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A Modified Integrated Genetic Model for Risk Prediction in Younger Patients with Acute Myeloid Leukemia.

Publication ,  Journal Article
Sloan, CE; Luskin, MR; Boccuti, AM; Sehgal, AR; Zhao, J; Daber, RD; Morrissette, JJD; Luger, SM; Bagg, A; Gimotty, PA; Carroll, M
Published in: PLoS One
2016

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.

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Published In

PLoS One

DOI

EISSN

1932-6203

Publication Date

2016

Volume

11

Issue

4

Start / End Page

e0153016

Location

United States

Related Subject Headings

  • Young Adult
  • Risk Factors
  • Retrospective Studies
  • Prognosis
  • Nucleophosmin
  • Models, Genetic
  • Middle Aged
  • Male
  • Leukemia, Myeloid, Acute
  • Humans
 

Citation

APA
Chicago
ICMJE
MLA
NLM
Sloan, C. E., Luskin, M. R., Boccuti, A. M., Sehgal, A. R., Zhao, J., Daber, R. D., … Carroll, M. (2016). A Modified Integrated Genetic Model for Risk Prediction in Younger Patients with Acute Myeloid Leukemia. PLoS One, 11(4), e0153016. https://doi.org/10.1371/journal.pone.0153016
Sloan, Caroline E., Marlise R. Luskin, Anne M. Boccuti, Alison R. Sehgal, Jianhua Zhao, Robert D. Daber, Jennifer J. D. Morrissette, et al. “A Modified Integrated Genetic Model for Risk Prediction in Younger Patients with Acute Myeloid Leukemia.PLoS One 11, no. 4 (2016): e0153016. https://doi.org/10.1371/journal.pone.0153016.
Sloan CE, Luskin MR, Boccuti AM, Sehgal AR, Zhao J, Daber RD, et al. A Modified Integrated Genetic Model for Risk Prediction in Younger Patients with Acute Myeloid Leukemia. PLoS One. 2016;11(4):e0153016.
Sloan, Caroline E., et al. “A Modified Integrated Genetic Model for Risk Prediction in Younger Patients with Acute Myeloid Leukemia.PLoS One, vol. 11, no. 4, 2016, p. e0153016. Pubmed, doi:10.1371/journal.pone.0153016.
Sloan CE, Luskin MR, Boccuti AM, Sehgal AR, Zhao J, Daber RD, Morrissette JJD, Luger SM, Bagg A, Gimotty PA, Carroll M. A Modified Integrated Genetic Model for Risk Prediction in Younger Patients with Acute Myeloid Leukemia. PLoS One. 2016;11(4):e0153016.

Published In

PLoS One

DOI

EISSN

1932-6203

Publication Date

2016

Volume

11

Issue

4

Start / End Page

e0153016

Location

United States

Related Subject Headings

  • Young Adult
  • Risk Factors
  • Retrospective Studies
  • Prognosis
  • Nucleophosmin
  • Models, Genetic
  • Middle Aged
  • Male
  • Leukemia, Myeloid, Acute
  • Humans