Prognostic significance of FLT3 internal tandem duplication and tyrosine kinase domain mutations for acute myeloid leukemia: a meta-analysis

Two distinct forms of fms-like tyrosine kinase (FLT3) gene aberrations, internal tandem duplication (ITD) and tyrosine kinase domain (TKD) mutations, have been recognized in a substantial proportion of patients with acute myeloid leukemia (AML). To investigate their prognostic significance, we performed a meta-analysis of the four published studies that provided survival information according to the FLT3 status: ITD, TKD mutation, and wild type. The summary hazard ratios for disease-free survival (DFS) were 1.88 ( 95% confidence interval (CI) 1.58- 2.23; P < 0.001) for FLT3 mutations, 1.86 (95% CI: 1.52-2.29; P < 0.001) for ITD, and 1.90 (95% CI: 1.40-2.60; P < 0.001) for TKD mutation. The corresponding ratios for overall survival were 1.61 (95% CI: 1.37-1.89; P < 0.001), 1.68 (95% CI: 1.39-2.03; P < 0.001), and 1.37 (95% CI: 0.94-2.01; P=0.104). Neither white blood cell count at diagnosis nor cytogenetic risk category was a significant source of heterogeneity. These findings indicate that FLT3 mutations have an adverse effect on the outcome for AML, and that the negative impact of TKD mutation seems comparable to that of ITD with regard to DFS. Although it should be borne in mind that this meta-analysis was based on data abstracted from observational studies, these results may justify the risk-adapted therapeutic strategies for AML according to the FLT3 status.