Phase II Trial of Natalizumab + Prednisone for Initial Therapy of Acute GI GVHD

Inclusion Criteria: * Participants must meet the following criteria on screening examination to be eligible to participate in the study: * Participants must have acute Graft-Versus-Host Disease (GVHD) of the lower gastrointestinal tract as defined by the clinical impression of the treating physician, requiring systemic treatment. Minimum criteria for GI GVHD includes diarrhea of greater than 500 mL/day. Biopsy of the GI tract is required for study entry and must confirm the diagnosis of acute GVHD. Stool samples to rule out infectious causes of diarrhea, including norovirus, Clostridium difficile and other clinically indicated infections must also be negative. Eligibility includes: * Acute GVHD developing after allogeneic hematopoietic stem cell transplantation (HSCT) using bone marrow, peripheral blood stem cells, or umbilical cord blood. Recipients of non-myeloablative, reduced intensity and myeloablative transplants are eligible. * Patients who develop acute GVHD after donor lymphocyte infusion (DLI) are eligible. * There is no specified time window after day 0 of transplant as acute GVHD is only defined by clinical manifestations. * Patients must have experienced neutrophil engraftment after HSCT as defined by absolute neutrophil counts ≥ 500 / µL × 3 consecutive measurements. Absolute neutrophil count (ANC) should be calculated using the standard formula (Neut + Bands)(WBC × 101). * The presence of hepatic, upper GI and/or cutaneous acute GVHD is permitted. * Steroids can be started up to 7 days prior to the administration of natalizumab. * Age ≥ 18 * Ability to understand and the willingness to sign a written informed consent document. Exclusion Criteria * Participants who exhibit any of the following conditions at screening will not be eligible for admission into the study: * Patients with the entity of Acute/Chronic GVHD overlap syndromes. * Requiring mechanical ventilation * Vasopressor requirement * Concurrent hepatic veno-occlusive disease (VOD) based on clinical examination * Karnofsky performance status \< 30 * Participants may not be receiving any other study agents for at least 7 days prior to enrollment * Prior use of natalizumab for any reason is not allowed * Pregnant women are excluded from this study because of the potential teratogenic effects of natalizumab. Because natalizumab enters breast milk, and the effect is unknown in infants, breastfeeding should be discontinued if the mother is treated with natalizumab.