Michael Lübbert, Karina Eiwen, Gerrit Jan Schuurhuis, Brigitte Schlegelberger, Claudia Erpelinck, Jan Engelmann, Arnold Ganser, Veronika Rockova, Hartmut Döhner, Mario Bargetzi, Ulrich Germing, H. Berna Beverloo, Ruud Delwel, Peter Vandenberghe, Peter J. M. Valk, Veronica Teleanu, Stefan Gröschel, Ingo G.H. Schmidt-Wolf, Richard F. Schlenk, Jürgen Krauter, Bob Löwenberg, Marije Havermans, Edo Vellenga, Leo F. Verdonck, Thomas Pabst, Gert J. Ossenkoppele, Gregor Verhoef, Michael W.M. Kühn, Konstanze Döhner, Hematology laboratory, Hematology, CCA - Disease profiling, Faculteit Medische Wetenschappen/UMCG, Guided Treatment in Optimal Selected Cancer Patients (GUTS), Stem Cell Aging Leukemia and Lymphoma (SALL), Epidemiology, and Clinical Genetics
Purpose To evaluate the prognostic value of ecotropic viral integration 1 gene (EVI1) overexpression in acute myeloid leukemia (AML) with MLL gene rearrangements. Patients and Methods We identified 286 patients with AML with t(11q23) enrolled onto German-Austrian Acute Myeloid Leukemia Study Group and Dutch-Belgian-Swiss Hemato-Oncology Cooperative Group prospective treatment trials. Material was available from 177 AML patients for EVI1 expression analysis. Results We divided 286 MLL-rearranged AMLs into three subgroups: t(9;11)(p22;q23) (44.8%), t(6;11)(q27;q23) (14.7%), and t(v;11q23) (40.5%). EVI1 overexpression (EVI1+) was found in 45.8% of all patients with t(11q23), with t(6;11) showing the highest frequency (83.9%), followed by t(9;11) at 40.0%, and t(v;11q23) at 34.8%. Concurrent gene mutations were rare or absent in all three subgroups. Within all t(11q23) AMLs, EVI1+ was the sole prognostic factor, predicting for inferior overall survival (OS; hazard ratio [HR], 2.06; P = .003), relapse-free survival (HR, 2.28; P = .002), and event-free survival (HR, 1.79; P = .009). EVI1+ AMLs with t(11q23) in first complete remission (CR) had a significantly better outcome after allogeneic transplantation compared with other consolidation therapies (5-year OS, 54.7% v 0%; Mantel-Byar, P = .0006). EVI1− t(9;11) AMLs had lower WBC counts, more commonly FAB M5 morphology, and frequently had additional trisomy 8 (39.6%; P < .001). Among t(9;11) AMLs, EVI1+ again was the sole independent adverse prognostic factor for survival. Conclusion Deregulated EVI1 expression defines poor prognostic subsets among AML with t(11q23) and AML with t(9;11)(p22;q23). Patients with EVI1+ MLL-rearranged AML seem to benefit from allogeneic transplantation in first CR.