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THE SUCCESSFUL USE OF INFLIXIMAB IN A PEDIATRIC INTESTINAL TRANSPLANT PATIENT WITH STEROID AND THYMOGLOBULIN RESISTANT LATE INTESTINAL ACUTE REJECTION
E De Greef, D Grant, M De Angelis, K Murch, N Jones, P Pencharz
Hospital for Sick Children, Toronto, Ontario
Aims: Tumor necrosis factor inhibitors have proven useful in inflammatory bowel disease. There is experimental evidence implicating TNF alpha in acute rejection in organ transplantation suggesting that TNF blockade may be beneficial.
Methods: Here we report the successful use of infliximab in a child with refractory acute rejection.
Results: An 8-year old boy who received an isolated intestinal transplant at the age of 3y because of Microvillous Inclusion Disease had several episodes of acute cellular rejection within the first year post transplant which were steroid responsive. For the next 4 years, he had no further episodes of rejection. 5 years post transplant he presented with the clinical appearance of an acute abdomen. Surgical exploration showed a normal appearing bowel. Graft biopsies showed moderate rejection with no evidence of bacterial or viral infection. He was initially treated with pulse steroids and 6 consecutive doses of thymoglobulin. After initial clinical and histological improvement, he relapsed 4 days after his last dose of Thymoglobulin. Two additional doses of thymoglobulin were given with no improvement. Before considering graft removal, a rescue dose of Infliximab (5mg/kg), a monoclonal anti-TNF alpha antibody, was given.Within days, the patient recovered clinically and histologically. Two months after this episode the patient remains well. No further doses of Infliximab were given.
Conclusions: The dramatic clinical improvement in this patient with refractory rejection supports the role of TNF alpha in acute small bowel rejection. Further studies are now warranted to investigate the clinical utility of anti-TNF alpha therapy in the prevention and treatment of acute intestinal rejection.