In the following case, we demonstrate, for the first time to our knowledge, polyspecific cytotoxic T-cell (CTL) responses against several known leukemia-associated antigens (LAAs) in a patient with acute myeloid leukemia (AML) with NPM1 mutation (NPM1mut) after preemptive donor lymphocyte infusion (DLI) in molecular relapse. Importantly, immune responses against LAAs were associated with minimal residual disease (MRD) negativity. Delayed DLI already plays a key role in supporting the graftversus-leukemia (GvL) effect after allogeneic hematopoietic stem-cell transplantation (HSCT), although the potency of DLI differs for each disease entity. The GvL effect observed after DLI is based on CTL-mediated immunity, which is reactive against minor histocompatibility antigens as well as LAAs. However, DLI carries the risk of morbidity and mortality as a result of graft-versus-host disease (GvHD). The role of LAAs in GvL has yet to be elucidated. After a written informed consent was completed in accordance with the Declaration of Helsinki, we analyzed the peripheral blood (PB) of a 57-year-old woman with AML with NPM1mut. The patient developed molecular relapse without detectable myeloid blasts in PB and bone marrow (BM) at day 171 after allogeneic HSCT and received preemptive DLI at day 260. Blood samples were taken before and after DLI and investigated for specific T-cell reactivity against several LAAs for which CTL responses were already described. In addition, immune status was determined by measuring the counts of subsets of T-and B-cells at several time points (Fig 1). To test specific CTL responses, interferon-gamma enzyme-linked immunosorbent spot analysis and tetramer assays were performed.