Adherence-enhancing intervention and relapse in childhood acute lymphoblastic leukemia: results from the Children’s Oncology Group randomized trial ACCL1033

Bhatia S, Hageman L, Chen Y, Wadhwa A, Wong FL, McQuaid EL, Freyer DR, Mba N, Aristizabal P, Raetz E, Landier W. Adherence-enhancing intervention and relapse in childhood acute lymphoblastic leukemia: results from the Children’s Oncology Group randomized trial ACCL1033. Leukemia. 2026 May;40(5):1062-1066. doi: 10.1038/s41375-026-02951-0. Epub 2026 Apr 13. PMID: 41975001; PMCID: PMC13149298.

Durable remissions in children with acute lymphoblastic leukemia (ALL) require an 18-to-24-month-long maintenance phase with daily self-administered oral mercaptopurine (6MP) [1–4]. In a previous multicenter study, we showed that 6MP adherence rates <95% were associated with a 2.7-fold higher relapse risk [4]. Over 40% of relapses in children entering maintenance in first remission were attributable to suboptimal 6MP adherence [4–6]. The most common reason for missing 6MP was forgetfulness [5]; adherent patients endorsed parental vigilance to overcome forgetfulness [7]. These findings prompted a multicenter phase III randomized clinical trial (RCT) to test the efficacy of adherence-enhancing strategies in children and adolescents with ALL receiving 6MP during maintenance [8]. Parents of children with ALL who were <12 years old (yo) at enrollment, and parents and adolescents with ALL who were ≥12yo were randomized to receive education alone (EDU) or an intervention package (IP) that addressed facilitators/barriers to adherence (i.e., forgetfulness, parental vigilance) [5, 7]. The primary aim of the trial was to determine the impact of EDU vs. IP on 6MP adherence; the results of this trial varied by patient age [8]. While post-intervention 6MP adherence rates were comparably high for EDU vs. IP in the <12yo participants (p = 0.53), they were significantly higher for IP (p = 0.04) among the ≥12yo [8]. In this report we describe results of the exploratory aim that examined relapse risk by intervention arm. We tested the hypothesis that EDU will result in higher relapse risk vs. IP among the ≥12yo participants but will have comparable relapse risks among <12yo participants.