This study aims to evaluate the safety and efficacy of a Venetoclax and hypomethylating agent-based regimen combined with infusion of HLA-mismatched donor G-CSF mobilized peripheral blood mononuclear cells (GPBMC) in patients with intermediate-risk and higher myelodysplastic syndromes who are ineligible for allogeneic hematopoietic stem cell transplantation.
Age >=18 years, male or female, non-limited by race or ethnicity.
Confirmed diagnosis of MDS according to the World Health Organization (WHO) 5th edition classification, based on histopathology and cytogenetics.
Risk stratification according to the Revised International Prognostic Scoring System (IPSS-R) must place the patient in the intermediate-, high-, or very high-risk category.
Not candidates for or refuse allogeneic hematopoietic stem cell transplantation.
Uncontrolled infection or hemorrhage.
Cardiovascular disease with clinical significance, such as uncontrolled or highly symptomatic cardiac arrhythmias, congestive heart failure, or myocardial infarction within 6 months prior to screening, or New York Heart Association (NYHA) function class 3 (moderate) or class 4 (severe) heart disease.
Uncontrolled autoimmune disease or requiring immunosuppression treatment.
History of severe blood infusion reaction.
Single group
Venetoclax
DrugGiven PO. For the first cycle, dose of 100 mg on Day 1, 200 mg on Day 2, and 400 mg on Days 3-14. For other cycles, dose of 400 mg on Days 1-14. Note: The dose should be reduced to 100-200 mg daily if concomitant azole antifungals are required.
Azacitidine (AZA) or Decitabine (DAC)
DrugAZA: Given SC. Dose of 75 mg/m² on Days 1-7 of each cycle. DAC: Given IV. Dose of 20 mg/m² on Days 1-5 of each cycle.
GPBMC infusion
Biological/VaccineHLA-mismatched donor GPBMCs are infused on Day 15.
Overall survival (OS)
OS is defined as the number of days from the date of study entry to the date of death.
Overall response rate (ORR)
ORR is defined as complete remission (CR) (or CR equivalent) + partial remission (PR) + CR with limited count recovery (CRL) + CR with partial hematologic recovery (CRh) + hematologic improvement (HI) according to IWG 2023 criteria.
Modified overall response (mOR)
Modified OR is defined as CR+PR+CRL+CRh.
Complete remission (CR)
CR is defined as absolute neutrophil count \> 1 × 109/L, platelet count \> 100 × 109/L, Hb ≥10 g/dL, bone marrow with \< 5% blasts, and PB blasts 0%.
Partial remission (PR)
PR is defined as decrease of at least 50% in the percentage of blasts still ≥5% in the bone marrow, peripheral blood neutrophil count \> 1 × 109/L, platelet count \> 100 × 109/L, Hb ≥10 g/dL.
CR with limited count recovery (CRL)
CRL is defined as bone marrow with less than 5% blasts, PB blasts 0%, and PB only meeting 1 or 2 of the following: absolute neutrophil count \> 1 × 109/L, platelet count \> 100 × 109/L, Hb ≥10 g/dL.
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