title: Prognostic significance of the European LeukemiaNet standardized system for reporting cytogenetic and molecular alterations in adults with acute myeloid leukemia.
abstract: OBJECTIVE
  To evaluate the prognostic significance of the international European LeukemiaNet (ELN) guidelines for reporting genetic alterations in acute myeloid leukemia (AML).
  
  
  METHODS
  We analyzed 1,550 adults with primary AML, treated on Cancer and Leukemia Group B first-line trials, who had pretreatment cytogenetics and, for cytogenetically normal patients, mutational status of NPM1, CEBPA, and FLT3 available. We compared complete remission (CR) rates, disease-free survival (DFS), and overall survival (OS) among patients classified into the four ELN genetic groups (favorable, intermediate-I, intermediate-II, adverse) separately for 818 younger (age < 60 years) and 732 older (age ≥ 60 years) patients.
  
  
  RESULTS
  The percentages of younger versus older patients in the favorable (41% v 20%; P < .001), intermediate-II (19% v 30%; P < .001), and adverse (22% v 31%; P < .001) genetic groups differed. The favorable group had the best and the adverse group the worst CR rates, DFS, and OS in both age groups. Both intermediate groups had significantly worse outcomes than the favorable but better than the adverse group. Intermediate-I and intermediate-II groups in older patients had similar outcomes, whereas the intermediate-II group in younger patients had better OS but not better CR rates or DFS than the intermediate-I group. The prognostic significance of ELN classification was confirmed by multivariable analyses. For each ELN group, older patients had worse outcomes than younger patients.
  
  
  CONCLUSIONS
  The ELN classification clearly separates the genetic groups by outcome, supporting its use for risk stratification in clinical trials. Because they have different proportions of genetic alterations and outcomes, younger and older patients should be reported separately when using the ELN classification.
authors.affiliation: The Ohio State University Comprehensive Cancer Center, Columbus, OH 43210-1228, USA. krzysztof.mrozek@osumc.edu
authors.forename: Krzysztof
authors.initials: K
authors.lastname: Mrózek
authors.forename: Guido
authors.initials: G
authors.lastname: Marcucci
authors.forename: Deedra
authors.initials: D
authors.lastname: Nicolet
authors.forename: Kati S
authors.initials: KS
authors.lastname: Maharry
authors.forename: Heiko
authors.initials: H
authors.lastname: Becker
authors.forename: Susan P
authors.initials: SP
authors.lastname: Whitman
authors.forename: Klaus H
authors.initials: KH
authors.lastname: Metzeler
authors.forename: Sebastian
authors.initials: S
authors.lastname: Schwind
authors.forename: Yue-Zhong
authors.initials: YZ
authors.lastname: Wu
authors.forename: Jessica
authors.initials: J
authors.lastname: Kohlschmidt
authors.forename: Mark J
authors.initials: MJ
authors.lastname: Pettenati
authors.forename: Nyla A
authors.initials: NA
authors.lastname: Heerema
authors.forename: AnneMarie W
authors.initials: AW
authors.lastname: Block
authors.forename: Shivanand R
authors.initials: SR
authors.lastname: Patil
authors.forename: Maria R
authors.initials: MR
authors.lastname: Baer
authors.forename: Jonathan E
authors.initials: JE
authors.lastname: Kolitz
authors.forename: Joseph O
authors.initials: JO
authors.lastname: Moore
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Carroll
authors.forename: Richard M
authors.initials: RM
authors.lastname: Stone
authors.forename: Richard A
authors.initials: RA
authors.lastname: Larson
authors.forename: Clara D
authors.initials: CD
authors.lastname: Bloomfield
mesh_terms: D000293:Adolescent; D000328:Adult; D000367:Age Factors; D000368:Aged; D000369:Aged, 80 and over; D002986:Clinical Trials as Topic; D003582:Cytogenetics; D018572:Disease-Free Survival; D005060:Europe; D005260:Female; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000235:genetics* / Q000628:therapy*; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D000090243:Nucleophosmin; D011379:Prognosis; D012074:Remission Induction; D012307:Risk Factors; D016896:Treatment Outcome; D055815:Young Adult