Mutation topography and risk stratification for de novo acute myeloid leukaemia with normal cytogenetics and no nucleophosmin 1 (NPM1) mutation or Fms-like tyrosine kinase 3 internal tandem duplication (FLT3-ITD).

About 25% of patients with newly diagnosed acute myeloid leukaemia (AML) have normal cytogenetics and no nucleophosmin 1 (NPM1) mutation or Fms-like tyrosine kinase 3 internal tandem duplication (FLT3-ITD). The prognosis and best therapy for these patients is controversial. We evaluated 158 newly diagnosed adults with this genotype who achieved histological complete remission within two cycles of induction therapy and were assigned to two post-remission strategies with and without an allotransplant. Targeted regional sequencing at diagnosis was performed and data were used to estimate their prognosis, including relapse and survival. In multivariable analyses, having wild-type or mono-allelic mutated CCAAT/enhancer-binding protein alpha (CEBPA) [hazard ratio (HR) 2 center dot 39, 95% confidence interval (CI) 1 center dot 08-5 center dot 30; P = 0 center dot 032), mutated NRAS (HR 2 center dot 67, 95% CI 1 center dot 36-5 center dot 25; P = 0 center dot 004), mutated colony-stimulating factor 3 receptor (CSF3R) (HR 2 center dot 85, 95% CI 1 center dot 12-7 center dot 27; P = 0 center dot 028) and a positive measurable residual disease (MRD)-test after the second consolidation cycle (HR 2 center dot 88, 95% CI 1 center dot 32-6 center dot 30; P = 0 center dot 008) were independently correlated with higher cumulative incidence of relapse (CIR). These variables were also significantly associated with worse survival (HR 3 center dot 02, 95% CI 1 center dot 17-7 center dot 78, P = 0 center dot 022; HR 3 center dot 62, 95% CI 1 center dot 51-8 center dot 68, P = 0 center dot 004; HR 3 center dot 14, 95% CI 1 center dot 06-9 center dot 31, P = 0 center dot 039; HR 4 center dot 03, 95% CI 1 center dot 64-9 center dot 89, P = 0 center dot 002; respectively). Patients with >= 1 of these adverse-risk variables benefitted from a transplant, whereas the others did not. In conclusion, we identified variables associated with CIR and survival in patients with AML and normal cytogenetics without a NPM1 mutation or FLT3-ITD.