P100 | CRUCIAL ROLE OF NEXT GENERATION SEQUENCING IN THE PROGNOSTIC RECLASSIFICATION OF INTERMEDIATE-RISK ACUTE MYELOID LEUKEMIAS: THE SIENA HEMATOLOGY EXPERIENCE

AML risk classification based on genetic aberrations plays a pivotal role in predicting prognosis and guiding treatment choices. In 2022, the European LeukemiaNet (ELN) issued updated recommendations for diagnosis and risk classification, building upon the ELN2017 guidelines. It has been necessary to evaluate the possibility to change some therapeutic decisions particularly for AML patients (pts) classified in the intermediate-risk according to ELN2017 eligible for allogeneic transplantation. NGS have become the gold standard for detection of additional somatic variants in AML pts and for a better risk classification. The aim of this study was to reclassify AML pts previously classified as intermediate-risk according to ELN2017 guidelines, through the search for additional myeloid mutations by NGS. We conducted a comparison between the 2017 and 2022 ELN risk classifications in a real-world monocentric cohort of de novo or secondary AML pts diagnosed from January 2019 to January 2024. An NGS myeloid panel was employed in samples at diagnosis to identify genetic variants with a variant allele frequency (VAF) ≥ 5%.27 AML pts were evaluated, with a median age at diagnosis of 65 years (28-75 yrs). Genetic mutations identified by NGS allowed us to reclassify 9/27 (33.3%) pts who became high-risk for ELN2022 while 18/27 (66.7%) remained in the intermediate-risk category. The most frequent mutations identified, in addition to NPM1 and FLT3, were DNMT3A in 33.3% pts (9/27), SRSF2 in 22.2% pts (6/27) and IDH1 in 18.5% pts (5/27). Comparing the 2 groups, 72.2% of intermediate-risk pts had newly diagnosed AML, 27.8% had secondary AML, and 55.6% of high-risk pts had secondary AML. The survival of the 2 groups was not significantly different (p=0.35): overall survival (OS) at 12 months was 71.1% in the intermediate-risk group and 88.9% in the high-risk group (Figure 1). Comparing the OS according to the transplantation, all intermediate- and high-risk pts who received a cell transplantation had a 12-month OS of 100%. Data obtained from NGS analysis contributed to demonstrate that pts previously classified in the intermediate-risk, resulted with a high-risk of disease; however, our unaware decision to candidate intermediate-risk AML pts for allogeneic transplantation, represented an optimal therapeutic strategy. The use of the NSG has proven crucial, allowing clinicians to evaluate increasingly personalized and effective therapeutic approaches in the treatment of AML.