eligibility_summary
Eligible: 18–70 with WHO MDS, IPSS‑M very high‑risk, suitable allo‑HSCT donor (related ≥5/10 or unrelated ≥8/10 HLA), HCT‑CI ≤2, ECOG 0–2, adequate organs (Cr ≤1.5×ULN, EF ≥50%, SpO2 >92%, bili ≤1.5×, ALT/AST ≤2×, DLCO ≥40%, FEV1 ≥50%), consent. Exclude: failed conditioning/reinfusion, prior HSCT, HCT‑CI ≥3 or ECOG >2, unstable cardio/cerebrovascular disease, PAH, uncontrolled infection, major neuro/psych illness, HIV, active HBV/HCV or HBV risk w/o antivirals, pregnant/breastfeeding, no contraception, allergy to azacitidine/decitabine/venetoclax.
trial_source
clinical_trials.gov from Dec 2, 2025
annotation_status
ai
ai_summary
Interventions: 1) Azacitidine + venetoclax (preferred). Azacitidine is a hypomethylating cytidine analog (epigenetic drug) that inhibits DNA methyltransferases, causing DNA hypomethylation, re-expression of silenced genes, differentiation, and cytotoxicity in MDS clones. Venetoclax is an oral small-molecule BH3-mimetic BCL-2 inhibitor that restores mitochondrial apoptosis in myeloid blasts. 2) Azacitidine or decitabine + donor lymphocyte infusion (DLI) for TP53-mutant or VEN-nonresponders. Decitabine is a deoxycytidine hypomethylating agent that inhibits DNMTs, DLI is adoptive immunotherapy with escalating donor CD3+ T cells to enhance graft-versus-leukemia. Targets/pathways: BCL-2–dependent survival signaling, DNA methylation/DNMT epigenetic dysregulation, residual MDS/AML blasts and stem/progenitor cells (including TP53-mutant clones), and immune-mediated clearance via donor T-cell cytotoxicity. Aim: relapse prevention post-allo-HSCT.