Donor Stem Cell Transplant With Treosulfan, Fludarabine, and Total-Body Irradiation for the Treatment of Hematological Malignancies

OUTLINE: Patients are assigned to 1 of 2 arms. ARM A (HIGH DOSE TREOSULFAN): Patients receive high dose treosulfan intravenously (IV) over 120 minutes on days -6 to -4 and fludarabine IV over 60 minutes on days -6 to -2. Patients then undergo total-body irradiation on day -1 and allogeneic hematopoietic stem cell transplantation on day 0. Patients then receive cyclophosphamide IV over 1-2 hours on days 3-4. Beginning on day 5, patients receive cyclosporine IV twice daily (BID) or three times daily (TID) over 1-2 hours or orally (PO) (after 3 months, in the absence of GVHD, cyclosporine tapering will start by 5-10% per week, until drug withdrawal at 6 months post-transplant). Beginning on day 5, patients also receive mycophenolate sodium PO TID or mycophenolate mofetil IV or PO TID until day 35 (may be continued if active GVHD is present). Beginning on day 5, patients also receive filgrastim until the absolute neutrophil count is \> 1,000/uL for 3 consecutive days. Additionally, patients undergo bone marrow aspiration and biopsy, and echocardiography at baseline and blood sample collection and computed tomography (CT) or positron emission tomography (PET)/CT on study. ARM B (LOW DOSE TREOSULFAN): Patients receive low dose treosulfan IV over 120 minutes on days -6 to -4 and fludarabine IV over 60 minutes on days -6 to -2. Patients then undergo total-body irradiation and allogeneic hematopoietic stem cell transplantation, and receive cyclophosphamide, cyclosporine, mycophenolate sodium or mycophenolate mofetil, and filgrastim as in Arm A. Additionally, patients undergo bone marrow aspiration and biopsy, and echocardiography at baseline and blood sample collection and CT or PET/CT on study. After completion of transplant, patients are followed up at 28, 56, 84, 365, and 730 days.