Abstract
Relapse remains the main obstacle to curing childhood acute lymphoblastic leukemia (ALL). The aims of this study were to compare incidence of relapse, prognostic factors, and survival after relapse between three consecutive Nordic Society of Pediatric Hematology and Oncology trials. Relapse occurred as a primary event in 638 of 4 458 children (1.0–14.9 years) diagnosed with Ph-negative ALL between 1992 and 2018. The 5-year cumulative incidence of relapse was 17.3% (95% CI 15.4–19.2%) and 16.5% (95% CI 14.3–18.8%) for patients in the ALL1992 and ALL2000 trials, respectively, but decreased to 8.4% (95% CI 7.0–10.1%) for patients in the ALL2008 trial. No changes in duration of first complete remission and site of relapse were observed over time; however, high hyperdiploidy, and t(12;21) decreased in the ALL2008 trial. The 4-year overall survival after relapse was 56.6% (95% CI 52.5–60.5%) and no statistically significant temporal improvements were observed. Age ≥10 years, T-cell immunophenotype, bone-marrow involvement, early and very early relapse, hypodiploidy, and Down syndrome all independently predicted worse outcome after relapse. Improvements in the primary treatment of childhood ALL has resulted in fewer relapses. However, failure to improve outcome of remaining relapses suggests a selection of harder-to-cure relapses and calls for new therapeutic strategies.
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Acknowledgements
This work was supported by grants from the Danish Cancer Society, the A.P. Møller Foundation, and Tømrermester Jørgen Holm & Hustru Elisa F. Hansens Foundation. The funders had no role in the design or conduct of the study.
We thank all clinicians assisting with the data collection and the Nordic Society of Paediatric Haematology and Oncology (NOPHO).
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KSJ designed the study, analyzed and interpreted data and wrote the manuscript; TO designed the study, interpreted data and edited the manuscript; PML designed the study, interpreted data and edited the manuscript; TF designed the study, interpreted data and edited the manuscript; OGJ designed the study, interpreted data and edited the manuscript; PS designed the study, interpreted data and edited the manuscript; KS designed the study, interpreted data and edited the manuscript; MH designed the study, interpreted data and edited the manuscript; UNN designed the study, reviewed cytogenetics, interpreted data and edited the manuscript; BA designed the study, interpreted data and edited the manuscript; HS designed the study, interpreted data and edited the manuscript. All authors approved the final manuscript.
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BA declares the following: sponsor for the investigator-initiated NOR-GRASPALL 2016 study; speaker and/or advisory board honoraria from Erytech (2020) and Servier (2021). Kjeld Schmiegelow declares the following: speaker and/or advisory board honoraria from Jazz Pharmaceuticals (2020) and Servier (2020); speaker’s fee from Amgen (2020) and Medscape (2020); educational grant from Servier (2020). The remaining authors have no competing interests to declare.
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Jensen, K.S., Oskarsson, T., Lähteenmäki, P.M. et al. Temporal changes in incidence of relapse and outcome after relapse of childhood acute lymphoblastic leukemia over three decades; a Nordic population-based cohort study. Leukemia 36, 1274–1282 (2022). https://doi.org/10.1038/s41375-022-01540-1
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DOI: https://doi.org/10.1038/s41375-022-01540-1