Temporal changes in incidence of relapse and outcome after relapse of childhood acute lymphoblastic leukemia over three decades; a Nordic population-based cohort study

• Published in: Leukemia Vol. 36; no. 5; pp. 1274 - 1282
• Main Authors: Jensen, Karen Schow, Oskarsson, Trausti, Lähteenmäki, Päivi M., Flaegstad, Trond, Jónsson, Ólafur Gísli, Svenberg, Petter, Schmiegelow, Kjeld, Heyman, Mats, Norén-Nyström, Ulrika, Schrøder, Henrik, Albertsen, Birgitte Klug
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 01-05-2022; Nature Publishing Group
• Subjects: 692/308/174; 692/699/1541/1990/283/2125; Acute lymphoblastic leukemia; Bone marrow; Cancer Research; Child; Children; Clinical trials; Cohort analysis; Cohort Studies; Critical Care Medicine; Down's syndrome; Hematology; Humans; Hypodiploidy; Incidence; Infant; Intensive; Internal Medicine; Leukemia; Lymphatic leukemia; Lymphocytes T; Medical prognosis; Medicin och hälsovetenskap; Medicine; Medicine & Public Health; Oncology; onkologi; Patients; Pediatrics; pediatrik; Population studies; Population-based studies; Precursor Cell Lymphoblastic Leukemia-Lymphoma - drug therapy; Precursor Cell Lymphoblastic Leukemia-Lymphoma - epidemiology; Precursor Cell Lymphoblastic Leukemia-Lymphoma - genetics; Recurrence; Remission; Remission Induction; Statistical analysis; Survival; Treatment Outcome
• ISSN: 0887-6924; 1476-5551; 1476-5551
• DOI: 10.1038/s41375-022-01540-1

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.