Fludarabine Phosphate, Busulfan, and Anti-Thymocyte Globulin Followed By Donor Peripheral Blood Stem Cell Transplant, Tacrolimus, and Methotrexate in Treating Patients With Myeloid Malignancies

Overview

This phase II trial is studying the side effects and how well giving fludarabine phosphate, busulfan, anti-thymocyte globulin followed by donor peripheral blood stem cell transplant, tacrolimus, and methotrexate works in treating patients with myeloid malignancies. Giving chemotherapy, such as fludarabine phosphate and busulfan, before a donor peripheral blood stem cell transplant helps stop the growth of cancer cells. It may also stop the patient's immune system from rejecting the donor's stem cells. When the healthy stem cells from a donor are infused into the patient they may help the patient's bone marrow make stem cells, red blood cells, white blood cells, and platelets. Sometimes the transplanted cells from a donor can make an immune response against the body's normal cells. Giving anti-thymocyte globulin before transplant and tacrolimus and methotrexate after transplant may stop this from happening.

PRIMARY OBJECTIVE: I. Determine the incidence and severity of acute graft-versus-host disease (GvHD). SECONDARY OBJECTIVES: I. Determine the pharmacokinetics of intravenous (IV) busulfan including interdose variability and evaluation of a limited sampling strategy. II. Determine thymoglobulin (anti-thymocyte globulin) pharmacokinetics. III. Determine the incidence of donor engraftment. IV. Determine system toxicities \>= grade 3 per Common Terminology Criteria for Adverse Events (CTCAE) version (v.) 3. V. Determine the incidence and severity of chronic GvHD. VI. Determine the incidence of non-relapse mortality at day +100 and at 1 year (yr). VII. Determine the incidence of relapse. VIII. Determine relapse-free survival. IX. Determine the incidence of Epstein-Barr virus (EBV) activation. OUTLINE: Patients receive fludarabine phosphate intravenously (IV) over 30 minutes on days -9 to -6, busulfan IV over 3 hours on days -5 to -2, and anti-thymocyte globulin IV over 6 hours on days -3 and -2 and over 4 hours on day -1. Patients undergo allogeneic peripheral blood stem cell (PBSC) transplant on day 0. Patients then receive tacrolimus IV continuously or orally (PO) every 12 hours beginning on day -1 and taper to day 180 and methotrexate IV on days 1, 3, 6, and 11. After completion of study treatment, patients are followed at 1 year.