Bridging the gap in pediatric relapsed acute lymphoblastic leukemia treatment : isights and outcomes from the ALL-IC REL 2016 guidelines

Kavčič, Marko (author), Erdélyi, Dániel J. (author), Jazbec, Janez (author)

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.

• Language: English
• Keywords: acute lymphoblastic leukemia intercontinental, ALL-IC, acute lymphoblastic leukemia, relapse, treatment guidelines
• Work type: Article
• Typology: 1.01 - Original Scientific Article
• Organization: MF - Faculty of Medicine
• Publication status: Published
• Publication version: Version of Record
• Year: 2025
• Number of pages: 12 str.
• Numbering: Vol. 72, iss. 12, art. e32063
• PID: 20.500.12556/RUL-176930
• UDC: 616-053.2:616.155.392
• ISSN on article: 1545-5017
• DOI: 10.1002/pbc.32063
• COBISS.SI-ID: 251822083
• Publication date in RUL: 15.12.2025

Record is a part of a journal

• Title: Pediatric blood & cancer
• Shortened title: Ped. blood cancer
• Publisher: Wiley, The International Society of Paediatric Oncology, The American Society of Pediatric Hematology/Oncology
• ISSN: 1545-5017
• COBISS.SI-ID: 490619

Licences

• License: CC BY-NC-ND 4.0, Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International
• Link: http://creativecommons.org/licenses/by-nc-nd/4.0/
• Description: The most restrictive Creative Commons license. This only allows people to download and share the work for no commercial gain and for no other purposes.

Projects

• Funder: OTKA - Ministry of Innovation and Technology of Hungary, National Research, Development and Innovation Fund
• Project number: K-139139