The incidence and prognostic effect of Fms-like tyrosine kinase 3 gene internal tandem and nucleolar phosphoprotein 1 genes in acute myeloid leukaemia: A PRISMA-compliant systematic review and meta-analysis

Background:Molecular genotyping is an important prognostic role in acute myeloid leukemia (AML) patients. We aimed to design this meta-analysis to discuss the incidence and prognostic effect of nucleolar phosphoprotein 1 (NPM1) and Fms-like tyrosine kinase 3 gene internal tandem (FLT3-ITD) gene in AML patients.Methods:PubMed, Embase, Medline, and Cochrane library were systematically searched due to May 15, 2020. Four combinations of genotypes (FLT3-ITD^neg/NPM1^mut, FLT3-ITD^pos/NPM1^mut, FLT3-ITD^neg/NPM1^wt, FLT3-ITD^pos/NPM1^wt) were compared in association with the overall survival (OS) and leukemia-free survival (LFS) outcome, which expressed as pooled hazard ratio (HR) and 95% confidence intervals (CIs).Results:Twenty-eight studies were included in our study. The incidence of FLT3-ITD^neg/NPM1^mut, FLT3-ITD^pos/NPM1^mut, FLT3-ITD^neg/NPM1^wt, and FLT3-ITD^pos/NPM1^wt was 16%, 13%, 50%, and 10%, respectively. The patients with FLT3-ITD^neg/NPM1^mut gene may have the best OS and LFS when comparing with FLT3-ITD^pos/NPM1^mut (HR = 1.94 and 1.70, P < .01), FLT3-ITD^neg/NPM1^wt (HR = 1.57 and 2.09, P < .01), and FLT3-ITD^pos/NPM1^wt (HR = 2.25 and 2.84, P < .001).Conclusion:AML patients with FLT3-ITD^neg/NPM1^mut gene type have the best survival outcome than the other 3 gene types, which should be an independent genotyping in AML classification.