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: A report from the children's oncology group

Nyla A. Heerema, Andrew J. Carroll, Meenakshi Devidas, Mignon L. Loh, Michael J. Borowitz, Julie M. Gastier-Foster, Eric C. Larsen, Leonard A. Mattano, Kelly W. Maloney, Cheryl L. Willman, Brent L. Wood, Naomi J. Winick, William L. Carroll, Stephen P. Hunger, Elizabeth A. Raetz

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74 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)3397-3402
Number of pages6
JournalJournal of Clinical Oncology
Volume31
Issue number27
DOIs
StatePublished - Sep 20 2013

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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    Heerema, N. A., Carroll, A. J., Devidas, M., Loh, M. L., Borowitz, M. J., Gastier-Foster, J. M., Larsen, E. C., Mattano, L. A., Maloney, K. W., Willman, C. L., Wood, B. L., Winick, N. J., Carroll, W. L., Hunger, S. P., & Raetz, E. A. (2013). 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: A report from the children's oncology group. Journal of Clinical Oncology, 31(27), 3397-3402. https://doi.org/10.1200/JCO.2013.49.1308