2013 - ISBTS 2013 Symposium
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Posters and Exhibition
15.69 - Infliximab for Management of Persistent Inflammation, Ulceration and Acute Cellular Rejection in Paediatric Intestinal Transplant Recipients.
Presenter: Marie, O'meara, , United Kingdom
Authors: Marie O'Meara1,2, Anil Dhawan1, Babu Vadamalayan1, Jonathan Hind1
Infliximab for Management of Persistent Inflammation, Ulceration and Acute Cellular Rejection in Paediatric Intestinal Transplant Recipients.
Marie O'Meara1,2, Anil Dhawan1, Babu Vadamalayan1, Jonathan Hind1
1Paediatric Liver, GI and Nutrition Centre, King's College Hospital NHS Foundation Trust, London, United Kingdom; 2Department of Pharmacy, King’s College Hospital NHS Foundation , London, United Kingdom
Background
TNFα upregulation correlates with severity of acute cellular rejection (ACR) in animal models of intestinal transplant (IT). Conventional immunosuppressive agents do not effectively suppress TNFα. Infliximab had been used for treatment of ACR in small numbers of patients post IT. We describe our experience of infliximab as rescue therapy in persistent ulceration and inflammation with/without ACR post isolated small bowel transplant (ISBT).
Patients & Methods
3 patients, underlying diagnoses gastroschisis (2) and chronic intestinal pseudo-obstruction (1), received an ISBT at 4, 5 and 16 years of age respectively. Immunosupression was Basiliximab induction; Tacrolimus and prednisolone maintenance. Two patients had histological features of acute cellular rejection at 6 and 28 months post IT. One was steroid resistant but responded to Anti-Thymocyte globulin. Infliximab was commenced at 7, 11 and 29 months post transplant for pyrexia and increased stoma losses. There was persistent graft mucosal ulceration and biopsy proven inflammation but no or minimal crypt apoptosis. Infectious aetiology was excluded. Patients received 2, 7 and 7 doses of infliximab respectively at 5mg/kg, increasing to 10mg/kg for 2 doses in the 2 patients on longer-term treatment.
Results
Infliximab was well tolerated. Symptoms and histology improved in all patients.
The histology of the patient who received only 2 doses showed well-preserved mucosal architecture without inflammation or apoptosis after the second dose and treatment was discontinued.
In the remaining two patients, follow up is 10months post initiation. One patient has borderline/mild rejection intermittently on histology but continues to improve clinically. The other patient remains clinically well but the graft, though improved, continues to show ulceration. Infliximab trough levels were sub-optimal in this patient and the dose was subsequently increased.
Conclusion
Our initial results indicate that Infliximab may be a promising agent in the treatment of inflammation, ulcers and ACR in this patient group. The optimum dose, level and treatment duration is not yet established. Further prospective work is indicated to confirm efficacy and safety.
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