Inclusion Criteria:

1. Prior allogeneic hematopoietic stem cell transplant using either bone marrow, peripheral blood stem cells or cord blood. Recipients of non-myeloablative transplants are also eligible.
2. De novo Grade B-D acute GVHD diagnosed within 48 hours of diagnosis. GVHD is defined as the presence of skin rash and/or persistent nausea, vomiting, and/or diarrhea and/or cholestasis as the clinical criteria of GVHD when present in the right clinical setting and not directly attributable to other etiologies (such as drug rash, enteric infection, or hepatotoxic syndromes). The patient must have had no previous systemic immune suppressive therapy given for treatment of acute GVHD except for a maximum of 48 hours of prior corticosteroid therapy (> 1 mg/kg/day methylprednisolone).
3. No previous immune suppressive therapy given for treatment of acute GVHD except for a maximum 48 hours of prior corticosteroid therapy >/= 1 mg/kg/day methylprednisolone.
4. Clinical status at enrollment to allow tapering of steroids to no less than 0.6 mg/kg/day methylprednisolone (0.75 mg/kg/day prednisone) at Day 28 of therapy.
5. Absolute neutrophil count (ANC) greater than 500/microL.
6. Estimated creatinine clearance greater than 30 mL/minute. At our institution this will be calculated with the Cockcroft-Gault equation.
7. Written informed consent from patient, parent or guardian.
8. Documentation that the assent document and education materials have been provided to, and reviewed with, patients under the age of 18.
9. Greater than or equal to 6years of age at the time of enrollment.
10. DLI (donor lymphocyte infusion) as part of the original transplant therapy plan.

Exclusion Criteria:

1. ONTAK, pentostatin, or etanercept given within 7 days of enrollment.
2. Active uncontrolled infection.
3. GVHD developing after an unscheduled donor lymphocyte infusion, not part of the original transplant therapy plan, given for treatment of persistent or recurrent malignancy after transplantation.
4. Patients receiving methylprednisolone > 0.5 mg/kg/day (or 0.6 mg/kg/day prednisone) within 7 days of onset of acute GVHD. If steroid therapy has been administered for a non-GVHD related condition and tapered to < 0.5 mg/kg/day methylprednisolone (or 0.6 mg/kg/day prednisone) for seven or more days prior to the onset of acute GVHD, the patient is eligible.
5. Patients unlikely to be available at the transplantation center on Day 28 and 56 of therapy.
6. A clinical syndrome resembling de novo chronic GVHD developing at any time after allotransplantation. See Chapter 2 of the BMT CTN Manual of Procedures for details of de novo clinical GVHD.
7. Other investigational therapeutics for GVHD within 30 days, including agents used for GVHD prophylaxis.
8. Patients who are pregnant, breast feeding, or, if sexually active, unwilling to use effective birth control for the duration of the study.
9. Adults unable to provide informed consent.
10. Patients with a history of intolerance to any of the study drugs.
11. Patients with isolated limited skin (stage I) as the sole manifestation of acute GVHD.