FLT3–ITD results in a poor prognosis in terms of overall survival (OS) and relapse-free
survival (RFS) in acute myeloid leukemia (AML). However, the prognostic usefulness of the allelic
ratio (AR) to select post-remission therapy remains controversial. Our study focuses on the prognostic
impact of FLT3–ITD and its ratio in a series of 2901 adult patients treated intensively in the pre-FLT3
inhibitor era and reported in the PETHEMA registry. A total of 579 of these patients (20%) harbored FLT3–ITD mutations. In multivariate analyses, patients with an FLT3–ITD allele ratio (AR) of >0.5
showed a lower complete remission (CR rate) and OS (HR 1.47, p = 0.009), while AR > 0.8 was
associated with poorer RFS (HR 2.1; p < 0.001). Among NPM1/FLT3–ITD-mutated patients, median
OS gradually decreased according to FLT3–ITD status and ratio (34.3 months FLT3–ITD-negative,
25.3 months up to 0.25, 14.5 months up to 0.5, and 10 months ≥ 0.5, p < 0.001). Post-remission
allogeneic transplant (allo-HSCT) resulted in better OS and RFS as compared to auto-HSCT in
NPM1/FLT3–ITD-mutated AML regardless of pre-established AR cutoff (≤0.5 vs. >0.5). Using the
maximally selected log-rank statistics, we established an optimal cutoff of FLT3–ITD AR of 0.44
for OS, and 0.8 for RFS. We analyzed the OS and RFS according to FLT3–ITD status in all patients,
and we found that the group of FLT3–ITD-positive patients with AR < 0.44 had similar 5-year OS
after allo-HSCT or auto-HSCT (52% and 41%, respectively, p = 0.86), but worse RFS after auto-HSCT
(p = 0.01). Among patients with FLT3–ITD AR > 0.44, allo-HSCT was superior to auto-HSCT in terms
of OS and RFS. This study provides more evidence for a better characterization of patients with AML
harboring FLT3–ITD mutations