The Impact of Therapy-Related Acute Myeloid Leukemia (AML) on Outcome in 2853 Adult Patients With Newly Diagnosed AML

Blood. 2011 Feb 17;117(7):2137-45. doi: 10.1182/blood-2010-08-301713. Epub 2010 Dec 2.

Abstract

To study the characteristics and clinical impact of therapy-related acute myeloid leukemia (t-AML). 200 patients (7.0%) had t-AML and 2653 de novo AML (93%). Patients with t-AML were older (P < .0001) and they had lower white blood counts (P = .003) compared with de novo AML patients; t-AML patients had abnormal cytogenetics more frequently, with overrepresentation of 11q23 translocations as well as adverse cytogenetics, including complex and monosomal karyotypes, and with underrepresentation of intermediate-risk karyotypes (P < .0001); t-AML patients had NPM1 mutations (P < .0001) and FLT3 internal tandem duplications (P = .0005) less frequently. Younger age at diagnosis of primary malignancy and treatment with intercalating agents as well as topoisomerase II inhibitors were associated with shorter latency periods to the occurrence of t-AML. In multivariable analyses, t-AML was an adverse prognostic factor for death in complete remission but not relapse in younger intensively treated patients (P < .0001 and P = .39, respectively), relapse but not death in complete remission in older, less intensively treated patients (P = .02 and P = .22, respectively) and overall survival in younger intensively treated patients (P = .01). In more intensively treated younger adults, treatment-related toxicity had a major negative impact on outcome, possibly reflecting cumulative toxicity of cancer treatment.

Publication types

  • Clinical Trial
  • Multicenter Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Age Factors
  • Aged
  • Aged, 80 and over
  • Antineoplastic Agents / adverse effects
  • Chromosome Aberrations*
  • Disease-Free Survival
  • Female
  • Humans
  • Kaplan-Meier Estimate
  • Karyotyping
  • Leukemia, Myeloid, Acute / etiology*
  • Leukemia, Myeloid, Acute / genetics*
  • Leukemia, Myeloid, Acute / mortality
  • Male
  • Middle Aged
  • Neoplasms, Radiation-Induced / etiology
  • Neoplasms, Radiation-Induced / genetics
  • Neoplasms, Radiation-Induced / mortality
  • Neoplasms, Second Primary / etiology*
  • Neoplasms, Second Primary / genetics*
  • Neoplasms, Second Primary / mortality
  • Nuclear Proteins / genetics
  • Prognosis
  • Prospective Studies
  • Risk Factors
  • Young Adult
  • fms-Like Tyrosine Kinase 3 / genetics

Substances

  • Antineoplastic Agents
  • Nuclear Proteins
  • nucleophosmin
  • FLT3 protein, human
  • fms-Like Tyrosine Kinase 3