Acute Graft-versus-Host Disease Treatment (BMT CTN 0802)

Inclusion Criteria: * Acute GVHD developing after allogeneic hematopoietic stem cell transplant using either bone marrow, peripheral blood stem cells or cord blood. Recipients of non-myeloablative and myeloablative transplants are eligible. * Acute GVHD after planned donor lymphocyte infusion or planned T cell add back are eligible. * De novo acute GVHD requiring systemic therapy. GVHD is defined as the presence of skin rash and/or persistent nausea, vomiting, and/or diarrhea and/or cholestasis presenting in a context in which acute GVHD is likely to occur and where other etiologies such as drug rash, enteric infection, or hepatotoxic syndromes are unlikely or have been ruled out. Note that patients with stage I and II skin only (overall grade I) or isolated upper gastrointestinal (GI) involvement are eligible if the treating physician deems that systemic high-dose corticosteroid treatment is indicated. * The patient must have had no previous systemic immune suppressive therapy for treatment of acute GVHD except for a maximum 72 hours of prior corticosteroid therapy at \>0.5mg/kg methylprednisolone or equivalent after the onset of acute GVHD. * Clinical status at enrollment to allow tapering of steroids to not less than 0.25 mg/kg/day prednisone (0.2 mg/kg/day methylprednisolone) at Day 28 of therapy. * Absolute neutrophil count (ANC) greater than 500/µL. * Written informed consent and/or assent from patient, parent or guardian. * Documentation that the assent document and education materials have been provided to, and reviewed with, patients between the ages of 7 and 17. * Patients of all ages are eligible. * Biopsy confirmation of GVHD is recommended, but not required. Enrollment should not be delayed for biopsy or pathology results unless these are to be used to decide about whether to treat for GVHD. Exclusion Criteria: * Patients receiving mycophenolate mofetil or mycophenolic acid (Myfortic) within seven days of screening for enrollment. * Patients with uncontrolled infections will be excluded. If a bacterial or viral infection is present, patients must be receiving definitive therapy and have no signs of progressing infection for 72 hours prior to enrollment. If a fungal infection is present, patients must be receiving definitive systemic anti-fungal therapy and have no signs of progressing infection for 1 week prior to enrollment. Progressing infection is defined as hemodynamic instability attributable to sepsis or new symptoms, worsening physical signs or radiographic findings attributable to infection. Persisting fever without other signs or symptoms will not be interpreted as progressing infection. * Relapsed/persistent malignancy requiring rapid immune suppression withdrawal. * Patients with GVHD after an unplanned Donor Lymphocyte Infusion (DLI), i.e., DLI that was not part of their original transplant therapy plan, or DLI given for treatment of persistent or recurrent malignancy after transplantation. * Patients unlikely to be available at the transplantation center on Day 28 and 56 of therapy. * A clinical syndrome resembling de novo chronic GVHD developing at any time after allotransplantation. * Patients receiving other drugs for the treatment of GVHD. * Patients receiving methylprednisolone \> 0.5 mg/kg/day (or 0.6 mg/kg/day prednisone) within 7 days before the onset of acute GVHD. If steroid therapy has been administered for treatment of a non-GVHD related condition and tapered to ≤ 0.5 mg/kg/day methylprednisolone (0.6 mg/kg/day prednisone) for seven or more days before the onset of acute GVHD, the patient is eligible. * Patients who are pregnant, breast feeding, or, if sexually active, unwilling to use effective birth control for the duration of the study. Available evidence and/or expert consensus is inconclusive or is inadequate for determining infant risk when used during breastfeeding, therefore breast feeding patients are not eligible. * Adults unable to provide informed consent. * Patients on dialysis. * Patients with severe hepatic Veno-Occlusive Disease (VOD) or sinusoidal obstruction syndrome who in the judgement of the treating physician are not expected to have normalized bilirubin by Day 56 after enrollment. * Patients with a history of intolerance/allergy to MMF.