Efprezimod Alfa (CD24Fc, MK-7110) for the Prevention of Acute Graft Versus Host Disease (GVHD) Following Myeloablative Hematopoietic Stem Cell Transplantation (HSCT) (MK-7110-005)

Inclusion Criteria:

1. A prospective participant for allogeneic HCT for a malignant hematologic disorder.
2. The donor and recipient must have a human leukocyte antigen (HLA)-8/8 allelic match at the HLA-A, -B, -C, and - DRB1 loci. High-resolution typing is required for all alleles for unmatched donors. Only matched unrelated donors are acceptable for this trial.
3. The following diagnoses are to be included:

   1. Acute Myeloid Leukemia (AML) or Acute Lymphoblastic Leukemia (ALL) in first or second remission. Remission is defined as the absence of blasts in the peripheral circulation at the time of enrollment, \< 5% blasts in the bone marrow and absence of extramedullary disease including CNS involvement.
   2. Myelodysplastic syndrome (MDS) with intermediate or high-risk International Prognostic Scoring System (IPSS) or equivalent Revised International Prognostic Scoring System (IPSS-R) score with \< 10% blasts in the bone marrow.
4. Males or non-pregnant, non-lactating females, ≥ 18 years of age. Note there is no defined upper age limited, so long as deemed appropriate candidate for myeloablative conditioning.
5. Karnofsky Performance Status \>70%.
6. Participants must have normal or near normal organ function as defined by their treating institutions bone marrow transplant (BMT) program clinical practice guidelines. In addition, for purposes of this protocol minimum organ function criteria within 30 days of beginning conditioning include: Eligibility According to Pre HCT Organ Function:

   1. Total bilirubin ≤2.5 mg% (unless from Gilbert's disease or disease-related);
   2. Aspartate aminotransferase (AST) (serum glutamic-oxaloacetic transaminase (SGOT))/ alanine aminotransferase (ALT) (serum glutamic-pyruvic transaminase (SGPT)) \<5.0 X institutional upper limit of normal;
   3. Estimated or actual glomerular filtration rate (GFR)\>50 mL/min/1.73 m2 for participants with creatinine levels above institutional normal (GFR should be corrected for BSA);
   4. Pulmonary Function Tests include diffusing capacity of the lungs for carbon monoxide (DLCO), forced expiratory volume in one second (FEV1), forced vital capacity (FVC)\> 50% DLCO should be corrected for hemoglobin;
   5. Ejection Fraction \>50%;
   6. Hematopoietic Cell Transplantation-Specific Comorbidity Index (HCT-CI) ≤ 5.

   Item d and e may be assessed up to 10 weeks prior to the start of conditioning therapy.
7. Ability to understand and the willingness to sign a written informed consent document.
8. Women of child bearing potential and men must agree to use contraception prior to study entry and through day 100 post HCT (hormonal or barrier method of birth control; abstinence). Should a woman become pregnant or suspect she is pregnant while she or her partner is on treatment in this study, she should inform her study physician immediately. Men treated or enrolled on this protocol must also agree to use adequate contraception prior to the study until day 100 post HCT.

Exclusion Criteria:

1. Subjects may not have presence of active central nervous system (CNS) disease or extramedullary disease.
2. Prior cytotoxic chemotherapy within 21 days from the initiation of HCT conditioning (i.e. intensive induction / consolidation for AML). Note, certain low intensity treatments not intended to induce remission but rather stabilize disease are acceptable up to 24 hrs prior to initiation of HCT conditioning (i.e. Tyrosine Kinase Inhibitor, sorafenib).
3. Cord blood and haploidentical donors are not eligible.
4. HLA-mismatch at the HLA-A, -B, -C, and - DRB1 loci. Note, HLA-DQ mismatches are permissible.
5. Pregnant and nursing mothers are excluded from this study. This is because the risk to the fetus is unknown.
6. Any physical or psychological condition that, in the opinion of the investigator, would pose unacceptable risk to the participant or raise concern that the participant would not comply with protocol procedures.
7. Uncontrolled infections. Participants still under therapy for presumed or proven infection are eligible provided there is clear evidence (radiologic, clinical and/or culture) that the infection is well controlled.
8. Participants seropositive or polymerase chain reaction (PCR) positive for the human immunodeficiency virus (HIV). Participants with evidence of Hepatitis B or Hepatitis C PCR positivity.
9. Prior HCT (allograft or prior autograft).
10. Use of T cell depletion either ex vivo or in vivo (i.e. anti-thymocyte globulin (ATG), alemtuzumab) is prohibited.
11. Current or prior diagnosis of antecedent Myelofibrosis is excluded.