title: Karyotype plus NPM1 mutation status defines a group of elderly patients with AML (≥60 years) who benefit from intensive post-induction consolidation therapy.
abstract: Although it is generally appreciated that a subset of elderly patients with acute myeloid leukemia (AML) may benefit from intensive consolidation, little is known about variables predicting such benefit. We analyzed 192 consecutive patients with de novo AML aged ≥60 years who were treated with intensive chemotherapy. About 115 patients (60%) achieved complete hematologic remission (CR). Among several parameters, the karyotype was the only independent variable predicting CR (P < 0.05). About 92% (105/115) of the CR-patients received up to four consolidation cycles of intermediate dose ARA-C. Median continuous CR (CCR) and disease-free survival (DFS) were 1.3 and 1.1 years, respectively. CCR, DFS, and survival at 5 years were 23%, 18%, and 15%, respectively. Only karyotype and mutated NPM1 (NPM1mut) were independent predictors of survival. NPM1mut showed a particular prognostic impact in patients with normal (CN) or non-monosomal (Mkneg) karyotype by Haemato-Oncology Foundation for Adults in the Netherlands (HOVON)-criteria, or intermediate karyotype by Southwest Oncology Group (SWOG)-criteria. The median CCR was 0.94, 1.6, 0.9, and 0.5 years for core-binding-factor, CN/Mkneg-NPM1mut, CN/Mkneg-NPM1-wild-type AML, and AML with monosomal karyotype, respectively, and the 5-year survival was 25%, 39%, 2%, and 0%, respectively (P < 0.05). Similar results (0.9, 1.5, 0.9, and 0.5 years) were obtained using modified SWOG criteria and NPM1 mutation status (P < 0.05). In summary, elderly patients with CN/Mkneg-NPM1mut or CBF AML can achieve long term CCR when treated with intensive induction and consolidation therapy whereas most elderly patients with CN/Mkneg-NPM1wt or Mkpos AML may not benefit from intensive chemotherapy. For these patients either hematopoietic-stem-cell-transplantation or alternative treatments have to be considered. Am. J. Hematol. 91:1239-1245, 2016. © 2016 Wiley Periodicals, Inc.
authors.affiliation: Department of Internal Medicine I, Division of Hematology and Hemostaseology, Medical University of Vienna, Vienna, Austria.|Ludwig Boltzmann Cluster Oncology, Medical University of Vienna, Vienna, Austria.
authors.forename: Wolfgang R
authors.initials: WR
authors.lastname: Sperr
authors.affiliation: Department of Internal Medicine I, Hospital of the Elisabethinen, Linz, Austria.
authors.forename: Otto
authors.initials: O
authors.lastname: Zach
authors.affiliation: Department of Internal Medicine I, Hospital of the Elisabethinen, Linz, Austria.
authors.forename: Iris
authors.initials: I
authors.lastname: Pöll
authors.affiliation: Department of Internal Medicine I, Division of Hematology and Hemostaseology, Medical University of Vienna, Vienna, Austria.|Ludwig Boltzmann Cluster Oncology, Medical University of Vienna, Vienna, Austria.
authors.forename: Susanne
authors.initials: S
authors.lastname: Herndlhofer
authors.affiliation: Department of Internal Medicine I, Division of Hematology and Hemostaseology, Medical University of Vienna, Vienna, Austria.
authors.forename: Paul
authors.initials: P
authors.lastname: Knoebl
authors.affiliation: Department of Internal Medicine I, Hospital of the Elisabethinen, Linz, Austria.
authors.forename: Ansgar
authors.initials: A
authors.lastname: Weltermann
authors.affiliation: Department of Obstetrics and Gynecology, Medical University of Vienna, Vienna, Austria.
authors.forename: Berthold
authors.initials: B
authors.lastname: Streubel
authors.affiliation: Department of Internal Medicine I, Division of Hematology and Hemostaseology, Medical University of Vienna, Vienna, Austria.|Ludwig Boltzmann Cluster Oncology, Medical University of Vienna, Vienna, Austria.
authors.forename: Ulrich
authors.initials: U
authors.lastname: Jaeger
authors.affiliation: Institute of Environmental Health, Medical University of Vienna, Vienna, Austria.
authors.forename: Michael
authors.initials: M
authors.lastname: Kundi
authors.affiliation: Department of Internal Medicine I, Division of Hematology and Hemostaseology, Medical University of Vienna, Vienna, Austria.|Ludwig Boltzmann Cluster Oncology, Medical University of Vienna, Vienna, Austria.
authors.forename: Peter
authors.initials: P
authors.lastname: Valent
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D060830:Consolidation Chemotherapy / Q000379:methods*; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D060828:Induction Chemotherapy; D059785:Karyotype; D015470:Leukemia, Myeloid, Acute / Q000175:diagnosis* / Q000188:drug therapy* / Q000235:genetics / Q000401:mortality; D008875:Middle Aged; D009154:Mutation; D009426:Netherlands; D009687:Nuclear Proteins / Q000235:genetics*; D000090243:Nucleophosmin; D011379:Prognosis; D012074:Remission Induction / Q000379:methods; D016019:Survival Analysis
chemical_list: C000716967:NPM1 protein, human; D009687:Nuclear Proteins; D000090243:Nucleophosmin