Abstract
BACKGROUND AND PURPOSE: Acute myeloid leukemia (AML) is an aggressive disease with suboptimal overall survival, especially in relapsed/refractory patients. The primary goal of salvage therapy in this patient is to achieve optimal disease control, thereby allowing the transition to hematopoietic stem cell transplantation (HSCT), which remains the only curative option for a subset of these patients. Allogeneic KIR ligand-mismatched CD56(+) NK/NKT-like cells have demonstrated antileukemic activity and represent a promising platform for the development of novel cellular therapies. STUDY DESIGN: Relapsed/refractory non-M3 AML patients who were not HSCT candidates were included in this phase I clinical trial. Patients received the FLAG conditioning regimen followed by three escalating doses (1 × 10⁶, 3 × 10⁶, 5 × 10⁶ cells/kg) of CD56(+) NK/NKT-like cells at 5-day intervals. RESULTS: A total of 11 patients with a median age of 41.5 years were enrolled in the study. On average, they received three lines of prior chemotherapy and showed 18% blasts in their bone marrow. The infusion of CD56⁺ NK/NKT-like cells was safe, with no serious toxicity or graft-versus-host disease (GVHD) observed in any patient. Following this treatment protocol, five patients (45.4%) achieved complete remission (CR), with or without hematologic count recovery. Four of these patients (36.3%) underwent successful HSCT and remained event-free to the end of the follow-up period. CONCLUSION: Overall, these trials indicated that the FLAG regimen chemotherapy combined with allogeneic KIR ligand-mismatched CD56(+) NK/NKT-like cell infusion is safe and may serve as an effective bridge to HSCT in 36.3% of patients with refractory/relapsed non-M3 AML.