Interferon-γ (IFN-γ) With Donor Leukocyte Infusion to Treat Relapsed Acute Myeloid Leukemia and Myelodysplastic Syndromes Post Allogeneic Hematopoietic Stem Cell Transplantation

Inclusion Criteria: 1. Age ≥ 18 years 2. Recipients of an alloSCT for AML or MDS from a minimally 8/8 HLA-matched donor (Cohort 1: HLA -matched alloSCT recipients) or recipients of a haploidentical donor SCT for AML or MDS from a minimally 4/8 HLA-matched donor (Cohort 2: Haplo-SCT recipients) 3. AML/MDS relapsed post-alloSCT with measurable residual disease defined by either of the following criteria: 1. At least 5% or more myeloblasts based on bone marrow biopsy morphology by pathologist review. Abnormal myeloblasts cannot not exceed 30% overall 36 2. At least 0.1% of abnormal myeloblasts with a leukemia-associated immunophenotype (LAIP) by multiparameter flow cytometry. The abnormal cells with LAIP should not exceed 30% of nucleated cells. 3. Recurrent or persistent cytogenetic abnormalities detectable by FISH or karyotype analysis. 4. For patients with mutant NPM1, at least 1,000 mutant transcript copies per 106 ABL or equivalent housekeeping transcripts in bone marrow by qPCR or dPCR 4. Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) 0-2 5. A DLI is available, or the donor is available and agrees to undergo apheresis to collect lymphocytes for infusion 6. If salvage therapy for post-alloSCT relapse was received, the therapy is limited to 1 line of the following: 1. For hypomethylating agents, venetoclax, and targeted therapies (e.g., tyrosine kinase inhibitors, IDH1/IDH2 inhibitors, or FLT3 inhibitors), the last dose must be \> 2 week prior to the initiation of IFN-γ 2. For cytotoxic chemotherapy agents, the last dose must be \>2 weeks prior to start of treatment for the present study 3. For investigational agents, the last dose must be ≥ 4 weeks or 5 half-lives (whichever is longer) prior to the start of treatment for the present study 7. Provision of signed and dated informed consent form 8. Stated willingness to comply with all study procedures and availability for the duration of the study 9. For female subject, who is \< 55 years old without hysterectomy, oophorectomy or documented menopause, willingness to use two forms of contraception including one form of highly effective contraception (i.e., long-acting reversible contraception, oral contraceptive pills) for the duration of the study 10. For male subject, willingness to use highly effective contraception methods including male condoms by male subject and one form of highly effective contraception by his female partner (i.e., long-acting reversible contraception, oral contraceptive pills) for the duration of the study Exclusion Criteria: 1. Primary engraftment failure after alloSCT 2. Evidence of mixed phenotype leukemia with lymphoid differentiation (Cohort 1: HLA -matched alloSCT recipients) 3. Grade 3 or 4 aGVHD per Mount Sinai Acute GVHD International Consortium (MAGIC) at the time of planned enrollment 4. History of grade 4 aGVHD per the MAGIC criteria 5. Moderate or severe cGVHD per NIH Consensus Criteria at time of planned enrollment 6. Any systemic immunosuppressive medications taken within 2 weeks before the enrollment 7. Grade 3 or higher non-hematologic toxicity related to any prior therapy at the time of enrollment 8. A contraindication to receive IFN-γ including a known hypersensitivity to IFN-γ, E. coli derived products or any other component of the product 9. Positive pregnancy test or currently breastfeeding on Day 1 of study treatment 37 10. Active cardiac arrhythmia not controlled by medical management or current NYHA class II or higher congestive heart failure within 2 months of enrollment unless it was due to a tachyarrhythmia which is under control at the time of enrollment 11. Active ischemic heart disease not controlled with medications within 2 months of enrollment 12. Acute or chronic pulmonary disease requiring continuous oxygen treatment 13. Seizure disorder not controlled by medications within 2 months of enrollment 14. AST or ALT \> 5x ULN or total bilirubin \>3x ULN at time of enrollment 15. Renal function CrCl \<30 mL/min at time of enrollment using modified Cockcroft-Gault formula 16. Detection of HLA loss of heterozygosity (LOH) in relapsed malignant cells. Specifically, there has been a loss of the mismatched set of HLA alleles encoded on chromosome 6 (ie uniparental disomy of chromosome 6), within 30 days prior to enrollment (Cohort 2: Haplo-SCT recipients)