Potential therapeutic roles of natural killer cells in acute myeloid leukemia: a systematic review study

Acute myeloid leukemia (AML) is a blood cancer caused by genetic mutations in hematopoietic precursor cells, leading to abnormal cell production in the bone marrow (BM) and results in complications like anemia, leukopenia, and thrombocytopenia. Treatments, such as chemotherapy and hematopoietic stem cell transplantation carry risks like graft-versus-host disease (GVHD) and infections due to immune suppression. Recently, treatment with natural killer (NK) cells has emerged as a novel approach for treating AML. NK cells can identify and destroy leukemic cells, and methods like NK cell transfer and cytokine activation show promise as effective treatments. This article evaluates the feasibility and safety of NK cell-based therapies for AML patients. This article is a systematic review that registered its protocol in PROSPERO. A strategic search was conducted in the PubMed, Scopus, Google Scholar, and Web of Science databases using the keywords "Natural killer cell, " "Acute myeloid leukemia" and "Immunotherapy". After removing duplicates and applying inclusion/exclusion criteria, 1623 articles were selected. Two reviewers screened titles and abstracts, followed by a full-text review. Disagreements were resolved by a third reviewer, resulting in 17 articles for inclusion. Data were organized in Excel, and study quality was assessed using the Cochrane risk-of-bias tool. Data analysis was performed using R software. Out of 1623 initially identified records, 17 clinical studies comprising 402 AML patients aged between 1 and 82 years were included. Most studies used allogeneic or homologous NK cells, sometimes combined with chemotherapy or interleukin-2. The pooled complete remission (CR) rate was 48.22% (95% CI 31.75-65.09%), with significant heterogeneity (I² = 76%). Immune response prevalence across 14 studies was 69.34% (95% CI 49.18-84.09%). Adverse events were generally mild and manageable, with no consistent reports of severe toxicity. Although study quality varied, eight studies demonstrated low risk of bias. Publication bias was detected for CR outcomes, adjusting the CR rate to 36.94% after correction. We conducted a systematic review that demonstrates that NK cell therapy shows promising efficacy and acceptable safety in treating AML patients, with a pooled complete remission rate of 48.22% and encouraging immune response rates. Despite heterogeneity across studies and varying methodological quality, the consistent observation of anti-leukemic effects and manageable adverse events supports the potential role of NK cell therapy as a complementary treatment. Further high-quality, large-scale trials are warranted to validate these findings and optimize clinical protocols.