The prognostic impact of IKZF1 deletions and UKALL genetic classifiers in paediatric B-cell precursor acute lymphoblastic leukaemia treated according to NOPHO 2008 protocols

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  • Ingegerd Öfverholm
  • Fatemah Rezayee
  • Mats Heyman
  • Arja Harila
  • Linda Arvidsson
  • Schmiegelow, K.
  • Ulrika Norén-Nyström
  • Gisela Barbany

We investigated 390 paediatric B-cell precursor acute lymphoblastic leukaemia (BCP-ALL) patients treated according to NOPHO ALL 2008, regarding copy number alterations (CNA) of eight loci associated with adverse prognosis, including IKZF1. The impact on outcome was investigated for each locus individually, combined as CNA profiles and together with cytogenetic information. The presence of IKZF1 deletion or a poor-risk CNA profile was associated with poor outcome in the whole cohort. In the standard-risk group, IKZF1-deleted cases had an inferior probability of relapse-free survival (pRFS) (p ≤ 0.001) and overall survival (pOS) (p ≤ 0.001). Additionally, among B-other patients, IKZF1 deletion correlated with poor pRFS (60% vs. 90%) and pOS (65% vs. 89%). Both IKZF1 deletion and a poor-risk CNA profile were independent factors for relapse and death in multivariable analyses adjusting for known risk factors including measurable residual disease. Our data indicate that BCP-ALL patients with high-risk CNA or IKZF1 deletion have worse prognosis despite otherwise low-risk features. Conversely, patients with both a good CNA and cytogenetic profile had a superior relapse-free (p ≤ 0.001) and overall survival (p ≤ 0.001) in the cohort, across all risk groups. Taken together, our findings highlight the potential of CNA assessment to refine stratification in ALL.

Original languageEnglish
JournalBritish Journal of Haematology
Volume202
Issue number2
Pages (from-to)384-392
Number of pages9
ISSN0007-1048
DOIs
Publication statusPublished - 2023

Bibliographical note

Funding Information:
We acknowledge the support from the Swedish Childhood Cancer Fund (Barncancerfonden) through grants TJ 20150047, PR 2019‐0072 and KF2018‐0014. This work is part of the Danish nation‐wide research programme Childhood Oncology Network Targeting Research, Organization & Life expectancy (CONTROL) and supported by the Danish Cancer Society (R‐257‐A14720) and the Danish Childhood Cancer Foundation (2019‐5934 and 2020‐5769).

Publisher Copyright:
© 2023 The Authors. British Journal of Haematology published by British Society for Haematology and John Wiley & Sons Ltd.

    Research areas

  • IKZF1, NOPHO, paediatric acute lymphoblastic leukaemia, prognostic marker, risk stratification

ID: 373509904