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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 Chrildren's Leukemia Group study 58951

(2015) LEUKEMIA. 29(11). p.2154-2161
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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(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.
Keywords
GENETIC ALTERATIONS, MINIMAL RESIDUAL DISEASE, RANDOMIZED-TRIAL, ERG DELETION, RISK, EXPRESSION, DEXAMETHASONE, VINCRISTINE, INDUCTION, RELAPSE

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Chicago
Clappier, E, N Grardel, M Bakkus, J Rapion, Barbara De Moerloose, P Kastner, A Caye, et al. 2015. “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 Chrildren’s Leukemia Group Study 58951.” Leukemia 29 (11): 2154–2161.
APA
Clappier, E., Grardel, N., Bakkus, M., Rapion, J., De Moerloose, B., Kastner, P., Caye, A., et al. (2015). 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 Chrildren’s Leukemia Group study 58951. LEUKEMIA, 29(11), 2154–2161.
Vancouver
1.
Clappier E, Grardel N, Bakkus M, Rapion J, De Moerloose B, Kastner P, et al. 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 Chrildren’s Leukemia Group study 58951. LEUKEMIA. 2015;29(11):2154–61.
MLA
Clappier, E et al. “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 Chrildren’s Leukemia Group Study 58951.” LEUKEMIA 29.11 (2015): 2154–2161. Print.
@article{6884683,
  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(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.},
  author       = {Clappier, E and Grardel, N and Bakkus, M and Rapion, J and De Moerloose, Barbara and Kastner, P and Caye, A and Vivent, J and Costa, V and Ferster, A and Lutz, P and Mazingue, F and Millot, F and Plantaz, D and Plat, G and Plouvier, E and Poirée, M and Sirvent, N and Uyttebroeck, A and Yakouben, K and Girard, S and Dastugue, N and Suciu, S and Benoit, Yves and Bertrand, Y and Cavé, H},
  issn         = {0887-6924},
  journal      = {LEUKEMIA},
  keywords     = {GENETIC ALTERATIONS,MINIMAL RESIDUAL DISEASE,RANDOMIZED-TRIAL,ERG DELETION,RISK,EXPRESSION,DEXAMETHASONE,VINCRISTINE,INDUCTION,RELAPSE},
  language     = {eng},
  number       = {11},
  pages        = {2154--2161},
  title        = {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 Chrildren's Leukemia Group study 58951},
  url          = {http://dx.doi.org/10.1038/leu.2015.134},
  volume       = {29},
  year         = {2015},
}

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