Early Chidamide Maintenance After Allogeneic Hematopoietic Stem Cell Transplantation in High‐Risk Myeloid Malignancies: A Prospective Cohort With Time‐Dependent External‐Control Analysis

Chidamide is an oral histone deacetylase inhibitor whose use as early maintenance after allogeneic hematopoietic stem cell transplantation (HSCT) remains insufficiently defined. This prospective single-center Phase 1/2 cohort included all 47 patients enrolled and treated by March 31, 2026. The Phase 2 primary endpoint was 2-year leukemia-free survival (LFS). An exploratory observational comparison used 23 platform-compatible historical comparators, time-dependent maintenance exposure, and propensity-score overlap weighting. Both cohorts received chidamide-containing conditioning. No formal multiplicity adjustment was applied. Treated-cohort 2-year LFS was 78.6% (95% confidence interval [CI], 63.9%-87.9%). In the main weighted model, maintenance exposure was associated with lower hazards of death (hazard ratio [HR], 0.29; 95% CI, 0.09-0.96) and relapse or death (HR, 0.24; 95% CI, 0.09-0.63). LFS associations were more consistent across sensitivity analyses; overall survival was less stable in landmark analyses. Graft-versus-host disease-free/relapse-free survival remained inconclusive. Maintenance began a median of 16 days after HSCT; 45 of 47 patients reached 20 mg twice weekly, and 35 completed 365 days. Grade 3-4 treatment-emergent adverse events were documented in 37 patients, predominantly cytopenias. One patient died during maintenance from infection with transplant-associated thrombotic microangiopathy; the relationship to chidamide was not determined. Relapse, non-relapse mortality, and lymphocyte subset recovery were descriptive. Maintenance was deliverable with active dose management. Trail Registration: ClinicalTrials.gov identifier: NCT05682755.