The investigator propose to employ two preparative regimens based on the underlying hematological malignancy. For hematological malignancies of the lymphoid lineage we will use a standard preparative regimen consisting of Total Body Irradiation and cyclophosphamide (TBI/Cy), unless TBI is contraindicated. For myeloid malignancies we will use thiotepa, busulfan, and fludarabine (TBF), a preparative regimen that has been associated with a reduced risk of relapse and trend for improved survival with comparable NRM in comparison to busulfan and cyclophosphamide (BuCy), our current regimen. All HCT recipients will receive cyclosporine in combination with methotrexate and ruxolitinib as GVHD prophylaxis. Recipients of MUD HCT will receive rATG for additional immunosuppression as is standard for unrelated donor transplants
The participants are being asked to take part in this clinical trial because the participant have a lymphoid or myeloid based cancer diagnosis that requires a bone marrow transplant.~Primary Objectives~To estimate the incidence of severe acute GVHD (saGVHD) using a prophylaxis regimen with no calcineurin inhibitors after day +60 post first allogeneic Human Leukocyte antigen (HLA)-matched sibling or unrelated donor HCT for hematological malignancies.~Secondary objective~Determine the cumulative incidence of relapse, NRM, chronic GVHD, and OS in study participants at one year post-transplant.~Exploratory objectives~To evaluate the pharmacokinetic/pharmacodynamic (PK/PD) profiles of ruxolitinib, fludarabine, and rATG.~To assess immune reconstitution in study participants within the first year post-HCT.