Mismatched Transplantation Using High-dose Post-transplant Cyclophosphamide

The Study Treatment: Cyclophosphamide is designed to interfere with the multiplication of cancer cells, which may slow or stop their growth and spread throughout the body. This may cause the cancer cells to die. In this study, researchers want to learn if cyclophosphamide can help to prevent graft-versus-host disease (GVHD -- when transplanted immune tissue, such as white blood cells, attacks the tissues of the recipient's body). Melphalan, thiotepa, and fludarabine are commonly used in combination with a stem cell transplant. Study Treatment Administration: If you are found to be eligible to take part in this study, you will receive chemotherapy for 6 days: * You will receive melphalan by vein over 30 minutes on Day -8 (8 days before the transplant). * You will receive thiotepa by vein over 4 hours on Day -7. * You will receive fludarabine by vein over 1 hour on Days -6, -5, -4, and -3. If thiotepa is not available, you will receive melphalan by vein over 30 minutes on Day -6 and fludarabine by vein over 1 hour on Days -5, -4, -3, and -2. You will receive total body irradiation (TBI) on Day -1. On Day 0, you will receive the donor's stem cells by vein. This may last anywhere from 15 minutes to several hours. On Days 3 and 4, you will receive cyclophosphamide by vein over 3 hours. You will also receive mesna by vein over 30 minutes every 4 hours for a total of 10 mesna doses on Days 3 and 4. Mesna is given to lower the risk of side effects to the bladder. Starting on Day 5, you will receive tacrolimus and mycophenolate mofetil (MMF) to help lower the risk of GVHD. Tacrolimus will be given by vein as a continuous infusion for about 2 weeks. After the 2 weeks of taking tacrolimus by vein, you will take tacrolimus by mouth as a pill for at least 3 months. MMF will be given by mouth, 3 times a day, usually until Day 35. Starting on Day 7, you will receive filgrastim (G-CSF) once a day as an injection under the skin, until your blood cell counts reach a high enough level. Depending on the type of disease that you have, your doctor may decide to give you rituximab by vein over several hours on Days -13, -6, 1, and 8. Rituximab is given to help the body get rid of abnormal white blood cells. Length of Study Participation: You will be in the hospital for about 4 weeks after the transplant. You will be taken off study if the disease gets worse. The study drugs will be stopped if intolerable side effects occur. Follow-Up Visits: You will be asked to stay close enough to Houston to be able to come back for any visits for at least 100 days after the transplant. At 1, 3, 6, and 12 months after the transplant, the following tests and procedures will be performed: * You will have a physical exam. * Blood (about 4 tablespoons) will be drawn for routine tests. * You will have a bone marrow biopsy/aspirate to check the status of the disease. If you have lymphoma or aplastic anemia, you may have a bone marrow biopsy/aspirate at 3, 6, and 12 months, if your doctor thinks it is needed. * Blood (about 4 tablespoons) will be drawn to measure tumor cells and to predict graft failure and/or relapse. * You may have urine collected and/or scans performed such as x-rays, CT scans, and/or a positron emission tomography (PET) scan. These scans and urine tests would only be done if the study doctor thinks they are needed to check the status of the disease. * Blood (about 4 tablespoons) will be drawn to check your immune system. If you have AML, at 2 months after the transplant, blood (about 4 tablespoons) will be drawn to check your immune system. If you have MM, you will have a bone survey once a year. If the study doctor thinks it is needed based on side effects you may be having, additional follow-up tests will be performed. You may be contacted by phone 1-2 times a year to ask about the status of the disease. These calls will take about 10 minutes to complete. This is an investigational study. All of the drugs used in this study are commercially available and FDA approved. However, it is investigational to give high-dose cyclophosphamide for preventing GVHD that may occur after a stem cell transplant from a tissue-mismatched donor. Up to 337 patients will take part in this study. All will be enrolled at MD Anderson.