{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T16:26:38Z","timestamp":1790267198749,"version":"4.1.0"},"reference-count":27,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,9,15]],"date-time":"2025-09-15T00:00:00Z","timestamp":1757894400000},"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. Med."],"abstract":"<jats:sec><jats:title>Introduction<\/jats:title><jats:p>Relapse after allogeneic hematopoietic stem cell transplantation (allo-HSCT) for high-risk myeloid malignancies remains a major therapeutic challenge, with conventional chemotherapy offering limited survival benefits. BCL-2 inhibition combined with hypomethylating agents (HMAs) has emerged as a potential therapeutic option, but comparative data in this setting are scarce.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We conducted a single-center retrospective study of 106 consecutive patients with post-transplant acute myeloid leukemia (AML) recurrence treated between 2020 and 2024. Patients received either venetoclax plus HMAs (<jats:italic>n<\/jats:italic>\u202f=\u202f53) or intensive chemotherapy (<jats:italic>n<\/jats:italic>\u202f=\u202f53). Outcomes assessed included complete remission (CR) rate, overall survival (OS), measurable residual disease (MRD) clearance, and treatment-related toxicities. Multivariable Cox regression analysis was performed to evaluate survival predictors.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>The venetoclax-based regimen achieved significantly higher CR rates (56.6% vs. 26.4%, <jats:italic>p<\/jats:italic>\u202f=\u202f0.002) compared with intensive chemotherapy. Median OS was markedly improved with venetoclax plus HMAs (12.6 vs. 5.8 months; HR 0.42, <jats:italic>p<\/jats:italic> &amp;lt; 0.001). MRD clearance was more frequent in the venetoclax group (70.0% vs. 35.7%, <jats:italic>p<\/jats:italic>\u202f=\u202f0.021). Safety analysis demonstrated lower incidences of severe cytopenias (36.8% vs. 64.2%, <jats:italic>p<\/jats:italic>\u202f=\u202f0.002) and infectious complications (11.3% vs. 32.1%, <jats:italic>p<\/jats:italic>\u202f=\u202f0.008). Multivariable modeling confirmed venetoclax-based therapy as an independent predictor of improved survival (adjusted HR 0.42, 95% CI 0.31\u20130.58).<\/jats:p><\/jats:sec><jats:sec><jats:title>Discussion<\/jats:title><jats:p>Venetoclax in combination with HMAs provided superior clinical benefits over intensive chemotherapy in post-allo-HSCT AML relapse, achieving higher remission rates, improved survival, enhanced MRD clearance, and a favorable safety profile. These findings highlight venetoclax-based regimens as a promising therapeutic approach for this high-risk population.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fmed.2025.1638176","type":"journal-article","created":{"date-parts":[[2025,9,15]],"date-time":"2025-09-15T05:29:03Z","timestamp":1757914143000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":5,"title":["Clinical efficacy and safety of venetoclax combined with hypomethylating agents in relapsed high-risk acute myeloid leukemia patients after allogeneic hematopoietic stem cell transplantation"],"prefix":"10.3389","volume":"12","author":[{"given":"Jiaying","family":"Cheng","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haipeng","family":"Fu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ling","family":"Jiang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yun","family":"Huang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yujiao","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhiquan","family":"Long","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xuejie","family":"Jiang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2025,9,15]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tcb.2025.04.006","article-title":"Translational 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