Prognostic impact of combined NPM1+/FLT3− genotype in patients with acute myeloid leukemia with intermediate risk cytogenetics stratified by age and treatment modalities

The prognostic impact of combined NPM1+/FLT3− genotype is not well defined in elderly patients with acute myeloid leukemia (AML), and in the setting of different treatments, such as cytotoxic chemotherapy (Chemo), hematopoietic cell transplantation (HCT), or hypomethylating agents (HMA). Eighty-two elderly (age >60 years) and 78 younger adults (age 18-60 years) with newly diagnosed intermediate-risk cytogenetic AML were classified according to the presence or absence of NPM1+/FLT3− genotype, and treatments (Chemo vs. HCT. vs. HMA). The estimated 3-year overall survivals (OS) in elderly (N = 17) and younger adults (N = 13) with NPM1+/FLT3− treated with Chemo were 59% and 64%, respectively (P = 0.71). In the absence of NPM1+/FLT3−, younger adults had a superior OS when treated with HCT than with Chemo (P < 0.0001), but elderly showed no survival advantage with HCT after adjustment for baseline covariates. Elderly patients lacking NPM1+/FLT3− had a comparable OS when treated with Chemo vs. HMA (P = 0.79). Combined NPM1+/FLT3− is associated with a favorable prognosis irrespective of age in AML patients treated with Chemo. In the absence of NPM1+/FLT3− genotype, younger adults undergoing HCT have an improved survival, while elderly have comparable OS when treated with Chemo vs. HMA.