Clinical characteristics and outcomes of extramedullary acute myeloid leukemia: a 20-year referral center experience

Abstract Extramedullary disease (EMD) in acute myeloid leukemia (AML) is a heterogeneous entity, and distinctions between systemic EMD and central nervous system (CNS) leukemia remain poorly understood. We conducted a single-center retrospective study of clinical characteristics, mutational profiles, treatment responses, and survival outcomes in 52 adults with EMD (31 with systemic EMD and 21 with CNS leukemia) treated at the University of Iowa Health Care between 2006 and 2025. Frequencies of NPM1, FLT3, and RAS pathway gene mutations were similar between systemic EMD and CNS leukemia cohorts. Complete remission (CR) rates after induction were comparable between patients with systemic EMD (66.7%) and those with CNS leukemia (61.9%). Among the 22 patients with systemic EMD who achieved bone marrow CR, 10 (45.5%) were minimal residual disease (MRD)-positive and 12 (54.5%) were MRD-negative. Among the 13 patients with CNS leukemia who achieved CR, 5 (38.5%) were MRD-positive and 8 (61.5%) were MRD-negative. In CNS leukemia, European LeukemiaNet 2022 adverse-risk disease was associated with more intrathecal chemotherapy treatments required for CNS clearance (β = 1.83, p = 0.03). Median overall survival was 28.3 months (95% confidence interval [CI], 12.1-not reached) for systemic EMD and 17.2 months (95% CI, 9.3–27.9) for CNS leukemia.