Justine M Kahn1, Peter D Cole2, Traci M Blonquist3, Kristen Stevenson3, Zhezhen Jin4, Sergio Barrera5, Randy Davila6, Emily Roberts7, Donna S Neuberg3, Uma H Athale8, Luis A Clavell9, Caroline Laverdiere10, Jean-Marie Leclerc10, Bruno Michon11, Marshall A Schorin12, Jennifer J G Welch13, Stephen E Sallan14, Lewis B Silverman14, Kara M Kelly1,15. 1. Division of Pediatric Hematology/Oncology/Stem Cell Transplantation, Columbia University Medical Center, New York, New York. 2. Division of Pediatric Hematology/Oncology, Children's Hospital at Montefiore, Albert Einstein College of Medicine, Bronx, New York. 3. Department of Biostatistics and Computational Biology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts. 4. Department of Biostatistics, Columbia University Medical Center, New York, New York. 5. Department of Economics, University of Minnesota, Minneapolis, Minnesota. 6. Department of Psychology, University of California, Davis, California. 7. Department of Biostatistics, University of Michigan, Ann Arbor, Michigan. 8. Division of Pediatric Hematology/Oncology, McMaster University, Hamilton, Ontario, Canada. 9. Division of Pediatric Oncology, San Jorge Children's Hospital, San Juan, Puerto Rico. 10. Division of Hematology and Oncology, Hospital Sainte-Justine, University of Montreal, Montreal, Canada. 11. Division of Hematology-Oncology, Centre Hospitalier de l'Université Laval, Quebec City, Canada. 12. Inova Fairfax Hospital for Children, Falls Church, Virginia. 13. Division of Pediatric Hematology-Oncology, Hasbro Children's Hospital, Warren Alpert Medical School of Brown University, Providence, Rhode Island. 14. Department of Pediatric Oncology, Dana-Farber Cancer Institute and Division of Pediatric Hematology-Oncology, Boston Children's Hospital, Boston, Massachusetts. 15. Roswell Park Cancer Institute and Women and Children's Hospital, University at Buffalo School of Medicine and Biomedical Sciences, Buffalo, New York.
Abstract
PURPOSE: This study compared the relative incidence of treatment-related toxicities and the event-free and overall survival between Hispanic and non-Hispanic children undergoing therapy for acute lymphoblastic leukemia (ALL) on Dana-Farber Cancer Institute ALL Consortium protocol 05-001. PATIENTS AND METHODS: Secondary analysis of prospectively collected data from a phase III multicenter study in children and adolescents of 1-18 years with previously untreated ALL. RESULTS: Between 2005 and 2011, 794 eligible patients enrolled on DFCI 05-001, 730 of whom were included in this analysis (19% [N = 150] Hispanic, 73% [N = 580] non-Hispanic). Hispanic patients were more likely to be ≥10 years of age (32% vs. 24%, P = 0.045) at diagnosis. Toxicity analyses revealed that Hispanic patients had significantly lower cumulative incidence of bone fracture (P < 0.001) and osteonecrosis (ON; P = 0.047). In multivariable risk regression, the risk of ON was significantly lower in Hispanic patients ≥10 years (HR 0.23; P = 0.006). Hispanic patients had significantly lower 5-year event-free survival (EFS) (79.4%; 95% CI: 71.6-85.2) and overall survival (OS) (89.2%; 95% CI: 82.7-93.4) than non-Hispanic patients (EFS: 87.5%; 95% CI: 84.5-90.0, P = 0.004; OS: 92.7%; 95% CI: 90.2-94.6, P = 0.006). Exploratory analyses revealed differences between Hispanic and non-Hispanic patients in the frequency of common variants in genes related to toxicity or ALL outcome. CONCLUSION: Hispanic children treated for ALL on DFCI 05-001 had fewer bone-related toxicities and inferior survival than non-Hispanic patients. While disease biology is one explanatory variable for outcome disparities, these findings suggest that biologic and non-biologic mechanisms affecting drug delivery and exposure in this population may be important contributing factors as well.
PURPOSE: This study compared the relative incidence of treatment-related toxicities and the event-free and overall survival between Hispanic and non-Hispanic children undergoing therapy for acute lymphoblastic leukemia (ALL) on Dana-Farber Cancer Institute ALL Consortium protocol 05-001. PATIENTS AND METHODS: Secondary analysis of prospectively collected data from a phase III multicenter study in children and adolescents of 1-18 years with previously untreated ALL. RESULTS: Between 2005 and 2011, 794 eligible patients enrolled on DFCI 05-001, 730 of whom were included in this analysis (19% [N = 150] Hispanic, 73% [N = 580] non-Hispanic). Hispanic patients were more likely to be ≥10 years of age (32% vs. 24%, P = 0.045) at diagnosis. Toxicity analyses revealed that Hispanic patients had significantly lower cumulative incidence of bone fracture (P < 0.001) and osteonecrosis (ON; P = 0.047). In multivariable risk regression, the risk of ON was significantly lower in Hispanic patients ≥10 years (HR 0.23; P = 0.006). Hispanic patients had significantly lower 5-year event-free survival (EFS) (79.4%; 95% CI: 71.6-85.2) and overall survival (OS) (89.2%; 95% CI: 82.7-93.4) than non-Hispanic patients (EFS: 87.5%; 95% CI: 84.5-90.0, P = 0.004; OS: 92.7%; 95% CI: 90.2-94.6, P = 0.006). Exploratory analyses revealed differences between Hispanic and non-Hispanic patients in the frequency of common variants in genes related to toxicity or ALL outcome. CONCLUSION: Hispanic children treated for ALL on DFCI 05-001 had fewer bone-related toxicities and inferior survival than non-Hispanic patients. While disease biology is one explanatory variable for outcome disparities, these findings suggest that biologic and non-biologic mechanisms affecting drug delivery and exposure in this population may be important contributing factors as well.
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