Journal
CANCER
Volume 128, Issue 9, Pages 1863-1870Publisher
WILEY
DOI: 10.1002/cncr.34150
Keywords
acute lymphoblastic leukemia; childhood; disparities; sex; survival
Categories
Funding
- Children's Oncology Group
- National Cancer Institute of the National Institutes of Health [U10CA098543, U10CA098413, U10CA180886, U10CA180899]
- St. Baldrick's Foundation
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Boys with acute lymphoblastic leukemia continue to have lower survival rates compared to girls. This study found that the sex-based disparities still exist in contemporary therapy, with boys experiencing inferior event-free survival and overall survival, primarily due to higher rates of relapse, particularly involving the central nervous system.
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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