Impact of Chemotherapy Delay on Overall Survival for AML with IDH1/2 Mutations: A Study in Adult Chinese Patients

PLoS One. 2015 Oct 14;10(10):e0140622. doi: 10.1371/journal.pone.0140622. eCollection 2015.

Abstract

The effect of time from diagnosis to treatment (TDT) on overall survival of patients with acute myeloid leukemia (AML) remains obscure. Furthermore, whether chemotherapy delay impacts overall survival (OS) of patients with a special molecular subtype has not been investigated. Here, we enrolled 364 cases of AML to assess the effect of TDT on OS by fractional polynomial regression in the context of clinical parameters and genes of FLT3ITD, NPM1, CEBPA, DNMT3a, and IDH1/2 mutations. Results of the current study show IDH1/2 mutations are associated with older age, M0 morphology, an intermediate cytogenetic risk group, and NPM1 mutations. TDT associates with OS for AML patients in a nonlinear pattern with a J shape. Moreover, adverse effect of delayed treatment on OS was observed in patients with IDH1/2 mutations, but not in those with IDH1/2 wildtype. Therefore, initiating chemotherapy as soon as possible after diagnosis might be a potential strategy to improve OS in AML patients with IDH1/2 mutations.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Aged, 80 and over
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Asian People
  • China
  • Female
  • Humans
  • Isocitrate Dehydrogenase / genetics*
  • Leukemia, Myeloid, Acute / diagnosis
  • Leukemia, Myeloid, Acute / drug therapy*
  • Leukemia, Myeloid, Acute / genetics*
  • Leukemia, Myeloid, Acute / mortality
  • Male
  • Middle Aged
  • Mutation*
  • Nucleophosmin
  • Prognosis
  • Time Factors
  • Young Adult

Substances

  • NPM1 protein, human
  • Nucleophosmin
  • IDH2 protein, human
  • Isocitrate Dehydrogenase
  • IDH1 protein, human

Grants and funding

This work was supported by National Natural Science Foundation of China grants (81470305), National Public Health Grant Research Foundation (201202017) and the Foundation of Innovation Team for Basic and Clinical Research of Zhejiang Province (2011R50015). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.