MRD-driven HDACi-based therapy post-transplant: a real-world study in high-risk acute myeloid leukemia.

Authors

Wei Ling, Ping Wu, Suijing Wu, Chengwei Luo, Lisi Huang, Xiaomei Chen, Xiaoling Liang, Zhilun Li, Ruohao Xu, Jiaqi Tan, Jinghua Wang, Peilong Lai, Xin Du, Jianyu Weng

Published in

Annals of hematology. Jul 13, 2026. Epub Jul 13, 2026.

Abstract

Relapse remains a major challenge limiting long-term survival in patients with acute myeloid leukemia (AML) after allogeneic hematopoietic stem cell transplantation (allo-HSCT). Measurable residual disease (MRD) is a critical independent prognostic predictor in high-risk AML. While MRD-driven prophylactic or preemptive interventions hold promise for relapse prevention, optimal therapeutic strategies remain lacking. We investigated the efficacy and safety of chidamide, a selective histone deacetylase (HDAC) inhibitor with dual epigenetic and immunomodulatory properties, within MRD-adapted post-transplant strategies in high-risk AML.
This pilot study analyzed 43 consecutive AML patients with high-risk AML, including pre-transplant relapsed/refractory or MRD-positive, or post-transplant MRD-positive who received Chidamide-based therapy after allo-HSCT between December 2020 and July 2023. Patients who were MRD-negative post-transplant (n=17) received prophylactic therapy, while those who were MRD-positive or relapsed post-transplant (n=26) underwent preemptive intervention. Primary endpoints included relapse-free survival (RFS) and overall survival (OS). Secondary endpoints included MRD negativity rates, toxicity (CTCAE v5.0), and changes in peripheral blood lymphocyte subsets. Statistical analyses employed Kaplan-Meier methods and Log-rank tests for survival, Chi-square/Fisher's exact tests for categorical variables, and paired t-tests for lymphocytes subsets.
At a median follow-up of 742 days, the overall sustained remission rate was 60.4%. In the preemptive group, Chidamide-based therapy achieved an 88.5% MRD conversion rate from positive to negative (median time to conversion: 50 days), with 65% maintaining sustained negativity. The prophylactic group demonstrated a 58.8% sustained MRD-negative rate. The 6-month and 1-year RFS and OS rates for the entire cohort were 79%, 69.8% and 100%, 72.1%, respectively. No statistically significant difference in RFS or OS was observed between the preemptive and prophylactic groups (P>0.05 for both). Grade 3/4 hematologic toxicities occurred in 32.6% (neutropenia) and 20.9% (thrombocytopenia) of patients, with no GVHD exacerbation observed. Chidamide treatment significantly increased peripheral blood CD8+ T cells (P=0.033) while reducing CD4+ T cells (P=0.007), suggesting enhanced cytotoxic potential.
Chidamide-based MRD-driven therapy demonstrates promising durable MRD eradication and clinically relevant survival rates in high-risk AML patients post transplant, potentially mediated by its dual epigenetic and immunomodulatory effects, including T-cell modulation. While limited by its retrospective nature and single-center design, these real-world findings support further investigation of HDAC inhibitor-based MRD-directed algorithms in prospective studies (NCT06066905).

PMID:
42439986
Bibliographic data and abstract were imported from PubMed on 13 Jul 2026.

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