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

被引：87

作者：

Clappier, E. ^{[1
,2
]}

Grardel, N. ^{[3
]}

Bakkus, M. ^{[4
]}

Rapion, J. ^{[5
]}

De Moerloose, B. ^{[6
]}

Kastner, P. ^{[7
]}

Caye, A. ^{[1
,2
]}

Vivent, J. ^{[1
,2
]}

Costa, V. ^{[8
]}

Ferster, A. ^{[9
]}

Lutz, P. ^{[10
]}

Mazingue, F. ^{[11
]}

Millot, F. ^{[12
]}

Plantaz, D. ^{[13
]}

Plat, G. ^{[14
]}

Plouvier, E. ^{[15
]}

Poiree, M. ^{[16
]}

Sirvent, N. ^{[17
]}

Uyttebroeck, A. ^{[18
]}

Yakouben, K. ^{[19
]}

Girard, S. ^{[20
]}

Dastugue, N. ^{[21
]}

Suciu, S. ^{[5
]}

Benoit, Y. ^{[6
]}

Bertrand, Y. ^{[22
,23
]}

Cave, H. ^{[1
,2
]}

机构：

[1] Robert Debre Hosp, APHP, Dept Genet, F-75019 Paris, France

[2] Paris Diderot Univ, Hematol Univ Inst, Paris, France

[3] Ctr Biol Pathol PM Degand, INSERM, U837, Lille, France

[4] Vrije Univ Brussel, Univ Ziekenhuis Brussel, Dept Hematol, Brussels, Belgium

[5] EORTC Headquarters, Brussels, Belgium

[6] Ghent Univ Hosp, Dept Pediat Hematol Oncol, Ghent, Belgium

[7] IGBMC, Dept Canc Biol, Illkirch Graffenstaden, France

[8] Portuguese Oncol Inst, Dept Pediat, Oporto, Portugal

[9] Hop Univ Enfants Reine Fabiola ULB, Dept Pediat Oncohematol, Brussels, Belgium

[10] Hautepierre Univ Hosp, Dept Hematol, Strasbourg, France

[11] Lille Univ Hosp, Dept Pediat Hematol Oncol, Lille, France

[12] J Bernard Univ Hosp, Dept Hematol, Poitiers, France

[13] Grenoble Univ Hosp, Dept Pediat Oncohematol, La Tronche, France

[14] Purpan Univ Hosp, Dept Pediat Oncohematol, Toulouse, France

[15] Besancon Univ Hosp, Dept Pediat Oncohematol, Besancon, France

[16] Nice Univ Hosp, Dept Pediat Oncohematol, Nice, France

[17] Montpellier Univ Hosp, Dept Pediat Oncohematol, Montpellier, France

[18] Univ Hosp Gasthuisberg, Dept Pediat, Leuven, Belgium

[19] Robert Debre Hosp, APHP, Dept Pediat Hematol, Paris, France

[20] IHOP, Hematol Lab, Lyon, France

[21] Univ Hosp Purpan, Hematol Lab, Toulouse, France

[22] IHOP, Dept Pediat Hematol, Lyon, France

[23] Univ Lyon 1, F-69365 Lyon, France

来源：

LEUKEMIA | 2015年 / 29卷 / 11期

关键词：

MINIMAL RESIDUAL DISEASE; GENETIC ALTERATIONS; RANDOMIZED-TRIAL; ERG DELETION; RISK; EXPRESSION; DEXAMETHASONE; VINCRISTINE; INDUCTION; RELAPSE;

D O I：

10.1038/leu.2015.134

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

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(de)l 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.

引用

页码：2154 / 2161

页数：8

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