SHR2554/AZA + Overlapped TBF for High-risk/Relapsed Leukemia/MDS

Inclusion Criteria:

1. Age 15-60 years, of either sex.
2. Diagnosis of AML or ALL according to the WHO 2022 criteria, with an indication for allogeneic hematopoietic stem cell transplantation: AML with high-risk genetics at diagnosis (risk stratification per ELN 2022) or relapsed/refractory AML (meeting any of the following: refractory-failure to achieve complete remission (CR) after two cycles of induction chemotherapy; relapse-reappearance of blasts in peripheral blood or bone marrow (≥5%) after first CR, or extramedullary relapse (EMR)). High-risk B-ALL at diagnosis (risk stratification per ELN 2022) or pre-transplant MRD-positive B-ALL. Confirmed T-ALL. History of central nervous system leukemia (CNSL) or pathologically confirmed extramedullary disease (EMD) during AML or ALL. Myelodysplastic neoplasms (MDS): IPSS score intermediate-2 or high; IPSS-R score high or very high; IPSS-M score high or very high.
3. Availability of an appropriate HLA-matched donor.
4. ECOG performance status 0-2.
5. Adequate major organ function, defined as: Left ventricular ejection fraction ≥50%. Pulmonary function: DLCO ≥50% of predicted value. Liver function: ALT/AST ≤3×ULN, total bilirubin ≤2×ULN. Renal function: estimated creatinine clearance (CrCl) ≥60 mL/min.
6. Ability to understand the study and voluntary signed informed consent.

Exclusion Criteria:

1. Acute promyelocytic leukemia (APL);
2. Active central nervous system leukemia;
3. Prior allogeneic hematopoietic stem cell transplantation;
4. Prior treatment with any EZH2 inhibitor;
5. Uncontrolled active infection as assessed by the investigator;
6. Myocardial infarction or unstable angina within the previous 6 months;
7. Known hypersensitivity to Zeprumetostat, azacitidine, or any excipient of the mBuCy regimen;
8. Pregnant or breastfeeding women;
9. Any other medical condition that, in the investigator's judgment, would preclude study enrollment.