Hypomethylating Agent and Venetoclax After Allo-HSCT in Patients With High-risk Myeloid Malignancies.

This is a prospective single-arm study. Patients with high-risk AML or MDS aged between 18-70 years old will enroll in the study. They will be given hypomethylating agents (azacytidine 32mg/m2 or decitabine 5mg/m2) for 5 days and venetoclax 400mg/d for 7 days after allogeneic hematopoietic stem cell transplantation. The maintenance therapy will start from 60th days posttransplant, repeated every 28 days until up to 1-year posttransplant. The 1-year leukemia-free survival rate，1-year cumulative recurrence rate, and 1-year overall survival will be analyzed.

Inclusion criteria

• Patients with AML or MDS and have received allogeneic hematopoietic cell transplantation;
• Patients with AML must have one of the following high-risk factors: Cytogenetics and molecular features consistent with adverse risk group by European LeukemiaNet classification for AML； require more than 2 courses of induction chemotherapy to reach complete remission； Extramedullary myeloid malignancy；≥CR2； Presence of measurable residual disease at the time of HSCT. *
• Patients with MDS must have one of the following high-risk factors: IPSS-R scores are high-risk or very high-risk； Presence of TP53 mutation； Presence of measurable residual disease at the time of HSCT. *
• CBC: ANC ≥ 1.0 × 10e9/L, Hb ≥ 80g/L, and PLT ≥ 50 × 10e9/L；
• Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2.

• Presence of measurable residual disease at the time of HSCT is defined as the following: Blast percentage in bone marrow detected by flow cytometry ≥0.01%； Presence of fusion gene or mutated gene by qPCR.

Exclusion criteria

• Concurrent use of targeted drugs ;
• Resistant to Venetoclax before transplantation;
• Allergic to decitabine , Azacitidine or venetoclax;
• Active grade II or higher acute GVHD ;
• Active moderate or severe chronic GVHD ;
• Diseases recurrence (abnormal myeloid cells detected by flow cytometry >0.01%, presence of WT1 or other genes, or extramedullary malignancy ), percentage of donor cells in bone marrow <90% or graft rejection:
• CBC: ANC < 1.0 × 10e9/L, or PLT < 50 × 10e9/L；
• Severe organ dysfunction: Elevated Aspartate transaminase (AST) /alanine transaminase (ALT), or direct bilirubin >3 times upper limit of normal; Creatinine clearance (Ccr)<50mL/min or serum creatinine >1.5 times upper limit of normal, whether hemodialysis treatment is performed;
• Active uncontrolled systemic fungal, bacterial, or viral infection
• Pregnant or lactating women;
• Other severe complications and not suitable judged by researchers.