The prognostic value of IKZF1<sup>plus</sup> in B‐cell progenitor acute lymphoblastic leukemia: Results from the EORTC 58951 trial
Michal Kiciński, Chloé Arfeuille, Nathalie Grardel, Marleen Bâkkus, Aurélie Caye‐Eude, Geneviève Plat, Alina Ferster, Anne Uyttebroeck, Barbara De Moerloose, Pierre‐Simon Rohrlich, Stefan Suciu, Yves Bertrand, Hélène Cavé
Abstract
Abstract Background IKZF1 gene deletion is an indicator of poor prognosis in childhood B‐cell precursor acute lymphoblastic leukemia (BCP‐ALL). The AEIOP/BFM group proposed that the prognostic strength of IKZF1 deletion could be remarkably improved by taking into account additional genetic deletions and reported that among patients with an IKZF1 deletion those with deletions in CDKN2A/2B , PAX5 , or PAR1 in the absence of ERG deletion, grouped as IKZF1 plus , had the worst outcome. Procedure Between 1998 and 2008, 1636 patients under 18 years of age with previously untreated BCP‐ALL were registered in the EORTC 58951 trial. Those with multiplex ligation‐dependent probe amplification data were included in this analysis. Unadjusted and adjusted Cox model was used to investigate the additional prognostic value of IKZF1 plus . Results Among 1200 patients included in the analysis, 1039 (87%) had no IKZF1 deletion (IKZF1 WT ), 87 (7%) had an IKZF1 deletion but not IKZF1 plus (IKZF1 del ) and 74 (6%) had IKZF1 plus . In the unadjusted analysis, both patients with IKZF1 del (hazard ratio [HR] = 2.10, 95% confidence interval [CI]: 1.34–3.31) and IKZF1 plus (HR = 3.07, 95% CI: 2.01–4.67) had a shorter event‐free survival compared with IKZF1 WT . However, although the IKZF1 plus status was associated with patients’ characteristics indicating poor prognosis, the difference between IKZF1 plus and IKZF1 del was not statistically significant (HR = 1.46, 95% CI: 0.83–2.57, p = .19). The results of the adjusted analysis were similar to the unadjusted analysis. Conclusions In patients with BCP‐ALL from the EORTC 58951 trial, the improvement of the prognostic importance of IKZF1 by considering IKZF1 plus was not statistically significant.