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

Eligibility 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 the bone marrow.
• * Hodgkin and non-Hodgkin lymphomas: Chemo-sensitive disease at time of transplant
• 3. Patients must have a related or unrelated peripheral blood stem cell donor that is an 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 NMDP criteria for donation.
• 4. Planned reduced intensity conditioning therapy with fludarabine/melphalan, with total dose of melphalan of 100-140 mg/m\^2 IV or fludarabine/busulfan with total dose of 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 during the entire study period.
• 7. Female participants of childbearing potential will require a negative pregnancy test and should agree to practice two effective methods of contraception during the entire study period.
• 8. Ability to understand a written informed consent document, and the willingness to sign it.
• 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 the first second (FEV1) or diffusing capacity for carbon monoxide (DLCO) (corrected for hemoglobin) ≤50% of predicted.
• 6. Patients with a chronic or active infection requiring systemic treatment during and after transplant.
• 7. Presence of other active malignant disease diagnosed within 12 months, except for adequately treated non-melanoma skin cancer, adequately treated melanoma grade 2 or less, or cervical intraepithelial neoplasia. Active malignancy is malignancy receiving treatment.
• 8. Pregnant or lactating subjects.