In a groundbreaking development poised to redefine prognostic strategies in acute myeloid leukemia (AML), researchers from the Turkish AML registry project have unveiled compelling insights validating the 2022 revision of the European LeukemiaNet (ELN) guidelines, particularly emphasizing the impact of FLT3 internal tandem duplication (FLT3-ITD) mutations. These findings, soon to be published in the esteemed journal BMC Cancer, elaborate on the nuanced risk stratification critical for personalized therapeutic approaches.
The research team conducted a comprehensive retrospective analysis involving 312 newly diagnosed adult AML patients over a decade, from January 2012 to December 2022. This extensive cohort study carefully excluded cases of acute promyelocytic leukemia to maintain diagnostic specificity. Utilizing advanced polymerase chain reaction techniques complemented by next-generation sequencing when available, investigators meticulously identified FLT3-ITD mutations, a genetic aberration significantly associated with poor clinical outcomes in AML.
Central to this study is the comparative evaluation of the 2017 and 2022 ELN risk stratification models. Historically, the allelic ratio of FLT3-ITD mutations influenced classification into favorable, intermediate, or adverse risk groups. The revised 2022 ELN guidelines, however, controversially removed this allelic ratio from the risk determination framework, aiming for a biologically more coherent classification system.
Remarkably, the Turkish cohort evidenced significant reclassification of 29 patients initially categorized under favorable or adverse risk groups in the 2017 schema into the intermediate-risk category in the updated 2022 guidelines. This reallocation underscores the profound implications of revising the weightage assigned to molecular markers and highlights a progressive shift towards simplified yet effective risk categorization.
Survival analyses revealed stark contrasts aligned with these classifications. Patients stratified under the 2017 ELN favorable risk group exhibited superior overall survival (OS) — with median OS not reached — compared with intermediate-risk and adverse-risk categories, which showed median survivals of 21.6 and 9.5 months, respectively. This gradient underscores the critical prognostic value embedded within precise genetic annotation and classification.
FLT3-ITD-positive patients displayed notably inferior disease-free survival (DFS) and OS compared to their FLT3-ITD-negative counterparts. This finding reiterates the aggressive nature of FLT3-ITD mutations, reinforcing the necessity of tailored risk assessment tools to optimize treatment strategies and clinical outcomes.
Intriguingly, the intervention of allogeneic hematopoietic stem cell transplantation (HSCT) demonstrated differential benefits across risk strata. Intermediate-risk patients who achieved first complete remission (CR) experienced significant OS improvement post-HSCT, while adverse-risk patients showed only a trend towards benefit, and no significant advantage was noted for those initially classified as favorable risk. This stratified therapeutic response highlights the importance of risk-adjusted treatment decisions.
Notably, the survival outcomes of reclassified FLT3-ITD-positive patients aligned closely with those initially assigned to the intermediate-risk group under the former 2017 ELN guidelines. This alignment substantiates the rationale for the recent ELN revision, suggesting that the removal of the allelic ratio from risk stratification leads to more consistent, biologically plausible prognostic groupings.
These results hold significant clinical implications, particularly for older AML patients where tailored ELN-based risk stratification may guide therapeutic intensity and transplant candidacy more effectively. The nuanced understanding furnished by this study advocates for integrating refined molecular diagnostics with evolving risk models in AML management.
Given the modest survival benefit of HSCT observed in adverse-risk patients, the researchers emphasize the imperative for future investigations to dissect this heterogeneous group further. Additional molecular markers or combinatory risk metrics might be necessary to identify subgroups with distinct therapeutic vulnerabilities and improve their dismal prognosis.
The Turkish AML registry’s extensive data span a decade, providing a robust platform for analyzing the dynamic interplay between genetic mutations and clinical outcomes within real-world settings. Their findings exemplify the growing trend towards precision oncology, leveraging genomic insights to refine risk-adapted treatment protocols.
This study concurrently underscores the evolving landscape of AML research where continuous revision of risk stratification systems reflects a deepening understanding of disease biology. Such advancements hold promise for enhancing therapeutic efficacy and survival rates through more individualized care pathways.
As AML remains a formidable hematologic malignancy with substantial mortality, aligning clinical strategies with genetic risk signatures like FLT3-ITD mutations offers a vital route to improve patient prognoses. The 2022 ELN revision embodies this paradigm shift, solidifying its role in contemporary AML management.
In conclusion, this comprehensive Turkish AML registry analysis not only validates the prognostic utility of the 2022 ELN classification but also illuminates critical therapeutic considerations, especially in relation to FLT3-ITD mutations and HSCT efficacy. Their findings herald a new era of biologically informed risk assessment that could transform treatment algorithms and patient outcomes worldwide.
This landmark research is registered under ClinicalTrials.gov identifier NCT05979675 and reflects collaborative efforts within the Turkish Society of Hematology’s Acute Leukemias Working Group, contributing valuable data towards the global effort to combat AML.
Subject of Research: Prognostic impact of FLT3-ITD mutations in acute myeloid leukemia and validation of the 2022 European LeukemiaNet risk stratification guidelines.
Article Title: Comprehensive analysis of FLT3-mutated patients with acute myeloid leukemia with updated 2022 European LeukemiaNet recommendations: insights from the Turkish AML registry project.
Article References:
Pinar, I.E., Celik, S., Polat, M.G. et al. Comprehensive analysis of FLT3-mutated patients with acute myeloid leukemia with updated 2022 European LeukemiaNet recommendations: insights from the Turkish AML registry project. BMC Cancer 25, 1546 (2025). https://doi.org/10.1186/s12885-025-14987-z
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