Predictive value of natural killer (NK) cells in bone marrow for relapse in diffuse large B cell lymphoma: integrating antibody-dependent cell-mediated cytotoxicity (ADCC)-based immunotherapy

PURPOSE: Diffuse large B cell lymphoma (DLBCL) is characterized by high relapse rates and immunobiological complexity. The therapeutic efficacy of CD20-targeting monoclonal antibodies depends largely on antibody-dependent cellular cytotoxicity (ADCC), mediated by natural killer (NK) cells. METHODS: We evaluated the percentage of bone marrow NK cells in 47 newly diagnosed DLBCL patients by flow cytometry prior to first-line chemoimmunotherapy. ADCC potential was assessed using immunological parameters. RESULTS: Patients with ≥ 14% bone marrow NK cells had significantly better event-free survival (EFS), with median EFS nearly doubled compared with those below this threshold (HR = 0.24, p < 0.05). Logistic regression predicted a 77% probability of remaining relapse-free at NK percentages > 14%. In multivariable Cox regression, bone marrow NK percentage remained independently predictive of EFS after adjustment for International Prognostic Index (IPI), age, and treatment regimen. Although overall survival did not differ significantly, higher NK levels were associated with improved clinical response. CONCLUSION: Patients with higher NK cell percentages may better tolerate chemotherapy-induced depletion, thereby preserving or restoring their effector pool more efficiently. Elevated bone marrow NK cell percentages predict favorable outcomes in DLBCL and support their potential role as translational biomarkers. Incorporating NK cell monitoring into clinical protocols could improve risk stratification and guide immunotherapeutic strategies for personalized patient management.