Sex-based disparities in outcome in pediatric acute lymphoblastic leukemia: a Children's Oncology Group report.

Abstract

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. Patients 1 to 30.99years 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. 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. 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.