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The prognostic impa...
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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- Öfverholm, Ingegerd (author)
- Karolinska Institutet
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- Rezayee, Fatemah (author)
- Karolinska Institutet
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- Heyman, Mats (author)
- Karolinska Institutet
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- Harila-Saari, Arja H. (author)
- Uppsala universitet,Barnonkologisk och neurologisk forskning,Department of Women's and Children's Health, Uppsala University, Uppsala, Sweden
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- Arvidsson, Linda (author)
- Lund Univ, Dept Lab Med, Div Clin Genet, Lund, Sweden.,Division of Clinical Genetics, Department of Laboratory Medicine, Lund University, Lund, Sweden
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- Schmiegelow, Kjeld (author)
- Rigshosp, Dept Paediat & Adolescent Med, Copenhagen, Denmark.;Univ Copenhagen, Inst Clin Med, Fac Med, Copenhagen, Denmark.,Department of Paediatrics and Adolescent Medicine, Rigshospitalet, Copenhagen, Denmark; Faculty of Medicine, Institute of Clinical Medicine, University of Copenhagen, Copenhagen, Denmark
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- Norén-Nyström, Ulrika (author)
- Umeå universitet,Pediatrik,Umeå Univ, Dept Clin Sci, Paediat, Umeå, Sweden.
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- Barbany, Gisela (author)
- Karolinska Institutet
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(creator_code:org_t)
- Wiley-Blackwell, 2023
- 2023
- English.
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In: British Journal of Haematology. - : Wiley-Blackwell. - 0007-1048 .- 1365-2141. ; 202:2, s. 384-392
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Abstract
Subject headings
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- 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.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Hematologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Hematology (hsv//eng)
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Cancer och onkologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Cancer and Oncology (hsv//eng)
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Pediatrik (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Pediatrics (hsv//eng)
Keyword
- IKZF1
- NOPHO
- paediatric acute lymphoblastic leukaemia
- prognostic marker
- risk stratification
Publication and Content Type
- ref (subject category)
- art (subject category)
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