Evaluating the safety and feasibility of prophylactic third-party NK cell administration in high-risk AML patients post-HSCT.

BACKGROUND: Relapse is a major cause of treatment failure in high-risk acute myeloid leukemia (AML) after hematopoietic stem cell transplantation (HSCT). Natural killer (NK) cell immunotherapy may enhance graft-versus-leukemia (GvL) effects without increasing graft-versus-host disease (GvHD). This study assessed the safety and feasibility of early post-HSCT prophylactic infusions of third-party NK cells in high-risk AML. METHODS: In a single-arm, non-randomized trial, 11 high-risk AML patients received two doses of ex vivo expanded third-party NK cells (5 × 10⁶ cells/kg) on days 6 and 12 post-HSCT. Endpoints included safety (CTCAE v5.0), relapse incidence, overall survival (OS), and disease-free survival (DFS). NK cell products were assessed for purity (≥ 80% CD56⁺CD3⁻), cytotoxicity (K562 assay), and expansion. RESULTS: NK cell infusion was well tolerated, with no grade 3 or higher infusion-related toxicities. Acute GvHD (Grade 1-2) occurred in 36.4% (4/11); chronic GvHD in 27.3% (3/11). CMV reactivation occurred in 45.5% (5/11) and was managed preemptively. At a median 256-day follow-up (54-514), Relapse occurred in 27.3% (3/11; median: 111 days). Survival was significantly better in patients in CR1/CR2 at HSCT (83.3%) compared to those not in remission (20%; p = 0.02). CONCLUSION: Early prophylactic NK cell infusions post-HSCT are safe and feasible. Although relapse incidence remains substantial, outcomes appear improved versus historical data. Future randomized trials must confirm clinical benefits and refine timing/dosing strategies.