ArticleCancers2022
Impact of FLT3-ITD Mutation Status and Its Ratio in a Cohort of 2901 Patients Undergoing Upfront Intensive Chemotherapy: A PETHEMA Registry Study.
Article in Cancers, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers.
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Who cites it
7 citing papers in PubMed, 9 citations in OpenAlex.
- Review
- Comparative efficacy of different therapeutic approaches in treatment naïve FLT3-mutated AML eligible for intensive chemotherapy: a Bayesian network meta-analysis of randomized trials.Annals of hematology · 2026Article
- Internal tandem duplications of FLT3 containing exogenous sequences are associated with poor clinical outcomes in acute myeloid leukemia.Annals of hematology · 2025Article
- Do NPM1 and FLT3-ITD mutations modify prognosis in patients treated with non-intensive regimens?Annals of hematology · 2024Article
- How ITD Insertion Sites Orchestrate the Biology and Disease of FLT3-ITD-Mutated Acute Myeloid Leukemia.Cancers · 2023Review
- Comparison of the 2022 and 2017 European LeukemiaNet risk classifications in a real-life cohort of the PETHEMA group.Blood cancer journal · 2023Article
- Evolving Risk Classifications in AML in a Real-Life Scenario: After Changes upon Changes, Is It More and More Adverse?Cancers · 2023Article
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Authors and funding
31 authors at 14 institutions in 1 country.
Funding
Abstract
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.
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