ORIGINAL RESEARCH article
Front. Med.
Sec. Hematology
Volume 12 - 2025 | doi: 10.3389/fmed.2025.1638176
This article is part of the Research TopicFuture Directions and Current Trends in Cellular TherapiesView all 3 articles
Clinical efficacy and safety of venetoclax combined with hypomethylating agents in relapsed high-risk acute myeloid leukemia patients after allogeneic hematopoietic stem cell transplantation
Provisionally accepted
- Nanfang Hospital, Southern Medical University, Guangzhou, China
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Patients experiencing relapse following allogeneic hematopoietic stem cell transplantation (allo-HSCT) for high-risk myeloid malignancies represent a therapeutic challenge with limited options. This multicenter single-center retrospective analysis evaluated 106 consecutive patients with post-transplant AML recurrence (2020-2024), comparing BCL-2 inhibition combined with hypomethylating agents (n=53) versus intensive chemotherapy (n=53). The experimental regimen demonstrated superior efficacy, achieving complete remission in 56.6% versus 26.4% (P=0.002) of cases. Survival analysis revealed significant advantages for the targeted approach, with median overall survival extending to 12.6 months compared to 5.8 months (HR 0.42, P<0.001). Molecular monitoring showed enhanced measurable residual disease clearance (70.0% vs 35.7%, P=0.021). The safety profile favored the venetoclax-based strategy, exhibiting reduced severe cytopenias (36.8% vs 64.2%, P=0.002) and fewer infectious complications (11.3% vs 32.1%, P=0.008). Multivariable modeling confirmed the regimen as an independent predictor for survival benefit (adjusted HR 0.42, 95% CI 0.31-0.58). The venetoclax-hypomethylating agent combination demonstrates clinically meaningful efficacy, achieving a 56.6% complete remission rate and 12.6-month median overall survival, with a favorable safety profile in this high-risk population.These findings establish venetoclax-epigenetic therapy as an effective salvage option for post-transplant relapse, particularly benefiting patients with molecularly high-risk disease or contraindications to intensive chemotherapy. The results warrant validation in prospective randomized trials to further define its role in this challenging clinical scenario.
Keywords: Myeloid neoplasia, cytotoxic regimens, therapeutic resistance, Disease recurrence, venetoclax
Received: 03 Jun 2025; Accepted: 26 Aug 2025.
Copyright: © 2025 Cheng, Fu, Jiang, Huang, Zhang, Long and Jiang. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Xuejie Jiang, Nanfang Hospital, Southern Medical University, Guangzhou, China
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