DP082 | IMPACT OF FLT3-ITD LENGTH ON OUTCOME IN ACUTE MYELOID LEUKEMIA PATIENTS

Acute Myeloid Leukemia (AML) is a malignant and heterogeneous disease of hematopoietic system, characterized by recurrent genetic and chromosomal abnormalities. A common mutation is on FLT3 gene, that encodes a receptor tyrosine-kinase, involved in hematopoietic development. FLT3 mutations include (i) FLT3-Internal Tandem Duplication (FLT3-ITD), found in 20-25% of cases, and (ii) FLT3-Tirosine Kinase Domain (FLT3-TKD), found in 7-10%. ITD size can vary significantly from 3 to hundreds of nucleotides located in the juxta membrane domain in approximately 70% of the cases and TKD1 in the remaining 30%. The impact of ITD length on clinical outcomes remains debated, with contradictory findings in the literature. This single-Centre observational study includes adult patients diagnosed with de novo or secondary AML carrying an FLT3-ITD mutation, detected by NGS or RT-qPCR, and referred to Brescia Hospital between 2019 and 2025. The study aims to investigate the unclear relationship between ITD length and clinical outcomes. Seventy patients (pts) were evaluated, with a median age of 65.5 years (IQR 53.75 – 73). A significant proportion of pts (32/70, 46%) presented AML with defining genetic abnormalities according to the latest WHO classification. Based on ELN risk stratification, 45 pts (64%) were classified as intermediate risk, 20 pts (29%) as high risk, while risk was unknown in 5 cases (7%). The median ITD mutation length is 48 base pair (IQR 30 – 66.75). The proportion of patients with an ITD length below the 1st quartile is 21 (30%), between the 1st and 3rd 30 (43%), and above the 3rd 19 (27%). There are very interesting results related to Overall Survival (OS): the OS at one year after diagnosis is affected by ITD length, with significant differences between pts below the 1st and pts above the 3rd quartiles (p = 0.02). However, long-term OS (at 3 years), is not affected by length (Fig. 1). Also, relapse incidence is strongly associated with ITD length, showing significant differences comparing pts below 1st vs pt above the 3rd quartiles (p = 0.0001) and between 1st and 3rd vs above the 3rd quartile (p = 0.0045). In conclusion, this analysis suggests that FLT3-ITD length influences short-term survival but not long-term outcomes, with a higher relapse incidence observed in patients carrying an ITD longer than 67 bp. These findings underscore the potential prognostic significance of ITD size, supporting the need for further validation in larger patient cohorts.