Department of Clinical Medicine

TY - JOUR

T1 - Temporal changes in incidence of relapse and outcome after relapse of childhood acute lymphoblastic leukemia over three decades; a Nordic population-based cohort study

AU - Jensen, Karen Schow

AU - Oskarsson, Trausti

AU - Lähteenmäki, Päivi Maria

AU - Flaegstad, Trond

AU - Jónsson, Ólafur

AU - Svenberg, Petter

AU - Schmiegelow, Kjeld

AU - Heyman, Mats

AU - Norén-Nyström, Ulrika

AU - Schrøder, Henrik

AU - Albertsen, BK

PY - 2022/5

Y1 - 2022/5

N2 - 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.

AB - 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.

KW - 1ST RELAPSE

KW - BLINATUMOMAB

KW - CHEMOTHERAPY

KW - CHILDREN

KW - CLINICAL-SIGNIFICANCE

KW - FREE SURVIVAL

KW - MINIMAL RESIDUAL DISEASE

KW - PROGNOSTIC-FACTORS

KW - RECEPTOR T-CELLS

KW - YOUNG-ADULTS

KW - Recurrence

KW - Humans

KW - Infant

KW - Treatment Outcome

KW - Remission Induction

KW - Incidence

KW - Precursor Cell Lymphoblastic Leukemia-Lymphoma/drug therapy

KW - Child

KW - Cohort Studies

U2 - 10.1038/s41375-022-01540-1

DO - 10.1038/s41375-022-01540-1

M3 - Journal article

C2 - 35314777

VL - 36

SP - 1274

EP - 1282

JO - Leukemia

JF - Leukemia

SN - 0887-6924

IS - 5

ER -