Long-term results of a prospective randomized trial evaluating G-CSF priming in intensive induction chemotherapy followed by autologous stem cell transplantation in elderly patients with acute myeloid leukemia

Ann Hematol. 2014 Feb;93(2):193-202. doi: 10.1007/s00277-013-1873-3. Epub 2013 Aug 27.

Abstract

Few studies have evaluated granulocyte colony-stimulating factor (G-CSF) priming in elderly patients with intensively treated acute myeloid leukemia (AML), and no data are available for genetically defined AML subgroups. We provide long-term results (median follow-up 7.6 years) of a randomized trial in which 183 patients (median age 67 years) received G-CSF prior to (G-CSF priming) or after two cycles of induction chemotherapy. CR rates with G-CSF priming and G-CSF post-chemotherapy were comparable (57 vs. 67 %, p = 0.153), with overall survival (OS) probabilities of 14 vs. 17 % at 10 years. Induction mortality was significantly higher with G-CSF priming (23 vs. 10 %, p = 0.015), primarily in normal karyotype (NK) AML. In this subgroup, a trend for better relapse-free survival (RFS) was observed with G-CSF priming (44 vs. 22 % at 10 years, p = 0.074) but did not translate into an OS benefit. G-CSF priming had no impact on AML with FLT3-ITD and NPM mutations and did not improve outcome in patients with adverse cytogenetics. In a landmark analysis, late consolidation with autologous stem cell transplantation or a second consolidation cycle significantly improved RFS compared with one consolidation cycle (21.0 vs. 12.8 months, p = 0.046). Future studies on G-CSF priming should be restricted to NK AML and used only in post-remission therapy.

Publication types

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

MeSH terms

  • Aged
  • Aged, 80 and over
  • Autografts
  • Disease-Free Survival
  • Female
  • Follow-Up Studies
  • Granulocyte Colony-Stimulating Factor / administration & dosage
  • Granulocyte Colony-Stimulating Factor / adverse effects*
  • Hematopoietic Stem Cell Transplantation*
  • Humans
  • Induction Chemotherapy / adverse effects*
  • Leukemia, Myeloid, Acute / genetics
  • Leukemia, Myeloid, Acute / mortality*
  • Leukemia, Myeloid, Acute / pathology
  • Leukemia, Myeloid, Acute / therapy*
  • Male
  • Middle Aged
  • Mutation
  • Prospective Studies
  • Survival Rate
  • Time Factors
  • fms-Like Tyrosine Kinase 3 / genetics

Substances

  • Granulocyte Colony-Stimulating Factor
  • FLT3 protein, human
  • fms-Like Tyrosine Kinase 3