporary Children's Oncology Group (COG) ALL trials. Patients and Methods: Fluorescent in situ hybridization for specific genetic aberrations was required at diagnosis. MRD was measured by flow cytometry at end induction. Outcome was measured as event-free survival (EFS) and OS. Results: iAMP21 was found in 158 (2%) of 7,793 patients with B-ALL age ≥ 1 year; 74 (1.5%) of 5,057 standard-risk (SR) patients, and 84 (3.1%) of 2,736 high-risk (HR) patients. iAMP21 was associated with age ≥ 10 years, WBC less than 50,000/μL, female sex, and detectable MRD at day 29. Four-year EFS and OS were significantly worse for patients with iAMP21 and SR B-ALL, but iAMP21 was not a statistically significant prognostic factor in HR patients. There was no interaction between MRD and iAMP21. Among SR patients, day 29 MRD ≥ 0.01% and iAMP21 were associated with the poorest EFS and OS; absence of both was associated with the best outcome. Conclusion: iAMP21 is associated with inferior outcome in pediatric B-ALL, particularly SR patients who require more intensive therapy and are now treated on HR COG ALL protocols.
AB - Purpose: Five-year overall survival (OS) for children with B-cell precursor acute lymphoblastic leukemia (B-ALL) exceeds 90% with risk-adapted therapy. Age, initial WBC count, genetic aberrations, and minimal residual disease (MRD) are used for risk stratification. Intrachromosomal amplification of a region of chromosome 21 (iAMP21; three or more extra copies of RUNX1 on an abnormal chromosome 21) is a recently identified recurrent genomic lesion associated with inferior outcome in some studies. We investigated the impact of iAMP21 in a large cohort treated in contemporary Children's Oncology Group (COG) ALL trials. Patients and Methods: Fluorescent in situ hybridization for specific genetic aberrations was required at diagnosis. MRD was measured by flow cytometry at end induction. Outcome was measured as event-free survival (EFS) and OS. Results: iAMP21 was found in 158 (2%) of 7,793 patients with B-ALL age ≥ 1 year; 74 (1.5%) of 5,057 standard-risk (SR) patients, and 84 (3.1%) of 2,736 high-risk (HR) patients. iAMP21 was associated with age ≥ 10 years, WBC less than 50,000/μL, female sex, and detectable MRD at day 29. Four-year EFS and OS were significantly worse for patients with iAMP21 and SR B-ALL, but iAMP21 was not a statistically significant prognostic factor in HR patients. There was no interaction between MRD and iAMP21. Among SR patients, day 29 MRD ≥ 0.01% and iAMP21 were associated with the poorest EFS and OS; absence of both was associated with the best outcome. Conclusion: iAMP21 is associated with inferior outcome in pediatric B-ALL, particularly SR patients who require more intensive therapy and are now treated on HR COG ALL protocols.
UR - http://www.scopus.com/inward/record.url?scp=84897568967&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84897568967&partnerID=8YFLogxK
U2 - 10.1200/JCO.2013.49.1308
DO - 10.1200/JCO.2013.49.1308
M3 - Article
C2 - 23940221
AN - SCOPUS:84897568967
SN - 0732-183X
VL - 31
SP - 3397
EP - 3402
JO - Journal of Clinical Oncology
JF - Journal of Clinical Oncology
IS - 27
ER -