Low Dose Irradiation for Small Bowel Transplant
Condition: Irreversible Intestinal Failure; Allograft Rejection
MeSH terms: Intestinal Failure
Study type: Observational

Summary: 
      The specific aims of this study is to improve short and long-term patient and graft survival,
      to reduce the incidence and severity of allograft rejection, to reduce the incidence of
      infection and to reduce and/or eventually eliminate the need for long-term immunosuppression.
    

Detailed description: 
      The rationale behind this study involves the need to better manage rejection in the
      intestinal allograft recipient. Although tacrolimus based immunosuppression has made
      intestinal transplantation feasible, the requisite need for chronic high dose
      immunosuppression in order to control rejection has inhibited the wide spread clinical use
      and practicality of intestinal/multivisceral transplantation. The measures needed to prevent
      graft loss have frequently resulted in lethal infections, the leading cause of death. This
      trial is significant for determining if this new strategy of allograft immune-modulation with
      low dose ex-vivo irradiation and simultaneous done bone marrow cell infusion will favorably
      affect short and long term outcomes by reducing the risk of allograft rejection.

      This trial is offered to all patients with irreversible intestinal failure who must undergo
      intestinal, combined liver-intestinal, and multivisceral transplantation at the University of
      Pittsburgh Medical Center. Patients are recruited through the referral system and no cold
      calling is carried out. Patient confidentiality is maintained by the use of codes to identify
      the study participants. All data is stored in a locked filing cabinets as a means to protect
      participants against a breach of confidentiality. This trial involves ex-vivo low dose
      irradiation of the intestinal allograft with or without adjunct donor bone marrow cell
      infusion. An intravenous bone marrow cell infusion is prepared form the thoracolumbar
      vertebral bodies harvested from cadaveric donors. Control subjects will be those who refuse
      to be enrolled in the study or those for whom donor bone marrow is not available. All
      patients will be treated perioperatively with thymoglobulin, a rabbit polyclonal
      anti-lymphocyte globulin at a dose of 5-10 mg/kg. Tacrolimus will be given in a standard
      fashion and from the outset as a single monotherapeutic agent to prevent early allograft
      rejection and promote graft acceptance. All patients will be monitored for rejection, graft
      function, opportunistic infections and GVHD. Surveillance endoscopy with guided mucosal
      biopsies will be obtained according to the standard protocol. Attention will be paid for any
      clinicopathologic changes suggestive of acute or chronic irradiation injuries.

      The study closed for enrollment as of 9/30/03.
    

Intervention name(s): Reduce the risk of allograft rejection
Intervention type(s): Procedure
Time perspective: Prospective
Keywords: Intestinal transplant; Bone marrow; Irradiation of allograft