Importance of prognostic stratification via gene mutation analysis in elderly patients with acute myelogenous leukemia

Int J Lab Hematol. 2019 Aug;41(4):461-471. doi: 10.1111/ijlh.13025. Epub 2019 Apr 10.

Abstract

Introduction: Acute myelogenous leukemia (AML) in elderly patients is associated with an increased incidence of complications and treatment-related toxicity because of the frequency of comorbid disease and age-related deterioration in organ function. Despite advances in AML treatment in recent years, elderly patients have experienced limited benefit, and their outcomes remain poor. This study aimed to perform a comprehensive gene mutation analysis in elderly AML patients and identify gene mutations that could serve as prognostic factors.

Methods: An analysis of gene mutations was performed for 281 AML patients, including 98 elderly patients aged 65 years or above.

Results: Compared to younger AML patients, elderly patients showed a higher frequency of the following gene mutations: TP53 (P = 0.026), PTPN11 (P = 0.006), RUNX1 (P = 0.024), TET2 (P = 0.002), and ASXL1 (P = 0.023). The complete remission rate was significantly lower in DNMT3A mutation-positive cases (4.26%, P = 0.011) and TP53 mutation-positive cases (2.13%, P = 0.031) than in negative cases. The overall survival rate was significantly poorer in cases with FLT3-ITD (P = 0.003), DNMT3A (P = 0.033), or TP53 mutation (P < 0.001). Conversely, cases with PTPN11 mutation (P = 0.014) had a significantly more favorable prognosis. In multivariate analysis, FLT3-ITD (P = 0.011) and TP53 mutation positivity (P = 0.002) were independent poor prognostic factors, as were a performance status of 3 or above (P < 0.001) and poor cytogenetic prognosis (P = 0.001). In contrast, PTPN11 mutation positivity (P = 0.023) was an independent favorable prognosis factor.

Conclusion: Analysis of gene mutations in elderly AML patients is very important, not only for establishing prognosis, but also for introducing appropriate molecular-targeted treatments.

Keywords: acute myeloid leukemia; elderly; gene mutation; prognostic factor; remission rate.

Publication types

  • Clinical Trial

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Aged, 80 and over
  • Disease-Free Survival
  • Female
  • Humans
  • Leukemia, Myeloid, Acute / genetics*
  • Leukemia, Myeloid, Acute / mortality*
  • Male
  • Middle Aged
  • Mutation*
  • Neoplasm Proteins / genetics*
  • Remission Induction
  • Survival Rate

Substances

  • Neoplasm Proteins