Kelly W Maloney1,2, Meenakshi Devidas3, Cindy Wang4, Leonard A Mattano5, Alison M Friedmann6, Patrick Buckley7, Michael J Borowitz8, Andrew J Carroll9, Julie M Gastier-Foster10,11, Nyla A Heerema12, Nina Kadan-Lottick13, Mignon L Loh14,15, Yousif H Matloub16, David T Marshall17, Linda C Stork18, Elizabeth A Raetz19,20, Brent Wood21,22, Stephen P Hunger23,24, William L Carroll19,20, Naomi J Winick25,26. 1. Department of Pediatrics, University of Colorado, Aurora, CO. 2. Children's Hospital Colorado, Aurora, CO. 3. Department of Global Pediatric Medicine, St Jude Children's Research Hospital, Memphis, TN. 4. Department of Biostatistics, Colleges of Medicine, Public Health and Health Professions, University of Florida, Gainesville, FL. 5. HARP Pharma Consulting, Mystic, CT. 6. Department of Pediatrics, Massachusetts General Hospital Cancer Center, Boston, MA. 7. Department of Pathology, Duke University Medical Center, Durham, NC. 8. Department of Pathology, Johns Hopkins University, Baltimore, MD. 9. Department of Genetics, University of Alabama at Birmingham, Birmingham, AL. 10. Department of Pathology and Laboratory Medicine, Nationwide Children's Hospital, Columbus, OH. 11. Department of Pediatrics, Ohio State University College of Medicine, Columbus, OH. 12. Department of Pathology, Wexner Medical Center, Ohio State University, Columbus, OH. 13. Department of Pediatrics, Yale University, New Haven, CT. 14. Department of Pediatrics, Benioff Children's Hospital, San Francisco, CA. 15. Helen Diller Family Comprehensive Cancer, University of California, San Francisco, CA. 16. Department of Pediatrics, Rainbow Babies and Children's Hospital, Cleveland, OH. 17. Department of Radiation Oncology, Medical University of South Carolina, Charleston, SC. 18. Department of Pediatrics, Oregon Health & Science University, Portland, OR. 19. Perlmutter Cancer Center, New York University (NYU) Langone Medical Center, New York, NY. 20. Department of Pediatrics, NYU Langone Medical Center, New York, NY. 21. Department of Pathology, University of Washington, Seattle, WA. 22. Department of Medicine, University of Washington, Seattle, WA. 23. Department of Pediatrics, Children's Hospital of Philadelphia, Philadelphia, PA. 24. Perelman School of Medicine at University of Philadelphia, Philadelphia, PA. 25. Department of Pediatrics, University of Texas (UT) Southwestern, Dallas, TX. 26. Simmons Cancer Center, UT Southwestern, Dallas, TX.
Abstract
PURPOSE:Children'sOncology Group (COG) AALL0331 tested whether intensified postinduction therapy that improves survival in children with high-risk B-cell acute lymphoblastic leukemia (ALL) would also improve outcomes for those with standard-risk (SR) ALL. PATIENTS AND METHODS: AALL0331 enrolled 5,377 patients between 2005 and 2010. All patients received a 3-drug induction with dexamethasone, vincristine, and pegaspargase (PEG) and were then classified as SR low, SR average, or SR high. Patients with SR-average disease were randomly assigned to receive either standard 4-week consolidation (SC) or 8-week intensified augmentedBerlin-Frankfurt-Münster (BFM) consolidation (IC). Those with SR-high disease were nonrandomly assigned to the full COG-augmented BFM regimen, including 2 interim maintenance and delayed intensification phases. RESULTS: The 6-year event-free survival (EFS) rate for all patients enrolled in AALL0331 was 88.96% ± 0.46%, and overall survival (OS) was 95.54% ± 0.31%. For patients with SR-average disease, the 6-year continuous complete remission (CCR) and OS rates for SC versus IC were 87.8% ± 1.3% versus 89.1% ± 1.2% (P = .52) and 95.8% ± 0.8% versus 95.2% ± 0.8% (P = 1.0), respectively. Those with SR-average disease with end-induction minimal residual disease (MRD) of 0.01% to < 0.1% had an inferior outcome compared with those with lower MRD and no improvement with IC (6-year CCR: SC, 77.5% ± 4.8%; IC, 77.1% ± 4.8%; P = .71). At 6 years, the CCR and OS rates among 635 nonrandomly treated patients with SR-high disease were 85.55% ± 1.49% and 92.97% ± 1.08%, respectively. CONCLUSION: The 6-year OS rate for > 5,000 children with SR ALL enrolled in AALL0331 exceeded 95%. The addition of IC to treatment for patients with SR-average disease did not improve CCR or OS, even in patients with higher MRD, in whom it might have been predicted to provide more value. The EFS and OS rates are excellent for this group of patients with SR ALL, with particularly good outcomes for those with SR-high disease.
RCT Entities:
PURPOSE:Children's Oncology Group (COG) AALL0331 tested whether intensified postinduction therapy that improves survival in children with high-risk B-cell acute lymphoblastic leukemia (ALL) would also improve outcomes for those with standard-risk (SR) ALL. PATIENTS AND METHODS: AALL0331 enrolled 5,377 patients between 2005 and 2010. All patients received a 3-drug induction with dexamethasone, vincristine, and pegaspargase (PEG) and were then classified as SR low, SR average, or SR high. Patients with SR-average disease were randomly assigned to receive either standard 4-week consolidation (SC) or 8-week intensified augmented Berlin-Frankfurt-Münster (BFM) consolidation (IC). Those with SR-high disease were nonrandomly assigned to the full COG-augmented BFM regimen, including 2 interim maintenance and delayed intensification phases. RESULTS: The 6-year event-free survival (EFS) rate for all patients enrolled in AALL0331 was 88.96% ± 0.46%, and overall survival (OS) was 95.54% ± 0.31%. For patients with SR-average disease, the 6-year continuous complete remission (CCR) and OS rates for SC versus IC were 87.8% ± 1.3% versus 89.1% ± 1.2% (P = .52) and 95.8% ± 0.8% versus 95.2% ± 0.8% (P = 1.0), respectively. Those with SR-average disease with end-induction minimal residual disease (MRD) of 0.01% to < 0.1% had an inferior outcome compared with those with lower MRD and no improvement with IC (6-year CCR: SC, 77.5% ± 4.8%; IC, 77.1% ± 4.8%; P = .71). At 6 years, the CCR and OS rates among 635 nonrandomly treated patients with SR-high disease were 85.55% ± 1.49% and 92.97% ± 1.08%, respectively. CONCLUSION: The 6-year OS rate for > 5,000 children with SR ALL enrolled in AALL0331 exceeded 95%. The addition of IC to treatment for patients with SR-average disease did not improve CCR or OS, even in patients with higher MRD, in whom it might have been predicted to provide more value. The EFS and OS rates are excellent for this group of patients with SR ALL, with particularly good outcomes for those with SR-high disease.
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