Monitoring of (Potentially Leukemia-Specific) Immune Cells After AML Relapse Post-Transplantation Across Treatment Groups and Disease Stages

Purpose: Relapse after allogeneic stem cell transplantation (SCT) in acute myeloid leukemia (AML) remains a major therapeutic challenge. This study longitudinally assessed immune responses in relapsed AML patients post-SCT under different therapeutic regimens, focusing on (potentially) leukemia-specific cytotoxicity and survival outcomes. Methods: The composition and profile of peripheral immune cells of 14 AML patients in hematological relapse post-SCT were evaluated by flow cytometry. Patients were stratified by clinical stage and treatment: relapse without therapy (Rw/o), relapse under/after HMA ± VCLX (RHMAs/VCLX), relapse under/after Kit-M treatment (RKit-M), and complete or partial remission after treatment (PR/CR). Frequencies of blasts, dendritic cells, (potentially) leukemia-specific IFNγ-producing or CD107a-degranulating T/NK/CIK cells, and immune checkpoint marker expression (PD-1, CTLA-4, TIM-3, TIGIT, KLRG1) were quantified. Immune profiles were also compared between long-term survivors (‘alive’) and ‘deceased’ patients. Results: Increased immune activation, characterized by increased frequencies of (potentially) leukemia-derived dendritic cells, enhanced frequencies of CD107a+/IFNγ+ effector and memory T/NK cells and reduced frequencies of cells expressing inhibitory checkpoint markers observed in the RHMAs/VCLX group (and even more in a single anecdotal patient, treated with Kit M RKit-M). Patients in remission after treatment (PR/CR) exhibited stabilization of these immune effects, indicating restored immune surveillance. Long-term survivors exhibited higher frequencies of functional CD107a+ T and IFNγ+ NK/CIK cells, while the ‘deceased’ group displayed signs of increased immune exhaustion and diminished effector responses. Conclusions: HMA/VCLX therapy (and Kit-M treatment) induced measurable, potentially) (leukemia-specific) immune responses in relapsed AML patients post-SCT. Elevated functional immune subsets correlated with long-term survival, underscoring their role as potential prognostic biomarkers. Despite a very heterogeneous patient cohort and treatment, our findings support immune monitoring post-SCT to improve risk stratification and highlight the therapeutic potential of immune-modulating treatments in relapsed AML.