{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T05:55:40Z","timestamp":1790834140326,"version":"4.1.0"},"reference-count":50,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2021,8,16]],"date-time":"2021-08-16T00:00:00Z","timestamp":1629072000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:sec><jats:title>Background<\/jats:title><jats:p>Previous trials demonstrated evidence involving the total effects of gemtuzumab ozogamicin (GO), an anti-CD33 humanized antibody, on treating acute myeloid leukemia (AML). In this updated systematic review, meta-analysis, and network meta-analysis (NMA), we aimed to comprehensively explore the clinical benefits and safety of GO in various subtypes of AML.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>PubMed, Embase, Cochrane, and Chinese databases were filtered to search randomized controlled trials (RCTs) and retrospective cohort studies that compared clinical efficiency and toxicity of GO with non-GO groups in AML. Random-effects models were used to calculate pooled effect sizes and 95% confidence intervals (CIs). Relative risk (RR) was used for estimating complete remission (CR), early death, and toxicity. Hazard risk (HR) was accomplished to evaluate survival.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Fifteen RCTs and 15 retrospective cohort studies were identified (GO: 4,768; Control: 6,466). GO tended to improve CR (RR 0.95, p = 0.084), followed by significantly improved survival (overall survival: HR 0.86, p = 0.003; event-free survival: HR 0.86, p = 0.015; relapse-free survival: HR 0.83, p = 0.001; cumulative incidence of relapse: HR 0.82, p &amp;lt; 0.001). GO benefits of CR and survival were evident in favorable- and intermediate-risk karyotypes (p \u2264 0.023). GO advantages were also associated with nucleophosmin 1 mutations (p \u2264 0.04), wild-type FMS-like tyrosine kinase 3 internal tandem duplication gene (p \u2264 0.03), age of &amp;lt;70 years (p &amp;lt; 0.05), <jats:italic>de novo<\/jats:italic> AML (p \u2264 0.017), and CD33(+) (p \u2264 0.021). Both adding GO into induction therapy (p \u2264 0.011) and a lower (&amp;lt;6 mg\/m<jats:sup>2<\/jats:sup>) dose of GO (p \u2264 0.03) enhanced survival. Prognosis of combined regimens with GO was heterogeneous in both meta-analysis and NMA, with several binding strategies showing improved prognosis. Additionally, GO was related to increased risk of early death at a higher dose (\u22656 mg\/m<jats:sup>2<\/jats:sup>) (RR 2.01, p = 0.005), hepatic-related adverse effects (RR 1.29, p = 0.02), and a tendency of higher risk for hepatic veno-occlusive disease or sinusoidal obstruction syndrome (RR 1.56, p = 0.072).<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>These data indicated therapeutic benefits and safety of GO in AML, especially in some subtypes, for which further head-to-head RCTs are warranted.<\/jats:p><\/jats:sec><jats:sec><jats:title>Systematic Review Registration<\/jats:title><jats:p>[PROSPERO: <jats:uri>https:\/\/www.crd.york.ac.uk\/prospero\/<\/jats:uri>], identifier [CRD42020158540].<\/jats:p><\/jats:sec>","DOI":"10.3389\/fimmu.2021.683595","type":"journal-article","created":{"date-parts":[[2021,8,16]],"date-time":"2021-08-16T08:43:37Z","timestamp":1629103417000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":12,"title":["Clinical Benefits and Safety of Gemtuzumab Ozogamicin in Treating Acute Myeloid Leukemia in Various Subgroups: An Updated Systematic Review, Meta-Analysis, and Network 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