T-Guard as Treatment for Steroid Refractory Acute GVHD (BMT CTN 1802)

Inclusion Criteria: 1. Patient must be at least 12.0 years of age at the time of consent. 2. Patient has undergone first allo-HSCT from any donor source using bone marrow, peripheral blood stem cells, or cord blood. Recipients of nonmyeloablative, reduced intensity, and myeloablative conditioning regimens are eligible. 3. Patients diagnosed with SR-aGVHD after allo-HSCT. SR is defined as aGVHD that: * Progressed after 3 days of primary treatment with prednisone (or equivalent) of greater than or equal to 2mg/kg/day * No improvement after 7 days of primary treatment with prednisone (or equivalent) of greater than or equal to 2mg/kg/day. * Patients with visceral (GI and/or liver) plus skin aGVHD at prednisone (or equivalent) initiation with improvement in skin GVHD without any improvement in visceral GVHD after 7 days of primary treatment with prednisone (or equivalent) of greater than or equal to 2mg/kg/day * Previously was treated with prednisone (or equivalent) of greater than or equal to 1mg/kg/day and aGVHD has developed in a previously uninvolved organ system Progression and no improvement are defined in the protocol. Improvement or progression in organs is determined by comparing current organ staging to staging at initiation of prednisone (or equivalent) treatment. Staging is performed per MAGIC criteria. 4. Evidence of myeloid engraftment (e.g., absolute neutrophil count greater than or equal to 0.5 × 10\^9/L for 3 consecutive days if ablative therapy was previously used). Use of growth factor supplementation is allowed. 5. Patients or an impartial witness (in case the patient is capable of providing verbal consent but not capable of signing the informed consent form (ICF)) should have given written informed consent. For patients less than 18 years of age, a written informed consent of the parents or guardian and written assent of the patient will be obtained, per the local requirements. Exclusion Criteria: 1. Patients who have been diagnosed with overlap syndrome, that is, with any concurrent features of cGVHD. 2. Patients requiring any of the following: mechanical ventilation, vasopressor support, or hemodialysis. 3. Patients who have received any systemic treatment, besides steroids, as upfront treatment of aGVHD OR as treatment for SR-aGVHD. 4. Patients who have severe hypoalbuminemia, with an albumin of less than or equal to 1 g/dl. 5. Patients who have a CK level of greater than 5 times the upper limit of normal. 6. Patients with uncontrolled infections. Infections are considered controlled if appropriate therapy has been instituted and, at the time of enrollment, no signs of progression are present. Progression of infection is defined as hemodynamic instability attributable to sepsis, 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. 7. Patients with evidence of relapsed, progressing or persistent malignancy. 8. Patients with evidence of minimal residual disease requiring withdrawal of systemic immune suppression 9. Patients with known hypersensitivity to any of the components murine monoclonal antibodies (mAb) or Recombinant Ricin Toxin A-chain (RTA). 10. Patients who have received more than one allo-HSCT. 11. Patients with known human immunodeficiency virus infection. 12. Female patients who are pregnant, breast feeding, or, if sexually active and of childbearing potential, unwilling to use effective birth control from start of treatment until 30 days after the last infusion of T-Guard. 13. Male patients who are, if sexually active and with a female partner of childbearing potential, unwilling to use effective birth control from start of treatment until 65 days after the last infusion of T-Guard. 14. Patients with any condition that would, in the investigator's judgment, interfere with full participation in the study, including administration of study drug and attending required study visits; pose a significant risk to the patient; or interfere with interpretation of study data. 15. Patients whose decision to participate might be unduly influenced by perceived expectation of gain or harm by participation, such as patients in detention due to official or legal order.