Extramedullary AML: Clinical and Molecular Features

Background: Acute myeloid leukemia with extramedullary disease (EMD-AML) represents a distinct clinical entity associated with diagnostic and therapeutic challenges, and its prognostic significance remains uncertain. Methods: A retrospective study of 617 adults with newly diagnosed AML (2005–2018) was conducted, analyzing 246 patients with EMD-AML and 371 without EMD involvement. The clinical characteristics and treatment outcomes were analyzed. Propensity score matching (PSM) was applied to adjust for baseline confounders. Results: Patients with isolated EMD-AML and those with concurrent bone marrow involvement had comparable clinical outcomes. NPM1 mutations (48% vs. 25%, p = 0.0002) and t(8;21) translocation (23.2% vs. 3.7%, p < 0.001) were enriched in the EMD-AML cohort. After PSM, EMD-AML patients achieved a higher overall response rate compared with non-EMD-AML (88.1% vs. 72.0%, p = 0.0002) but experienced significantly higher relapse rates (35.7% vs. 15.5%, p < 0.0001). Despite the achievement of a higher response rate, EMD-AML was associated with shorter median overall survival (OS) (14.2 vs. 64.1 months, p < 0.0001) and event-free survival (EFS) (9.5 vs. 55.9 months, p < 0.0001). In a multivariable analysis, EMD-AML remained independently associated with worse OS and EFS (OS HR 1.79, p = 0.01; EFS HR 1.95, p = 0.001). Allogeneic hematopoietic stem cell transplantation did not confer a survival advantage in EMD-AML patients. Conclusions: EMD-AML, whether isolated or concurrent with bone marrow disease, represents a high-risk entity characterized by poor long-term outcomes despite strong initial response rates. Obtaining tissue biopsies for molecular profiling may help improve risk stratification, identify targetable mutations and guide individualized treatment.