High EVI1 Expression Predicts Outcome in Younger Adult Patients With Acute Myeloid Leukemia and Is Associated With Distinct Cytogenetic Abnormalities

S Groschel, Sanne Lugthart, RF Schlenk, Peter Valk, K Eiwen, Chantal Goudswaard, WJL van Putten, S Kayser, LF Verdonck, M Lubbert, GJ Ossenkoppele, U Germing, I Schmidt-Wolf, B Schlegelberger, J Krauter, A Ganser, H Dohner, Bob Löwenberg, K Dohner, Ruud Delwel

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Abstract

Purpose The purpose of this study was to investigate frequency and prognostic significance of high EVI1 expression in acute myeloid leukemia (AML). Patients and Methods A diagnostic assay detecting multiple EVI1 splice variants was developed to determine the relative EVI1 expression by single real-time quantitative polymerase chain reaction in 1,382 newly diagnosed adult patients with AML younger than 60 years. Patients were treated on four Dutch-Belgian HOVON (n = 458) and two German-Austrian AML Study Group protocols (n = 924). Results The EVI1 assay was tested in the HOVON cohort and validated in the AMLSG cohort. High EVI1 levels (EVI1(+)) were found with similar frequencies in both cohorts combined, with a 10.7% incidence (148 of 1,382). EVI1(+) independently predicted low complete remission (CR) rate (odds ratio, 0.54; P = .002), adverse relapse-free survival (RFS; hazard ratio [HR], 1.32; P = .05), and event-free survival (EFS; HR, 1.46; P < .001). This adverse prognostic impact was more pronounced in the intermediate cytogenetic risk group (EFS; HR, 1.64; P < .001; and RFS; HR, 1.55; P = .02), and was also apparent in cytogenetically normal AML (EFS; HR, 1.67; P = .008). Besides inv(3)/t(3; 3), EVI1(+) was significantly associated with chromosome abnormalities monosomy 7 and t(11q23), conferring prognostic impact within these two cytogenetic subsets. EVI1(+) was virtually absent in favorable-risk AML and AML with NPM1 mutations. Patients with EVI1(+) AML (n = 28) who received allogeneic stem cell transplantation in first CR had significantly better 5-year RFS (33% +/- 10% v 0%). Conclusion EVI1 expression in AML is unequally distributed in cytogenetic subtypes. It predicts poor outcome, particularly among intermediate cytogenetic risk AML. Patients with EVI1(+) AML may benefit from allogeneic transplantation in first CR. Pretreatment EVI1 screening should be included in risk stratification. J Clin Oncol 28: 2101-2107. (C) 2010 by American Society of Clinical Oncology
Original languageUndefined/Unknown
Pages (from-to)2101-2107
Number of pages7
JournalJournal of Clinical Oncology
Volume28
Issue number12
Publication statusPublished - 2010

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