Azacitidine Combined with Donor Lymphocyte Infusion for Acute Myeloid Leukemia Post-transplant Relapse Prevention.

1.Basic solution: Azacitidine is administered subcutaneously at 32 mg/m2/d for five consecutive days, starting no earlier than day +90 after HSCT, then repeated every 28 days for a total of twelve cycles. DLI is administered after an interval of 48 hours. Prophylactic DLI is given in escalating doses every four to six weeks for a total of three to four doses.The initial dose of DLI for haploid transplant patients is 1×10^5 CD3+/kg receptor weight lymphocytes gradually increased to 5×10^5, 1×10^6 and (2~5)×10^6 CD3+ Lymphocytes.

• Start time of medication: +90 ~ +120 days after transplantation.
• Donor lymphocyte infusion was preceded by anti-anaphylaxis,such as promethazine and hormone therapy was prohibited.
• In the course of AZA and DLI intervention, other targeted drugs such as venetoclax or chemotherapy drugs can be added on the basis of AZA if MRD or MRD increase (>1log) ,DLI continues as planned.

2.Stop treatment: Occurrence of any of the following conditions:

• Life-threatening complications.
• Acute GVHD above II degree; chronic GVHD above moderate manifestations or overlapping syndrome; No chronic GVHD is observed if acute GVHD remission is observed after discontinuation for 1 to 2 months, then preventive treatment is started again .
• Hematologic recurrence, graft rejection or bone marrow donor chimerism <90%.

Inclusion criteria

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Patients enrolled must meet the following criteria:

• ≥18 years old and ≤70 years old, male or female;
• Patients with haploid peripheral blood stem cell transplantation of AML;
• All patients received BU based myeloablative conditionings;
• A diagnosis of high-risk AML is one of the following:

① Patients without morphologic CR before transplantation, including patients with initial refractory disease and recurrence.

② AML with poor prognosis (Standardized diagnosis and prognostic stratification of acute myeloid leukemia based on ELN edition which was 2022 Year) .

• Blood routine: neutrophils ≥1×10^9/L, platelet ≥50.0×10^9/L;
• There is no active grade II or higher acute GVHD or moderate or severe chronic GVHD;
• The ECOG score is 0 to 2;
• Donor lymphocytes are available;
• The patient must be able to understand and be willing to participate in the study and sign an informed consent form.

Exclusion criteria

• Possible subjects who meet any of the following criteria will be excluded from the trial:

• Those who are allergic to known azacitidine or interferon
• Patients with active acute GVHD;
• Patients with moderate or more chronic GVHD;
• Non-haploid donor transplants;
• Patients who have not achieved complete remission after transplantation;
• AML recurrence after transplantation (bone marrow, peripheral blood primitive cells ≥5% or extramedullary recurrence), or graft rejection, bone marrow donor cell chimeric rate (STR) <90%;
• Patient blood routine: ANC<1.0×10^9/L or PLT<50×10^9/L;
• Combined with severe organ dysfunction:liver function (AST/ALT) >3 times normal upper limit; the direct bilirubin > 3 times normal upper limit; renal function (Cr) < 50mL/min or >1.5 times normal upper limit, regardless of hemodialysis treatment;
• Patient with severe active infection;
• Pregnant or lactating women;
• Have received other interventions or are receiving other research drugs before the study begins;
• At the discretion of the investigator, other dangerous complications may result.