SURVIVAL ASSESSMENT IN AML PATIENTS WITH FLT3 MUTATION TREATED AT A REFERRAL HOSPITAL IN THE AMAZONAS STATE, BRAZIL

Abstract

Introduction: Acute Myeloid Leukemia (AML) is a malignant clonal hematological, marked by clonal proliferation neoplasm cells of the myeloid lineage in the bone marrow, characterized by presence of different genetic alterations. Variants in the FLT3 gene (FMS-like tyrosine kinase 3) are related with development of the disease, FLT3 mutation is present in 10-35% of the AML cases. FLT3 variants influence in the origin of aggressive and resistant clones related worse survival outcome when not treated adequately. Objective: To evaluate the clinical profile and survival of the AML patients accord FLT3 status and cytogenetics features in the Hematology and Hemotherapy Foundation of the Amazonas State (HEMOAM). Materials and methods: Was performed prospective study with AML patients over 18 years old, proceeding Amazonas state, treated between January/2022 to October/2023 in the HEMOAM. The cytogenetic analysis was performed by G band and FLT3 variants screening in the 8-24 exons by nucleotide sequencing. Survival analysis was by Kaplan-Meirer, and Log-rank test, the median follow-up was 400 days. Results: A total of 29 AML patients were included with median 42 years (28-69 years), being 17 (59%) female patients. Chromosomal alteration was prevalent in 19 (66%) of the AML patients, 4 (14%) classified as favorable risk, 21 (72%) intermediary and 4 (14%) as adverse risk. Different FLT3 variants were identified, FLT3-ITD present in 5 (17.3%) patients and missense variants in 7 (24.1%) of the cases. From patients evaluated, 17 (59%) died and 12 (41%) survived until the end of the research, with a median survival of 150 days. Although, patients with missense variants present shorter survival time (110 days) when compared with FLT3 negative and FLT3-ITD+, 439 and 142.5 days, respectively. That patients classified as intermediary risk presented shorter survival time (110 days) when compared with favorable and adverse. Discussion: Here, female patients and young subjects were most prevalent in the study population, different features when compared to global data. The mortality rate was elevated (59%). FLT3 variants are frequently observed in AML patients, which in this study the missense variants were more prevalent (24.1%). FLT3 mutation and cytogenetic changes contribute to risk stratification and treatment direction. That patients carrier some FLT3 variant present lower survival time, as observed to missense variants. Conclusion: Despite the low sample size, our data suggests a possible trend of the FLT3 status with unfavorable clinical outcome, highlighting the missense variants and genomic alterations.