Male Sex Had an Adverse Impact on Outcomes of Pediatric B-Lineage Acute Lymphoblastic Leukemia

Purpose

Despite the improved overall survival of childhood B-lineage acute lymphoblastic leukemia (B-ALL) under contemporary risk-directed therapy, ~15% patients still experience relapse which calls for additional prognosis predicting factors. We aim to investigate the impact of sex on clinical outcomes in childhood B-ALL.

Patients and Methods

Between January 2, 2015, and December 31, 2019, 6916 pediatric patients with newly diagnosed B-ALL were enrolled in the Chinese Children's Cancer Group ALL-2015 clinical trial (CCCG-ALL-2015, ChiCTR-IPR-14005706).

Results

Among the 6916 cases pediatric B-ALL, the ratio of males to females was 1:0.74 (males 3982, 57.6%; females 2934, 42.4%). An inferior 5-year EFS was observed in males compared with females (79.7%; 95%CI, 78.5-81.0 vs 83.5%; 95%CI, 82.1-84.9; P< .001). Male sex was identified as an independent poor EFS predictor by a multivariant cox model (HR, 1.19; 95%CI, 1.05-1.35; P= .006). Incidence of relapse was the major difference between the two groups. Males had increased relapse risk compared with females, with a 16.4% (95%CI: 15.2-17.6) 5-year cumulative incidence of relapse (females: 12.2%; 95%CI, 11.0-13.4; P< .001) and a 2.9% (95%CI: 2.4-3.5) 5-year cumulative incidence of central nervous system leukemia relapse (females: 1.6%; 95%CI, 1.2-2.2; P< .001). Although the sex impacted the EFS and CIR, males and females achieved a comparable 5-year OS (93.2%; 95%CI, 92.3-94.2 vs 93.2%; 95%CI, 92.4-94.0; P= .800), indicative of the successful salvage therapy for males. Compared with females, males more often had BCR::ABL1 fusion (5.83%, 232/3982 vs 3.31%, 97/2934; P< .001), but no sex-associated difference in the incidence of ETV6::RUNX1, KMT2A-rearranged or TCF3::PBX1 subtypes were noted. Males with BCR::ABL1 fusion or ETV6::RUNX1 fusion exhibited higher relapse rates than females in the same subtype (BCR::ABL1: 38.4%, 89/232 vs 26.8%, 26/97; P= .045; ETV6::RUNX1: 11.9%, 100/838 vs 4.9%, 30/615; P< .001). Such difference was not seen in KMT2A-rearranged or TCF3::PBX1 subtypes. BCR::ABL1 was identified as a male-specific relapse predictor using the multivariate competing risks model.

Conclusions

Sex impacts the prognosis of childhood B-ALL. Males has an inferior EFS and is identified as a relapse predictor in B-ALL which warrants the development of male-adapted regimen to prevent disease reoccurrence. The mechanism underlying the sex impact needs further investigation.

No relevant conflicts of interest to declare.