Acute Myeloid Leukemia (AML) is a prevalent and severe hematological disorder. Emergence of Next-Generation Sequencing (NGS) and karyotiping, has demonstrated associations between chromosomal abnormalities and mutations with worse treatment response and mortality in AML. Despite its evident importance in AML, application of these diagnostic methods poses new challenges. In Latin America, particularly, there is a clear limitation of data and studies regarding molecular and cytogenetic analysis in AML patients.

Provide an in-depth evaluation of the application of NGS and cytogenetic analysis in AML, identifying the impact of somatic mutations on AML morbimortality based on the experience of a reference center in Latin America.

This is a retrospective, non-interventional cohort performed in Brazilian Hospital Albert Einstein. Inclusion criteria were adult patients diagnosed with AML between May 2017 and August 2022, who underwent myeloid panel testing through NGS and cytogenetic evaluation at diagnosis. Independent variables analyzed were age, gender, ELN 2022 prognostic risk, indication of bone marrow transplantation and molecular and cytogenetic risk at diagnosis. High cytogenetic risk was defined by the presence of at least one of the high-risk karyotype abnormalities described in ELN 2022 and high-risk NGS was defined by mutated ASXL1, BCOR, EZH2, RUNX1, SF3B1, SRSF2, U2AF1, ZRSR2, TP53 or FLT3. The primary outcomes evaluated were overall survival (OS) and progression-free-survival (PFS). Secondary outcomes were disease relapse and non-relapse-related mortality (NRM).

64 patients were included in the study with a mean age of 62,7 years. 42 (65,6%) patients presented standard-risk karyotype, whereas high-risk karyotype was found in 22 (34,4%) patients. 73,4% individuals presented high-risk NGS mutations, with higher prevalence of rearrangements in RUNX1 (20,1%), FLT3 (18,7%) and TP53 (15,6%). After a median follow-up of 26 months, estimated OS was 73% in 1 year and 54% in 2 years. 1 and 2 years PFS was 63% and 45%, respectively. 11% relapsed after 1 year and 27% after 2 years. NRM was 25% and 28% after 1 and 2 years, respectively. High-risk karyotype was associated with a signficant reduction in overall survival (hazard ratio [HR] 2,27, 95% CI 1,09–4,70; p = 0,028) and progression-free-survival (HR 2,15, CI 1,23–4,11). There was no significant association between high molecular risk by NGS and OS (HR 1.45, 0.59-3.58) or PFS (HR 1.43, CI 0.65-3.13). Progressive age has discreetly impacted in OS (HR 1,05, CI 1,02-1,08), PFS (HR 1,03CI 1-1,05) and NRM (HR 1,06, CI 1,02-1,11; p = 0,002). No differences in outcomes were found between sex, ELN 2022 risk groups, and treatment with bone marrow transplantation.

NGS and cytogenetic analysis have improved precision in prognosis prediction of AML patients of each patient, allowing safe implementation of appropriate individualized therapy. This study showed association between high-risk cytogenetics and worse prognosis in AML, but no association was observed between molecular risk and AML morbimortality. Further studies with a bigger population and longer follow-up should be conducted in order to better clarify and delve deeper into the results reported in this cohort.