Nyla A Heerema1, 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. 1. 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 Elizabeth A. Raetz, The New York University Cancer Institute, New York University Langone Medical Center, New York, NY.
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.
RCT Entities:
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.
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