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Medline ® Abstract for Reference 121

of 'Overview of the treatment of acute lymphoblastic leukemia in children and adolescents'

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.
Heerema NA, Carroll AJ, Devidas M, Loh ML, Borowitz MJ, Gastier-Foster JM, Larsen EC, Mattano LA Jr, Maloney KW, Willman CL, Wood BL, Winick NJ, Carroll WL, Hunger SP, Raetz EA
J Clin Oncol. 2013;31(27):3397. Epub 2013 Aug 12.
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.
Nyla A. Heerema and Julie M. Gastier-Foster, The Ohio State University Wexner Medical Center; Julie M. Gastier-Foster, The Ohio State University College of Medicine and Nationwide Children's Hospital, Columbus, OH; Andrew J. Carroll, University of Alabama at Birmingham, Birmingham, AL; Meenakshi Devidas, University of Florida, Gainesville, FL; Mignon L. Loh, University of California at San Francisco, San Francisco, CA; Michael J. Borowitz, Johns Hopkins Medical Institutions, Baltimore, MD; Eric C. Larsen, Maine Children's Cancer Program, Scarborough, ME; Leonard A. Mattano Jr, Michigan State University College of Human Medicine, Kalamazoo, MI; Kelly W. Maloney and Stephen P. Hunger, Children's Hospital Colorado and University of Colorado School of Medicine, Aurora, CO; Cheryl L. Willman, University of New Mexico, Albuquerque, NM; Brent L. Wood, University of Washington, Seattle, WA; Naomi J. Winick, University of Texas Southwestern Medical Center, Dallas, TX; and William L. Carroll and