FLT3 internal tandem duplication does not impact prognosis after haploidentical allogeneic hematopoietic stem cell transplantation in AML patients

Bone Marrow Transplant. 2019 Sep;54(9):1462-1470. doi: 10.1038/s41409-019-0456-x. Epub 2019 Feb 1.

Abstract

Acute myelogenous leukemia (AML) patients with fetal liver tyrosine kinase 3 (FLT3) internal tandem duplications (ITDs) have poor prognoses if treated with chemotherapy only, primarily as they experience increased relapse rates. To determine whether this alteration also affects outcomes after haploidentical donor (HID) allogeneic hematopoietic stem cell transplantation (allo-HSCT), we compared 334 consecutive FLT3-ITD-positive vs -negative patients with AML (other than acute promyelocytic leukemia) who underwent HID-HSCT. FLT3-ITD was detected in 39 of 334 patients (11.7%). The 2-year relapse rates for FLT3-ITD-positive and -negative patients were 16% and 17%, respectively (P = 0.774). The 3-year disease-free survival (DFS) rates for FLT3-ITD-positive and -negative patients were 74% (95% confidence interval [CI]: 64-81) and 73% (95% CI: 70-81), respectively; P = 0.872); while the 3-year overall survival (OS) rates were 72% (95% CI: 67-81) and 77% (95% CI: 72-84), respectively (P = 0.862). FLT3-ITD mutation had no influence on non-relapse mortality (NRM 15% vs 14%, P = 0.463). Multivariate analyses showed that disease status at HSCT and white blood cell count at diagnosis were independent risk factors associated with relapse, DFS, and OS. In conclusion, FLT3 mutation status has no impact on outcomes after HID-HSCT in patients with AML. HID-HSCT is therefore a valid option for AML patients with FLT3-ITD mutation.

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Allografts
  • Child
  • Child, Preschool
  • Disease-Free Survival
  • Female
  • Follow-Up Studies
  • Hematopoietic Stem Cell Transplantation*
  • Humans
  • Leukemia, Promyelocytic, Acute* / diagnosis
  • Leukemia, Promyelocytic, Acute* / genetics
  • Leukemia, Promyelocytic, Acute* / mortality
  • Leukemia, Promyelocytic, Acute* / therapy
  • Male
  • Middle Aged
  • Mutation*
  • Survival Rate
  • fms-Like Tyrosine Kinase 3 / genetics*

Substances

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