De-escalated Cyclophosphamide (PTCy) and Ruxolitinib for Graft-versus-Host Disease (GVHD) Prophylaxis

Inclusion Criteria:

1. History of hematologic malignancy.

2. Must be in remission:

• Acute Leukemia, chronic leukemia, or myelodysplasia/myeloproliferative neoplasm (excluding primary myelofibrosis): No circulating blasts and <5% blasts in thebone marrow.

• Hodgkin and non-Hodgkin lymphomas: Chemo-sensitive disease at time oftransplant

3. Patients must have a related or unrelated peripheral blood stem cell donor that isan 8/8 match at HLA-A, -B, -C and -DRB1 at high resolution using DNA-based typing.Unrelated donors must be willing to donate peripheral blood stem cells and meet NMDPcriteria for donation.

4. Planned reduced intensity conditioning therapy with fludarabine/melphalan, withtotal dose of melphalan of 100-140 mg/m^2 IV or fludarabine/busulfan with total doseof busulfan of 6.4 mg/kg IV.

5. Karnofsky Performance Scale of 60 or greater.

6. Male participants must agree to abstinence or to use of barrier contraception duringthe entire study period.

7. Female participants of childbearing potential will require a negative pregnancy testand should agree to practice two effective methods of contraception during theentire study period.

8. Ability to understand a written informed consent document, and the willingness tosign it.

Exclusion Criteria:

1. Prior allogeneic HCT or Chimeric antigen receptor (CAR) -T cell therapy.

2. Patients with liver dysfunction evidenced by bilirubin ≥2x upper limit normal (ULN),except for a history of Gilbert syndrome.

3. Patients with renal impairment defined by creatinine<2mg/dL.

4. Patients with cardiac dysfunction defined by a left ventricular ejection fraction ≤45%.

5. Patients with pulmonary dysfunction defined by a forced expiratory volume in thefirst second (FEV1) or diffusing capacity for carbon monoxide (DLCO) (corrected forhemoglobin) ≤50% of predicted.

6. Patients with a chronic or active infection requiring systemic treatment during andafter transplant.

7. Presence of other active malignant disease diagnosed within 12 months, except foradequately treated non-melanoma skin cancer, adequately treated melanoma grade 2 orless, or cervical intraepithelial neoplasia. Active malignancy is malignancyreceiving treatment.

8. Pregnant or lactating subjects.