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Background <p>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.</p> Methods <p>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.</p> Results <p>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&gt;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.</p> Conclusion <p>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).</p>

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

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年7月13日

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  • 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

摘要

Background

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.

Methods

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.

Results

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.

Conclusion

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).