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

• SHR2554/AZA + Overlapped mBUCY (Drug): SHR2554 350 mg BID and azacitidine 75 mg/m² daily on days -9 to -3, overlapping with mBUCY conditioning:semustine 250 mg/m² on day -8; cytarabine 2 g/m² q12h on day -7; busulfan 0.8 mg/kg q6h on days -6,-5, -4 (total 3.2 mg/kg/day); cyclophosphamide 1.8 g/ m²/day on days -3 and -2.
• mBUCY conditioning Regimen Group (Drug): semustine 250 mg/m² on day -8; cytarabine 2 g/m² q12h on day -7; busulfan 0.8 mg/kg q6h on days -6,-5, -4 (total 3.2 mg/kg/day); cyclophosphamide 1.8 g/ m²/day on days -3 and -2

Primary outcomes

• Event-Free Survival (EFS) [1 years]: It is measured from the time of entry into this trial to the date of first event (relapse, death from any cause); patients not known to have experienced any event at last follow-up are censored on the date they were last known to be event-free.

Secondary outcomes

• Overall survival（OS） [2 years]: It is measured from the date of entry into this trial to the date of death from any cause; patients not known to have died at last follow-up are censored on the date they were last known to be alive.
• Cumulative incidence of relapse（CIR） [2 years]: It is measured the date from complete remission after transplantation to hematological relapse was recorded. Patients who had no relapse at the last follow-up were considered as censored data, and non-relapse death was regarded as a competing risk event.
• event-free survival (EFS) [2 years]: It is measured from the time of entry into this trial to the date of first event (relapse, death from any cause, or grade III-IV acute GVHD); patients not known to have experienced any event at last follow-up are censored on the date they were last known to be event-free.
• transplant related mortality (TRM) [2 years]: cumulative incidence of transplant related mortality
• graft-versus-host disease (GvHD) [2 years]: incidence and severity of acute (aGvHD) and chronic graft-versus-host disease (cGvHD) (aGvHD refer to Glucksberg Criteria and cGvHD refer to the National Institutes of Health Consensus)
• Time period for hematopoietic reconstruction [24 weeks]: Granulogenetic hematopoietic reconstitution: The absolute neutrophil count in peripheral blood needs to reach or exceed 0.5×10\^9 cells/L for 3 consecutive days. Megakaryotic hematopoietic reconstitution: platelet count needs to be more than 20×10\^9/L and does not rely on platelet transfusion for 7 consecutive days.
• Regimen related toxicity [2 years]: Number of participants with regimen related toxicity as assessed by CTCAE v5.0
• veno-occlusive disease (VOD) [2 years]: incidence of veno-occlusive disease (VOD) events (refer to modified Seattle Criteria of VOD)

Sex: All, ages: 18 Years to 65 Years

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 SHR2554, 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.