Allo-SCT for High-Risk AML-CR1 in the Molecular Era: Impact of FLT3/ITD Outweighs the Conventional Markers

Bone Marrow Transplant. 2012 Dec;47(12):1535-7. doi: 10.1038/bmt.2012.88. Epub 2012 Jun 4.

Abstract

Seventy-nine patients with AML in CR1 received allo-SCT between May 2006 and May 2011, and the prognostic impact of FMS-like tyrosine kinase 3/internal tandem duplication (FLT3/ITD) mutation was evaluated in the context of other clinical prognostic factors. Patients with FLT3/ITD + AML had significantly inferior DFS (2-year DFS: 19% vs 64%, P = 0.0027), increased risk of relapse (1-year: 59% vs 19%, P = 0.01), and a trend towards decreased OS (P = 0.08) compared with patients without FLT3/ITD. Multivariate analysis confirmed FLT3/ITD + independently predicted a shorter DFS (HR, 3.0; 95% CI), 1.4-6.5; P = 0.01) and increased risk of relapse (HR, 4.9; 95% CI, 2.0-12.3, P = 0.01). Time to relapse in patients with FLT3/ITD + was short with 100-day cumulative risk of 45% (95% CI, 33-57). Our data suggest that the poor prognostic implication of FLT3/ITD positivity remains even after early allo-SCT in patients with FLT3/ITD + AML, and patients remain at high risk of early relapse. FLT3/ITD positivity also outweighs other conventional prognostic markers in predicting relapse.

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use
  • Biomarkers, Tumor / genetics
  • Biomarkers, Tumor / metabolism
  • Combined Modality Therapy
  • Female
  • Humans
  • Leukemia, Myeloid, Acute / drug therapy
  • Leukemia, Myeloid, Acute / enzymology
  • Leukemia, Myeloid, Acute / genetics*
  • Leukemia, Myeloid, Acute / surgery*
  • Male
  • Middle Aged
  • Mutation
  • Prognosis
  • Stem Cell Transplantation / methods*
  • Survival Analysis
  • Tandem Repeat Sequences
  • Transplantation, Homologous
  • Treatment Outcome
  • Young Adult
  • fms-Like Tyrosine Kinase 3 / genetics*

Substances

  • Biomarkers, Tumor
  • FLT3 protein, human
  • fms-Like Tyrosine Kinase 3