Site of Care, TDM Still Shape AYA ALL Outcomes: Emily K. Curran, MD

Emily K. Curran, MD, associate professor of internal medicine at the University of Cincinnati College of Medicine, discussed the persistent survival gap between pediatric and adolescent and young adult (AYA) patients with acute lymphoblastic leukemia (ALL), as well as the evolving role of therapeutic drug monitoring (TDM) in managing asparaginase-related toxicity.

Curran co-authored an editorial in Blood Advances commenting on the American Society of Hematology’s 2026 guidelines for frontline management of ALL in AYAs.

How Much of the Survival Gap Comes Down to Site of Care?

Curran described the disparity in outcomes between pediatric and young adult patients with ALL as multifactorial, driven partly by less favorable disease biology in older patients and partly by the psychosocial pressures unique to young adulthood, such as living away from parents for the first time. But she emphasized that where a patient is treated also matters, not necessarily whether that’s a pediatric or adult center, but whether the treating institution has real experience running pediatric-inspired regimens.

Those regimens are demanding: 3 years of treatment with a different protocol at nearly every cycle. Centers with more experience managing that complexity, Curran said, are better equipped to get patients through treatment safely. As she put it, “The important part of treatment of a young adult with ALL is that they receive care at a place that is comfortable with these regimens.”

Is TDM for Asparaginase Available at Adult Centers?

Curran also unpacked the guideline panel’s shift toward recommending prophylactic premedication before asparaginase, a reversal of longstanding practice. Both pediatric and adult providers historically withheld premedication out of concern it would mask hypersensitivity reactions and allow “silent inactivation,” in which patients develop neutralizing antibodies to asparaginase without showing outward symptoms, leaving them on a drug that’s no longer effective.

That calculus changed once TDM became a practical option for identifying silent inactivation. Curran noted that the landmark CALGB 10403 trial (NCT00558519) initially withheld premedication but amended its protocol after encountering significant hypersensitivity, later becoming an early driver of the shift toward routine premedication, with pediatric practice following somewhat later.

On infrastructure, Curran said TDM is typically run as a send-out lab through one of several outside companies rather than performed in-house and that the real barrier has not been logistical difficulty so much as institutions not historically recognizing why identifying silent inactivation mattered. She said she set up the process at her own institution without much difficulty and believes it “should be pretty standard now.”