Published Ahead of Print on June 14, 2018, as doi:10.3324/haematol.2018.191536. Copyright 2018 Ferrata Storti Foundation.
Genetics of acute myeloid leukemia in the elderly: mutation spectrum and clinical impact in intensively treated patients aged ≥ 75 years by Victoria V. Prassek, Maja Rothenberg-Thurley, Maria C. Sauerland, Tobias Herold, Hanna Janke, Bianka Ksienzyk, Nikola P. Konstandin, Dennis Goerlich, Utz Krug, Andreas Faldum, Wolfgang E. Berdel, Bernhard Wörmann, Jan Braess, Stephanie Schneider, Marion Subklewe, Stephan K. Bohlander, Wolfgang Hiddemann, Karsten Spiekermann and Klaus H. Metzeler Haematologica 2018 [Epub ahead of print] Citation: Victoria V. Prassek, Maja Rothenberg-Thurley, Maria C. Sauerland, Tobias Herold, Hanna Janke, Bianka Ksienzyk, Nikola P. Konstandin, Dennis Goerlich, Utz Krug, Andreas Faldum, Wolfgang E. Berdel, Bernhard Wörmann, Jan Braess, Stephanie Schneider, Marion Subklewe, Stephan K. Bohlander, Wolfgang Hiddemann, Karsten Spiekermann and Klaus H. Metzeler. Genetics of acute myeloid leukemia in the elderly: mutation spectrum and clinical impact in intensively treated patients aged ≥ 75 years. Haematologica. 2018; 103:xxx doi:10.3324/haematol.2018.191536 Publisher's Disclaimer. E-publishing ahead of print is increasingly important for the rapid dissemination of science. Haematologica is, therefore, E-publishing PDF files of an early version of manuscripts that have completed a regular peer review and have been accepted for publication. E-publishing of this PDF file has been approved by the authors. After having E-published Ahead of Print, manuscripts will then undergo technical and English editing, typesetting, proof correction and be presented for the authors' final approval; the final version of the manuscript will then appear in print on a regular issue of the journal. All legal disclaimers that apply to the journal also pertain to this production process.
Genetics of acute myeloid leukemia in the elderly: mutation spectrum and clinical impact in intensively treated patients aged ≥75 years Victoria V. Prassek1, Maja Rothenberg-Thurley1, Maria C. Sauerland2, Tobias Herold1,3,4, Hanna Janke1, Bianka Ksienzyk 1, Nikola P. Konstandin1, Dennis Goerlich2, Utz Krug5, Andreas Faldum2, Wolfgang E. Berdel2, Bernhard Wörmann6, Jan Braess7, Stephanie Schneider1, Marion Subklewe1, Stefan K. Bohlander8, Wolfgang Hiddemann1,3,4, Karsten Spiekermann1,3,4 and Klaus H. Metzeler1,3,4 1
Laboratory for Leukemia Diagnostics, Department of Medicine III, University Hospital, LMU Munich, Germany 2 Institute of Biostatistics and Clinical Research, University of Muenster, Muenster, Germany 3 German Cancer Consortium (DKTK), Partner Site Munich, Munich, Germany 4 German Cancer Research Center (DKFZ), Heidelberg, Germany 5 Hospital Leverkusen, Leverkusen, Germany 6 Charité – University Hospital Berlin, Berlin, Germany 7 Department of Oncology and Hematology, Hospital Barmherzige Brueder, Regensburg, Germany 8 Department of Molecular Medicine and Pathology, University of Auckland, Auckland, New Zealand
Running head: Genetics and outcomes in AML patients ≥75 years Address for Correspondence: Klaus H. Metzeler, MD Department of Medicine III University Hospital, LMU Munich Marchioninistrasse 15 81377 Muenchen Germany
[email protected]
Word count: 245 (abstract) / 3985 words (main text).
Prassek et al.
Genetics and outcomes in AML patients ≥75 years
Abstract (250 words) Acute myeloid leukemia is a disease of the elderly (median age at diagnosis, 65-70 years). The prognosis of older acute myeloid leukemia patients is generally poor. While genetic markers have become important tools for risk stratification and treatment selection in young and middle-aged patients, their applicability in very old patients is less clear. We sought to validate existing genetic risk classifications systems and identify additional factors associated with outcomes in intensively treated patients aged ≥75 years. In 151 patients who received induction chemotherapy in the AMLCG-1999 trial, we investigated recurrently mutated genes using a targeted sequencing assay covering 64 genes. The median number of mutated genes per patient was four. The most commonly mutated genes were TET2 (42%), DNMT3A (35%), NPM1 (32%), SRSF2 (25%) and ASXL1 (21%). The complete remission rate was 44% and the 3-year survival was 21% for the entire cohort. While adverse-risk cytogenetics (MRC classification) associated with shorter overall survival (p=0.001), NPM1 and FLT3-ITD mutations (present in 18%) had no significant impact on overall survival. Notably, none of the 13 IDH1 mutated patients (9%) reached complete remission. Consequently, the overall survival of this subgroup was significantly shorter than for IDH1 wildtype patients (p
