AML risk stratification models utilizing ELN-2017 guidelines and additional prognostic factors: A SWOG report

Era L. Pogosova-Agadjanyan, Anna Moseley, Megan Othus, Frederick R. Appelbaum, Thomas R. Chauncey, I. Ming L. Chen, Harry P. Erba, John E. Godwin, Isaac C. Jenkins, Min Fang, Mike Huynh, Kenneth J. Kopecky, Alan F. List, Jasmine Naru, Jerald P. Radich, Emily Stevens, Brooke E. Willborg, Cheryl L. Willman, Brent L. Wood, Qing ZhangSoheil Meshinchi, Derek L. Stirewalt

Research output: Contribution to journalReview articlepeer-review


Background: The recently updated European LeukemiaNet risk stratification guidelines combine cytogenetic abnormalities and genetic mutations to provide the means to triage patients with acute myeloid leukemia for optimal therapies. Despite the identification of many prognostic factors, relatively few have made their way into clinical practice. Methods: In order to assess and improve the performance of the European LeukemiaNet guidelines, we developed novel prognostic models using the biomarkers from the guidelines, age, performance status and select transcript biomarkers. The models were developed separately for mononuclear cells and viable leukemic blasts from previously untreated acute myeloid leukemia patients (discovery cohort, N = 185) who received intensive chemotherapy. Models were validated in an independent set of similarly treated patients (validation cohort, N = 166). Results: Models using European LeukemiaNet guidelines were significantly associated with clinical outcomes and, therefore, utilized as a baseline for comparisons. Models incorporating age and expression of select transcripts with biomarkers from European LeukemiaNet guidelines demonstrated higher area under the curve and C-statistics but did not show a substantial improvement in performance in the validation cohort. Subset analyses demonstrated that models using only the European LeukemiaNet guidelines were a better fit for younger patients (age < 55) than for older patients. Models integrating age and European LeukemiaNet guidelines visually showed more separation between risk groups in older patients. Models excluding results for ASXL1, CEBPA, RUNX1 and TP53, demonstrated that these mutations provide a limited overall contribution to risk stratification across the entire population, given the low frequency of mutations and confounding risk factors. Conclusions: While European LeukemiaNet guidelines remain a critical tool for triaging patients with acute myeloid leukemia, the findings illustrate the need for additional prognostic factors, including age, to improve risk stratification.

Original languageEnglish (US)
Article number29
JournalBiomarker Research
Issue number1
StatePublished - Aug 12 2020


  • AML
  • Acute myeloid leukemia
  • Biomarkers
  • ELN
  • Elderly
  • European LeukemiaNet guidelines
  • Mathematical modeling
  • Model development and validation
  • Prognostic factors

ASJC Scopus subject areas

  • Molecular Medicine
  • Clinical Biochemistry
  • Biochemistry, medical


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