Leonard A Mattano1, Meenakshi Devidas2, Kelly W Maloney3, Cindy Wang4, Alison M Friedmann5, Patrick Buckley6, Michael J Borowitz7, Andrew J Carroll8, Julie M Gastier-Foster9,10, Nyla A Heerema11, Nina S Kadan-Lottick12, Yousif H Matloub13, David T Marshall14, Linda C Stork15, Mignon L Loh16, Elizabeth A Raetz17, Brent L Wood18, Stephen P Hunger19, William L Carroll17, Naomi J Winick20. 1. HARP Pharma Consulting, Mystic, CT. 2. Department of Global Pediatric Medicine, St Jude Children's Research Hospital, Memphis, TN. 3. Department of Pediatrics, University of Colorado and Children's Hospital Colorado, Aurora, CO. 4. Department of Biostatistics, Colleges of Medicine, Public Health, and Health Professions, University of Florida, Gainesville, FL. 5. Department of Pediatrics, Massachusetts General Hospital Cancer Center, Boston, MA. 6. Department of Pathology, Duke University Medical Center, Durham, NC. 7. Department of Pathology, Johns Hopkins University, Baltimore, MD. 8. Department of Genetics, Children's Hospital of Alabama, Birmingham, AL. 9. Department of Pathology and Laboratory Medicine, Nationwide Children's Hospital, Ohio State University College of Medicine, Columbus, OH. 10. Departments of Pathology and Pediatrics, Ohio State University College of Medicine, Columbus, OH. 11. Department of Pathology, Wexner Medical Center, Ohio State University, Columbus, OH. 12. Department of Pediatrics, Yale University and Yale Cancer Center, New Haven, CT. 13. Case Western Reserve University School of Medicine, Cleveland, OH. 14. Department of Radiation Oncology, Medical University of South Carolina, Charleston, SC. 15. Department of Pediatrics, Oregon Health and Science University, Portland, OR. 16. Department of Pediatrics, Benioff Children's Hospital and the Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, San Francisco, CA. 17. Perlmutter Cancer Center and Department of Pediatrics, NYU Langone Medical Center, New York, NY. 18. Departments of Pathology and Medicine, University of Washington, Seattle, WA. 19. Department of Pediatrics and The Center for Childhood Cancer Research, Children's Hospital of Philadelphia and the Perelman School of Medicine at The University of Philadelphia, Philadelphia, PA. 20. Department of Pediatrics, UT Southwestern, Simmons Cancer Center, Dallas, TX.
Abstract
PURPOSE: Children's Oncology Group (COG) AALL0331 tested whether pegaspargase intensification on a low-intensity chemotherapy backbone would improve the continuous complete remission (CCR) rate in a low-risk subset of children with standard-risk B-acute lymphoblastic leukemia (ALL). METHODS: AALL0331 enrolled 5,377 patients with National Cancer Institute standard-risk B-ALL (age 1-9 years, WBC < 50,000/μL) between 2005 and 2010. Following a common three-drug induction, a cohort of 1,857 eligible patients participated in the low-risk ALL random assignment. Low-risk criteria included no extramedullary disease, < 5% marrow blasts by day 15, end-induction marrow minimal residual disease < 0.1%, and favorable cytogenetics (ETV6-RUNX1 fusion or simultaneous trisomies of chromosomes 4, 10, and 17). Random assignment was to standard COG low-intensity therapy (including two pegaspargase doses, one each during induction and delayed intensification) with or without four additional pegaspargase doses at 3-week intervals during consolidation and interim maintenance. The study was powered to detect a 4% improvement in 6-year CCR rate from 92% to 96%. RESULTS: The 6-year CCR and overall survival (OS) rates for the entire low-risk cohort were 94.7% ± 0.6% and 98.7% ± 0.3%, respectively. The CCR rates were similar between arms (intensified pegaspargase 95.3% ± 0.8% v standard 94.0% ± 0.8%; P = .13) with no difference in OS (98.1% ± 0.5% v 99.2% ± 0.3%; P = .99). Compared to a subset of standard-risk study patients given identical therapy who had the same early response characteristics but did not have favorable or unfavorable cytogenetics, outcomes were significantly superior for low-risk patients (CCR hazard ratio 1.95; P = .0004; OS hazard ratio 5.42; P < .0001). CONCLUSION: Standard COG therapy without intensified pegaspargase, which can easily be given as an outpatient with limited toxicity, cures nearly all children with B-ALL identified as low-risk by clinical, early response, and favorable cytogenetic criteria.
PURPOSE: Children's Oncology Group (COG) AALL0331 tested whether pegaspargase intensification on a low-intensity chemotherapy backbone would improve the continuous complete remission (CCR) rate in a low-risk subset of children with standard-risk B-acute lymphoblastic leukemia (ALL). METHODS: AALL0331 enrolled 5,377 patients with National Cancer Institute standard-risk B-ALL (age 1-9 years, WBC < 50,000/μL) between 2005 and 2010. Following a common three-drug induction, a cohort of 1,857 eligible patients participated in the low-risk ALL random assignment. Low-risk criteria included no extramedullary disease, < 5% marrow blasts by day 15, end-induction marrow minimal residual disease < 0.1%, and favorable cytogenetics (ETV6-RUNX1 fusion or simultaneous trisomies of chromosomes 4, 10, and 17). Random assignment was to standard COG low-intensity therapy (including two pegaspargase doses, one each during induction and delayed intensification) with or without four additional pegaspargase doses at 3-week intervals during consolidation and interim maintenance. The study was powered to detect a 4% improvement in 6-year CCR rate from 92% to 96%. RESULTS: The 6-year CCR and overall survival (OS) rates for the entire low-risk cohort were 94.7% ± 0.6% and 98.7% ± 0.3%, respectively. The CCR rates were similar between arms (intensified pegaspargase 95.3% ± 0.8% v standard 94.0% ± 0.8%; P = .13) with no difference in OS (98.1% ± 0.5% v 99.2% ± 0.3%; P = .99). Compared to a subset of standard-risk study patients given identical therapy who had the same early response characteristics but did not have favorable or unfavorable cytogenetics, outcomes were significantly superior for low-risk patients (CCR hazard ratio 1.95; P = .0004; OS hazard ratio 5.42; P < .0001). CONCLUSION: Standard COG therapy without intensified pegaspargase, which can easily be given as an outpatient with limited toxicity, cures nearly all children with B-ALL identified as low-risk by clinical, early response, and favorable cytogenetic criteria.
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Authors: Kelly W Maloney; Meenakshi Devidas; Cindy Wang; Leonard A Mattano; Alison M Friedmann; Patrick Buckley; Michael J Borowitz; Andrew J Carroll; Julie M Gastier-Foster; Nyla A Heerema; Nina Kadan-Lottick; Mignon L Loh; Yousif H Matloub; David T Marshall; Linda C Stork; Elizabeth A Raetz; Brent Wood; Stephen P Hunger; William L Carroll; Naomi J Winick Journal: J Clin Oncol Date: 2019-12-11 Impact factor: 44.544
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Authors: Sumit Gupta; David T Teachey; Zhiguo Chen; Karen R Rabin; Kimberly P Dunsmore; Eric C Larsen; Kelly W Maloney; Leonard A Mattano; Stuart S Winter; Andrew J Carroll; Nyla A Heerema; Michael J Borowitz; Brent L Wood; William L Carroll; Elizabeth A Raetz; Naomi J Winick; Mignon L Loh; Stephen P Hunger; Meenakshi Devidas Journal: Cancer Date: 2022-02-24 Impact factor: 6.860