Clinical impact of gene mutations and lesions detected by SNP-array karyotyping in acute myeloid leukemia patients in the context of gemtuzumab ozogamicin treatment: results of the ALFA-0701 trial

We recently showed that the addition of fractionated doses of gemtuzumab ozogamicin (GO) to standard chemotherapy improves clinical outcome of acute myeloid leukemia (AML) patients. In the present study, we performed mutational analysis of 11 genes (FLT3, NPM1, CEBPA, MLL, WT1, IDH1/2, RUNX1, ASXL1,...

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Published in:Oncotarget 2014-02, Vol.5 (4), p.916-932
Main Authors: Renneville, Aline, Abdelali, Raouf Ben, Chevret, Sylvie, Nibourel, Olivier, Cheok, Meyling, Pautas, Cécile, Duléry, Rémy, Boyer, Thomas, Cayuela, Jean-Michel, Hayette, Sandrine, Raffoux, Emmanuel, Farhat, Hassan, Boissel, Nicolas, Terre, Christine, Dombret, Hervé, Castaigne, Sylvie, Preudhomme, Claude
Format: Article
Language:English
Subjects:
Aged
Aminoglycosides - therapeutic use
Antibodies, Monoclonal, Humanized - therapeutic use
Antineoplastic Agents - therapeutic use
Cohort Studies
Cytogenetics
Female
Humans
Karyotyping
Leukemia, Myeloid, Acute - drug therapy
Leukemia, Myeloid, Acute - genetics
Male
Middle Aged
Mutation
Polymorphism, Single Nucleotide
Prognosis
Research Paper
Risk Factors
Survival Analysis
Treatment Outcome
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Summary:We recently showed that the addition of fractionated doses of gemtuzumab ozogamicin (GO) to standard chemotherapy improves clinical outcome of acute myeloid leukemia (AML) patients. In the present study, we performed mutational analysis of 11 genes (FLT3, NPM1, CEBPA, MLL, WT1, IDH1/2, RUNX1, ASXL1, TET2, DNMT3A), EVI1 overexpression screening, and 6.0 single-nucleotide polymorphism array (SNP-A) analysis in diagnostic samples of the 278 AML patients enrolled in the ALFA-0701 trial. In cytogenetically normal (CN) AML (n=146), 38% of the patients had at least 1 SNP-A lesion and 89% of the patients had at least 1 molecular alteration. In multivariate analysis, the independent predictors of higher cumulative incidence of relapse were unfavorable karyotype (P = 0.013) and randomization in the control arm (P = 0.007) in the whole cohort, and MLL partial tandem duplications (P = 0.014) and DNMT3A mutations (P = 0.010) in CN-AML. The independent predictors of shorter overall survival (OS) were unfavorable karyotype (P
ISSN:1949-2553
1949-2553
DOI:10.18632/oncotarget.1536