Minimal residual disease, long-term outcome, and IKZF1 deletions in children and adolescents with Down syndrome and acute lymphocytic leukaemia: a matched cohort study

• Published in: The Lancet Haematology
• Main Authors: Michels, Naomi, Boer, Judith M, Enshaei, Amir, Sutton, Rosemary, Heyman, Mats, Ebert, Sabine, Fiocco, Marta, de Groot-Kruseman, Hester A, van der Velden, Vincent H J, Barbany, Gisela, Escherich, Gabriele, Vora, Ajay, Trahair, Toby, Dalla-Pozza, Luciano, Pieters, Rob, zur Stadt, Udo, Schmiegelow, Kjeld, Moorman, Anthony V, Zwaan, C Michel, den Boer, Monique L
• Format: Text
• Language: English
• Published: Elsevier Ltd 2021
• Subjects: Articles; Norway; Iceland
• Online Access: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8480280/; http://www.ncbi.nlm.nih.gov/pubmed/34560013; https://doi.org/10.1016/S2352-3026(21)00272-6

BACKGROUND: Patients with Down syndrome and acute lymphocytic leukaemia are at an increased risk of treatment-related mortality and relapse, which is influenced by unfavourable genetic aberrations (eg, IKZF1 deletion). We aimed to investigate the potential underlying effect of Down syndrome versus the effects of adverse cancer genetics on clinical outcome. METHOD: Patients (aged 1–23 years) with Down syndrome and acute lymphocytic leukaemia and matched non-Down syndrome patients with acute lymphocytic leukaemia (matched controls) from eight trials (DCOG ALL10 and ALL11, ANZCHOG ALL8, AIEOP-BFM ALL2009, UKALL2003, NOPHO ALL2008, CoALL 07-03, and CoALL 08-09) done between 2002 and 2018 across various countries (the Netherlands, the UK, Australia, Denmark, Finland, Iceland, Norway, Sweden, and Germany) were included. Participants were matched (1:3) for clinical risk factors and genetics, including IKZF1 deletion. The primary endpoint was the comparison of MRD levels (absolute MRD levels were categorised into two groups, low [<0·0001] and high [≥0·0001]) between patients with Down syndrome and acute lymphocytic leukaemia and matched controls, and the secondary outcomes were comparison of long-term outcomes (event-free survival, overall survival, relapse, and treatment-related mortality [TRM]) between patients with Down syndrome and acute lymphocytic leukaemia and matched controls. Two matched cohorts were formed: for MRD analyses and for long-term outcome analyses. For both cohorts, matching was based on induction regimen; for the long-term outcome cohort, matching also included MRD-guided treatment group. We used mixed-effect models, Cox models, and competing risk for statistical analyses. FINDINGS: Of 251 children and adolescents with Down syndrome and acute lymphocytic leukaemia, 136 were eligible for analyses and matched to 407 (of 8426) non-Down syndrome patients with acute lymphocytic leukaemia (matched controls). 113 patients with Down syndrome and acute lymphocytic leukaemia were excluded from matching in ...