Bridging the Gap in Pediatric Relapsed Acute Lymphoblastic Leukemia Treatment: Insights and Outcomes From the ALL-IC REL 2016 Guidelines.

Background: The Acute Lymphoblastic Leukemia InterContinental (ALL-IC) Study Group exemplifies the potential of broad international collaboration. Patient outcomes have improved by standardizing therapeutic options and employing flow cytometry-based minimal residual disease (MRD) for treatment stratification. Nevertheless, relapse occurs in 10%-20% of cases, with survival rates falling short of benchmarks set by top-tier published studies.

Objectives: We aimed to unify treatment guidelines for children with first relapse of ALL across the ALL-IC network, analyze post-relapse outcomes, and report findings from an observational registry.

Methods: Patients were stratified as standard-risk (SR) or high-risk (HR) based on relapse features and genetics. HR criteria included T-cell immunophenotype, very early or early isolated bone marrow relapse, and relapse post-stem cell transplant (SCT). SR was assigned to all others. SCT was indicated in the whole HR group and in SR patients with poor responses (MRD ≥ 0.1% on Day 29).

Results: Among 370 patients (mean age 9 years; 33.2% female) diagnosed with first relapse between 2017 and 2021, 90.5% had received ALL-IC-Berlin-Frankfurt-Münster (BFM) 2009 treatment initially. Upon relapse, 46.8% were classified as SR and 53.2% as HR. Complete remission rates post-induction were 84% (SR) and 56% (HR). MRD < 0.1% was achieved by 53% (SR) and 29% (HR). Five-year overall survival was 50.5% (74% SR, 32% HR). HR outcomes were hindered by disease progression, treatment toxicity, and posttransplant complications.

Conclusions: This inaugural ALL-IC REL Consortium report demonstrates promising SR outcomes, akin to the International Study for the Treatment of Childhood Relapsed ALL (IntReALL) findings, but highlights poor HR outcomes with standard chemotherapy. Novel therapeutic strategies are urgently needed in upcoming ALL-IC-BFM REL protocols.