Sumit Gupta1, David T Teachey2, Zhiguo Chen3, Karen R Rabin4, Kimberly P Dunsmore5, Eric C Larsen6, Kelly W Maloney7, Leonard A Mattano8, Stuart S Winter9, Andrew J Carroll10, Nyla A Heerema11, Michael J Borowitz12, Brent L Wood13, William L Carroll14, Elizabeth A Raetz14, Naomi J Winick15, Mignon L Loh16, Stephen P Hunger2, Meenakshi Devidas17. 1. Division of Haematology/Oncology, The Hospital for Sick Children, Toronto, Canada. 2. Department of Pediatrics and Center for Childhood Cancer Research, Children's Hospital of Philadelphia and Perelman School of Medicine, University of Philadelphia, Philadelphia, Pennsylvania. 3. Department of Biostatistics, Colleges of Medicine, Public Health, and Health Professions, University of Florida, Gainesville, Florida. 4. Department of Pediatrics, Baylor College of Medicine, Houston, Texas. 5. Department of Pediatrics, University of Virginia School of Medicine, Charlottesville, Virginia. 6. Department of Pediatrics, Maine Children's Cancer Program, Scarborough, Maine. 7. Department of Pediatrics, University of Colorado and Children's Hospital Colorado, Aurora, Colorado. 8. HARP Pharma Consulting, Mystic, Connecticutt. 9. Children's Hospitals and Clinics of Minnesota, Minneapolis, Minnesota. 10. Department of Genetics, University of Alabama at Birmingham, Birmingham, Alabama. 11. Department of Pathology, The Ohio State University Wexner School of Medicine, Columbus, Ohio. 12. Division of Hematologic Pathology, Johns Hopkins University, Baltimore, Maryland. 13. Department of Laboratory Medicine, Children's Hospital Los Angeles, Los Angeles, California. 14. Department of Pediatrics, NYU Langone Health, New York, New York. 15. Department of Pediatrics, Harold C. Simmons Comprehensive Cancer Center, UT Southwestern Medical Center, Dallas, Texas. 16. Division of Pediatric Hematology, Oncology, Bone Marrow Transplant and Cellular Therapy, Seattle Children's Hospital, Seattle, Washington. 17. Department of Global Pediatric Medicine, St. Jude Children's Research Hospital, Memphis, Tennessee.
Abstract
BACKGROUND: Boys with acute lymphoblastic leukemia (ALL) have historically experienced inferior survival compared to girls. This study determined whether sex-based disparities persist with contemporary therapy and whether patterns of treatment failure vary by sex. METHODS: Patients 1 to 30.99 years old were enrolled on frontline Children's Oncology Group trials between 2004 and 2014. Boys received an additional year of maintenance therapy. Sex-based differences in the distribution of various prognosticators, event-free survival (EFS) and overall survival (OS), and subcategories of relapse by site were explored. RESULTS: A total of 8202 (54.4% male) B-cell ALL (B-ALL) and 1562 (74.3% male) T-cell ALL (T-ALL) patients were included. There was no sex-based difference in central nervous system (CNS) status. Boys experienced inferior 5-year EFS and OS (EFS, 84.6% ± 0.5% vs 86.0% ± 0.6%, P = .009; OS, 91.3% ± 0.4% vs 92.5% ± 0.4%, P = .02). This was attributable to boys with B-ALL, who experienced inferior EFS (hazard ratio [HR], 1.2; 95% confidence interval [95% CI], 1.1-1.3; P = .004) and OS (HR, 1.2; 95% CI, 1.0-1.4; P = .046) after adjustment for prognosticators. Inferior B-ALL outcomes in boys were attributable to more relapses (5-year cumulative incidence 11.2% ± 0.5% vs 9.6% ± 0.5%; P = .001), particularly involving the CNS (4.2% ± 0.3% vs 2.5% ± 0.3%; P < .0001). There was no difference in isolated bone marrow relapses (5.4% ± 0.4% vs 6.2% ± 0.4%; P = .49). There were no sex-based differences in EFS or OS in T-ALL. CONCLUSIONS: Sex-based disparities in ALL persist, attributable to increased CNS relapses in boys with B-ALL. Studies of potential mechanisms are warranted. Improved strategies to identify and modify treatment for patients at highest risk of CNS relapse may have particular benefit for boys.
BACKGROUND: Boys with acute lymphoblastic leukemia (ALL) have historically experienced inferior survival compared to girls. This study determined whether sex-based disparities persist with contemporary therapy and whether patterns of treatment failure vary by sex. METHODS: Patients 1 to 30.99 years old were enrolled on frontline Children's Oncology Group trials between 2004 and 2014. Boys received an additional year of maintenance therapy. Sex-based differences in the distribution of various prognosticators, event-free survival (EFS) and overall survival (OS), and subcategories of relapse by site were explored. RESULTS: A total of 8202 (54.4% male) B-cell ALL (B-ALL) and 1562 (74.3% male) T-cell ALL (T-ALL) patients were included. There was no sex-based difference in central nervous system (CNS) status. Boys experienced inferior 5-year EFS and OS (EFS, 84.6% ± 0.5% vs 86.0% ± 0.6%, P = .009; OS, 91.3% ± 0.4% vs 92.5% ± 0.4%, P = .02). This was attributable to boys with B-ALL, who experienced inferior EFS (hazard ratio [HR], 1.2; 95% confidence interval [95% CI], 1.1-1.3; P = .004) and OS (HR, 1.2; 95% CI, 1.0-1.4; P = .046) after adjustment for prognosticators. Inferior B-ALL outcomes in boys were attributable to more relapses (5-year cumulative incidence 11.2% ± 0.5% vs 9.6% ± 0.5%; P = .001), particularly involving the CNS (4.2% ± 0.3% vs 2.5% ± 0.3%; P < .0001). There was no difference in isolated bone marrow relapses (5.4% ± 0.4% vs 6.2% ± 0.4%; P = .49). There were no sex-based differences in EFS or OS in T-ALL. CONCLUSIONS: Sex-based disparities in ALL persist, attributable to increased CNS relapses in boys with B-ALL. Studies of potential mechanisms are warranted. Improved strategies to identify and modify treatment for patients at highest risk of CNS relapse may have particular benefit for boys.
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