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Leukemia. 2015 Nov;29(11):2154-61. doi: 10.1038/leu.2015.134. Epub 2015 Jun 8.

IKZF1 deletion is an independent prognostic marker in childhood B-cell precursor acute lymphoblastic leukemia, and distinguishes patients benefiting from pulses during maintenance therapy: results of the EORTC Children's Leukemia Group study 58951.

Author information

1
Department of Genetics, Robert Debré Hospital, APHP, Paris, France.
2
Hematology University Institute, Paris-Diderot University, Paris, France.
3
Centre de Biologie Pathologie PM Degand, INSERM U837, Lille, France.
4
Department of Hematology, Universitair Ziekenhuis Brussel, Vrije Universiteit Brussel (VUB), Brussels, Belgium.
5
EORTC Headquarters, Brussels, Belgium.
6
Department of Pediatric Hematology-Oncology, Ghent University Hospital, Ghent, Belgium.
7
Department of Cancer Biology, Institute of Genetics and Molecular and Cellular Biology (IGBMC), Illkirch, France.
8
Department of Pediatrics, Portuguese Oncology Institute, Porto, Portugal.
9
Department of Pediatric Onco-Hematology, Hôpital Universitaire des Enfants Reine Fabiola (ULB), Brussels, Belgium.
10
Department of Hematology, Hautepierre University Hospital, Strasbourg, France.
11
Department of Pediatric Hematology-Oncology, Lille University Hospital, Lille, France.
12
Department of Hematology, J Bernard University Hospital, Poitiers, France.
13
Department of Pediatric Onco-Hematology, Grenoble University Hospital, La Tronche, France.
14
Department of Pediatric Onco-Hematology, Purpan University Hospital, Toulouse, France.
15
Department of Pediatric Onco-Hematology, Besançon University Hospital, Besançon, France.
16
Department of Pediatric Onco-Hematology, Nice University Hospital, Nice, France.
17
Department of Pediatric Onco-Hematology, Montpellier University Hospital, Montpellier, France.
18
Department of Pediatrics, University Hospital Gasthuisberg, Leuven, Belgium.
19
Department of Pediatric Hematology, Robert Debré Hospital, APHP, Paris, France.
20
Hematology Laboratory, IHOP, Lyon, France.
21
Hematology Laboratory, University Hospital Purpan, Toulouse, France.
22
Department of Pediatric Hematology, IHOP and Claude Bernard University, Lyon, France.

Abstract

The added value of IKZF1 gene deletion (IKZF1(del)) as a stratifying criterion in B-cell precursor acute lymphoblastic leukemia (BCP-ALL) is still debated. We performed a comprehensive analysis of the impact of IKZF1(del) in a large cohort of children (n=1223) with BCR-ABL1-negative BCP-ALL treated in the EORTC-CLG trial 58951. Patients with IKZF1(del) had a lower 8-year event-free survival (EFS, 67.7% versus 86.5%; hazard ratio (HR)=2.41; 95% confidence interval (CI)=1.75-3.32; P<0.001). Importantly, despite association with high-risk features such as high minimal residual disease, IKZF1(del) remained significantly predictive in multivariate analyses. Analysis by genetic subtype showed that IKZF1(del) increased risk only in the high hyperdiploid ALLs (HR=2.57; 95% CI=1.19-5.55; P=0.013) and in 'B-other' ALLs, that is, lacking classifying genetic lesions (HR=2.22; 95% CI=1.45-3.39; P<0.001), the latter having then a dramatically low 8-year EFS (56.4; 95% CI=44.6-66.7). Among IKZF1(del)-positive patients randomized for vincristine-steroid pulses during maintenance, those receiving pulses had a significantly higher 8-year EFS (93.3; 95% CI=61.3-99.0 versus 42.1; 95% CI=20.4-62.5). Thus, IKZF1(del) retains independent prognostic significance in the context of current risk-adapted protocols, and is associated with a dismal outcome in 'B-other' ALL. Addition of vincristine-steroid pulses during maintenance may specifically benefit to IKZF1(del) patients in preventing relapses.

TRIAL REGISTRATION:

ClinicalTrials.gov NCT00003728.

PMID:
26050650
DOI:
10.1038/leu.2015.134
[Indexed for MEDLINE]

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