• Citer

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.

par Clappier, E;Grardel, Nathalie;Bakkus, M;Rapion, J;De Moerloose, B;Kastner, Philippe;Caye, A;Vivent, Jocelyne;Costa, V;Ferster, Alina ;Lutz, P;Mazingue, F;Millot, Frédéric;Plantaz, D;Plat, G;Plouvier, Emmanuel;Poirée, Marilyne;Sirvent, Nicolas;Uyttebroeck, Anne;Yakouben, Karima;Girard, S;Dastugue, Nicole;Suciu, S;Benoît, Yves;Bertrand, Yves;Cavé, H;Children’s Leukemia Group (CLG) of the European Organisation for Research and Treatment of Cancer (EORTC),
Référence Leukemia, 29, 11, page (2154-2161)
Publication Publié, 2015-11

Article révisé par les pairs

• Détails
• Contenu

Résumé :

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.