Introduction
cancer, AML, hematologic malignancy
CANCER, DISEASE, HEMATOLOGIC MALIGNANCY, AML, SECONDARY
AML is a hematologic malignancy that frequently affects elderly individuals, with a median diagnosis age of 68 years. However, the survival rate within a five-year timeframe is only 26%, which is concerning [AML prognosis at a younger age is worst, and patient-related studies have shown that the disease is fatal in younger adults; however, bone marrow transplantation is well tolerated in young people, so advanced therapy with alloimmune cell transplantation might be very promising in this category [In recent decades, numerous methods have been explored to utilize NK cells in therapeutic applications [The most studied trial for NK cell transplantation is for haploidentical sources, and the safety and efficacy of allogeneic NK cell infusion were confirmed in patients with hematologic malignancy from haploidentical donors. The haploidentical selection was performed to avoid NK cell transplant rejection and potential immune stimulation. However, studies have proven that allogeneic cells are also well tolerated in the recipient’s body, which is due to killer-cell immunoglobulin-like receptors (KIRs) [Here, we report the results of a phase I adoptive cancer immune cell therapy with two infusions from ex vivo expanded random unrelated healthy donors PB-NK cells administered to patients with refractory/relapsed AML, which can result in some cells having a complete donor–recipient KIR ligand mismatch. This is a pilot study for safety and dose escalation analysis that focuses on the feasibility of production, administration, performance, safety, and follow-up for short-period efficacy analysis.We deliberately focused on the KIR mismatch in this pilot project to obtain evidence of the association of this characteristic with the intervention outcome. This approach not only permits the extended feasibility of MHC class I mismatch but also overcomes the limitations of small potential donor pools.The primary objectives were to determine the safety and feasibility of this adoptive cell therapy in patients with pre-conditioned AML, and the secondary objective was to evaluate the probable antitumor efficacy of PB-NK cells. This study should be executed as a non-randomized trial because it is a controlled study to evaluate the feasibility of production, implementation, safety, and access to patient follow-up, and blinding or randomization might complicate the evaluation of the main objective. One significant drawback of this study is its small sample size. It only provides sufficient data to assess feasibility. To obtain more accurate and comprehensive results, a phase 2 study with a one-year follow-up is necessary. However, the publication of these findings will take time, and we are passionate about reporting these preliminary data until phase II report completion.