This study is a prospective, phase II clinical trial with the primary objective of assessing the effectiveness of demethylating agents combined with venetoclax in the prevention of recurrence after allogeneic hematopoietic stem cell transplantation (allo-HSCT) of high risk T-lymphoblastic lymphoma/leukemia (T-LBL/ALL) patients.

The experimental group included high risk T-ALL/LBL patients after allo-HSCT, who received relapse prevention treatment with demethylating agents such as azacitidine or decitabine, combined with venetoclax.

The historical control consisted of high-risk T-ALL/LBL patients who received allo-HSCT but did not receive any prophylactic treatment from multiple centers, and their basic information, disease information, treatment details, and efficacy data were collected. Propensity score matching was conducted with historical data to compare the advantages and disadvantages of the experimental regimen with the control group.

The primary endpoint was the relapse-free survival(RFS) rate after prophylaxis, while secondary endpoints included cumulative incidence of relapse (CIR), overall survival (OS), and the GVHD-relapse-free survival (GRFS). This study aims to provide a effective and safer prophylaxis treatment for high-risk T-LBL/ALL patients after all-HSCT.

Inclusion Criteria:

• 1.14-55 years old, male,or female.
• 2.Patients with allo-HSCT due to T-LBL/ALL, the donor type is not limited.
• 3.ECOG score is 0-2 points.
• 4.Blood routine: ANC ≥ 1.0 × 109/L, PLT ≥ 50 × 109/L.
• 5.One of the following high-risk factors:
• a. Age of initial diagnosis ≥ 35 years old.
• b. Initial diagnosis of WBC ≥ 100 × 109/L.
• c. Initial diagnosis of LDH exceeding the upper limit of normal values.
• d. Initial diagnosis of bone marrow involvement (blast cells ≥ 5%).
• e. Initial diagnosis of a bulky in the mediastinum (longest diameter ≥ 10cm).
• f. ETP immunophenotype.
• g. During the induction chemotherapy process, 2 courses did not achieve partial remission and/or 4 courses did not achieve complete remission.
• h. Residual lesions before transplantation: Flow cytometry analysis showed that the proportion of abnormal lymphoid cells in the bone marrow was greater than 0.01%; Positive detection of minimal residual lesions in molecular biology; PET-CT scan shows that residual lesions are still active.
• i. Based on the ELN recommendation based on adult T-ALL: gene mutations involving myeloid related genes, RAS/PI3K/AKT, JAK/STAT signaling pathway, and epigenetics, such as FLT3, NRAS/KRAS, PTEN, IL7R, JAK1, JAK3, DNMT3A, IDH1, IDH2; TP53, BCL2 mutations; t (8; 14) (q24; q11)/MYC rearrangement; t (7; 19) (q34; p13)/TCR-LYL1，TCR-MEF2C; del(5q) (q14).
• j. High risk subgroups based on NGS definition: PI3K signaling pathway/NRAS, KRAS/TP53/IKZF1/DNTM3A/IDH1, IDH2 gene mutation with or without NOTCH1, FBXW7/PHF6/EP300 gene mutation.

Exclusion Criteria：

• 1.Central involvement during any course of the disease.
• 2.Patients who have not achieved complete remission before transplantation.
• 3.Identify those with available targeted drugs.
• 4.For those who are resistant to BCL-2 inhibitors before transplantation, if the disease progresses during the application process, or if 3-4 courses of induction therapy containing BCL2 inhibitors do not improve.
• 5.Individuals who are known to be allergic to demethylating drugs or venetoclax.
• 6.Individuals with grade 2 or more degrees of active acute GVHD.
• 7.Individuals with moderate to severe chronic GVHD.
• 8.T-LBL/ALL relapse (flow cytometry abnormal lymphocyte cell proportion>0.01%, WT1 positive, fusion gene positive, or extramedullary recurrence), or transplant rejection, bone marrow donor cell chimerism<95%.
• 9.Blood routine: ANC<1.0 × 109/L or PLT<50 × 109/L.
• 10.Combined with severe organ dysfunction; The ratio of aspartate aminotransferase (AST)/alanine aminotransferase (ALT) is more than 3 times the normal value or the normal value of direct bilirubin is more than 3 times; The endogenous creatinine clearance rate (Ccr) is less than 50mL/min or 1.5 times the normal value of blood creatinine, regardless of whether hemodialysis treatment is used.
• 11.Merge severe active infections.
• 12.Pregnant or lactating women.
• 13. Accepting other investigational drugs.
• 14.According to the researchers' assessment, the patient may have complications that could lead to other dangers.