Link to the University of Pittsburgh Homepage
Link to the University Library System Homepage Link to the Contact Us Form

A modified integrated genetic model for risk prediction in younger patients with acute myeloid leukemia

Sloan, CE and Luskin, MR and Boccuti, AM and Sehgal, AR and Zhao, J and Daber, RD and Morrissette, JJD and Luger, SM and Bagg, A and Gimotty, PA and Carroll, M (2016) A modified integrated genetic model for risk prediction in younger patients with acute myeloid leukemia. PLoS ONE, 11 (4).

[img]
Preview
PDF
Published Version
Available under License : See the attached license file.

Download (1MB)
[img] Plain Text (licence)
Available under License : See the attached license file.

Download (1kB)

Abstract

© 2016 Sloan et al. T. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Background: Although cytogenetics-based prognostication systems are well described in acute myeloid leukemia (AML), overall survival (OS) remains highly variable within risk groups. An integrated genetic prognostic (IGP) model using cytogenetics plus mutations in nine genes was recently proposed for patients ≤60 years to improve classification. This model has not been validated in clinical practice. Methods and Findings: We retrospectively studied 197 patients with newly diagnosed de novo AML. We compared OS curves among the mutational profiles defined by the IGP model. The IGP model assigned patients with intermediate cytogenetics as having favorable, intermediate or unfavorable mutational profiles. The IGP model reassigned 50 of 137 patients with intermediate cytogenetics to favorable or unfavorable mutational profiles. Median OS was 2.8 years among 14 patients with intermediate cytogenetics and favorable mutational profiles (mutant NPM1 and mutant IDH1 or IDH2) and 1.3 years among patients with intermediate mutational profiles. Among patients with intermediate cytogenetics labeled as having unfavorable mutational profiles, median OS was 0.8 years among 24 patients with FLT3-ITD positive AML and high-risk genetic changes (trisomy 8, TET2 and/or DNMT3A) and 1.7 years among 12 patients with FLT3-ITD negative AML and high-risk mutations (TET2, ASXL1 and/or PHF6). OS for patients with intermediate cytogenetics and favorable mutational profiles was similar to OS for patients with favorable cytogenetics (p = 0.697) and different from patients with intermediate cytogenetics and intermediate mutational profiles (p = 0.028). OS among patients with FLT3-ITD positive AML and high-risk genetic changes was similar to patients with unfavorable cytogenetics (p = 0.793) and different from patients with intermediate IGP profile (p = 0.022). Patients with FLT3-ITD negative AML and high-risk mutations, defined as 'unfavorable' in the IGP model, had OS similar to patients with intermediate IGP profile (p = 0.919). Conclusions: The IGP model was not completely validated in our cohort. However, mutations in six out of the nine genes can be used to characterize survival (NPMI, IDH1, IDH2, FLT3-ITD, TET2, DNMT3A) and allow for more robust prognostication in the patients who are re-categorized by the IGP model. These mutations should be incorporated into clinical testing for younger patients outside of clinical trials, in order to guide therapy.


Share

Citation/Export:
Social Networking:
Share |

Details

Item Type: Article
Status: Published
Creators/Authors:
CreatorsEmailPitt UsernameORCID
Sloan, CE
Luskin, MR
Boccuti, AM
Sehgal, AR
Zhao, J
Daber, RD
Morrissette, JJD
Luger, SM
Bagg, A
Gimotty, PA
Carroll, M
Contributors:
ContributionContributors NameEmailPitt UsernameORCID
EditorMills, KenUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Date: 1 April 2016
Date Type: Publication
Access Restriction: No restriction; Release the ETD for access worldwide immediately.
Journal or Publication Title: PLoS ONE
Volume: 11
Number: 4
DOI or Unique Handle: 10.1371/journal.pone.0153016
Institution: University of Pittsburgh
Refereed: Yes
Date Deposited: 25 Aug 2016 17:20
Last Modified: 02 Feb 2019 13:58
URI: http://d-scholarship.pitt.edu/id/eprint/28275

Metrics

Monthly Views for the past 3 years

Plum Analytics

Altmetric.com


Actions (login required)

View Item View Item