Possible explanations
Dr. Gupta noted that the inferior outcomes among boys may be attributable to extramedullary relapses among patients with B-ALL.
In addition, the lack of sex-based differences in T-ALL may be caused in part by the increased use of CNS radiation in this population. Previous studies in which CNS radiation was omitted showed an increase in CNS relapsed rates among boys but not girls, he pointed out.
“This does imply that in the more recent generation of T-lineage ALL treatment trials that we’ll need to monitor sex-based differences in outcome, as fewer and fewer patients with T-ALL disease received cranial radiation in these more recent trials and in contemporary therapy,” he said.
One possible mechanism for sex-based outcome differences might be differences in steroid metabolism, as suggested by the higher osteonecrosis rate among girls, he added.
In the question-and-answer following the presentation, William G. Woods, MD, from Emory University, Atlanta, asked what role testicular relapse played in outcomes.
Dr. Gupta replied that the investigators had considered that the excess risk for extramedullary relapse in boys might be accounted for by testicular relapse, but “when you take away testicular relapse from those numbers and really just concentrate on CNS, it’s still that substantial difference when you’re talking about B-lineage disease.”
In patients with T-ALL as well, CNS relapse was more common in boys after controlling for testicular relapse, he said.
Another audience member asked whether the data suggest a benefit to treating boys with CNS-penetrating drugs such as dexamethasone or high-dose methotrexate,
Dr. Gupta said that it’s still uncertain whether it is clinically sound to subject a boy with otherwise–standard-risk disease to more intensive high-risk therapy, given the relatively small absolute differences in outcomes between the sexes.
The study was supported by grants from the National Cancer Institute and the St. Baldrick’s Foundation. Dr. Gupta, Dr. Woods, and Dr. Meret had no relevant conflicts of interest to report.