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

Öfverholm, Ingegerd ; Rezayee, Fatemah ; Heyman, Mats ; Harila, Arja ; Arvidsson, Linda ; Schmiegelow, Kjeld ; Norén-Nyström, Ulrika and Barbany, Gisela (2023) In British Journal of Haematology 202(2). p.384-392
Abstract

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... (More)

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.

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author
; ; ; ; ; ; and
publishing date
type
Contribution to journal
publication status
published
subject
keywords
IKZF1, NOPHO, paediatric acute lymphoblastic leukaemia, prognostic marker, risk stratification
in
British Journal of Haematology
volume
202
issue
2
pages
9 pages
publisher
Wiley-Blackwell
external identifiers
  • pmid:37156607
  • scopus:85158074940
ISSN
0007-1048
DOI
10.1111/bjh.18852
language
English
LU publication?
no
id
c5cd9a98-c0c3-442d-8019-43fc3bd3776f
date added to LUP
2023-08-16 11:21:20
date last changed
2024-04-20 00:44:25
@article{c5cd9a98-c0c3-442d-8019-43fc3bd3776f,
  abstract     = {{<p>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.</p>}},
  author       = {{Öfverholm, Ingegerd and Rezayee, Fatemah and Heyman, Mats and Harila, Arja and Arvidsson, Linda and Schmiegelow, Kjeld and Norén-Nyström, Ulrika and Barbany, Gisela}},
  issn         = {{0007-1048}},
  keywords     = {{IKZF1; NOPHO; paediatric acute lymphoblastic leukaemia; prognostic marker; risk stratification}},
  language     = {{eng}},
  number       = {{2}},
  pages        = {{384--392}},
  publisher    = {{Wiley-Blackwell}},
  series       = {{British Journal of Haematology}},
  title        = {{The prognostic impact of IKZF1 deletions and UKALL genetic classifiers in paediatric B-cell precursor acute lymphoblastic leukaemia treated according to NOPHO 2008 protocols}},
  url          = {{http://dx.doi.org/10.1111/bjh.18852}},
  doi          = {{10.1111/bjh.18852}},
  volume       = {{202}},
  year         = {{2023}},
}