Oral Communications 11
23.2 - High doses of Everolimus as induction treatment improve graft function in islet allotransplantation
Presenter: Federico, Bertuzzi, Milan, Italy
Authors: Federico Bertuzzi1,2,3,4, Mario Marazzi1,2,3,4, Antonio Gaetano Rampoldi1,2,3,4, Andrea De Gasperi1,2,3,4, Luciano De Carlis1,2,3,4, Barbara Antonioli1,2,3,4, Enrico Minetti1,2,3,4, Livio Luzi1,2,3,4, Matteo Bonomo1,2,3,4, Giacomo Colussi1,2,3,4
High doses of Everolimus as induction treatment improve graft function in islet allotransplantation
Federico Bertuzzi1,2,3,4, Mario Marazzi1,2,3,4, Antonio Gaetano Rampoldi1,2,3,4, Andrea De Gasperi1,2,3,4, Luciano De Carlis1,2,3,4, Barbara Antonioli1,2,3,4, Enrico Minetti1,2,3,4, Livio Luzi1,2,3,4, Matteo Bonomo1,2,3,4, Giacomo Colussi1,2,3,4
1Niguarda Hospital, Milan, Italy; 2IRCCS Policlinico San Donato, Milan, Italy; 3Careggi Hospital, Florence, Italy; 4University of Milan, Milan, Italy
Although largely improved in the last years, graft function is still variable in human islet transplantation. Early islet inflammatory reaction in the site of islet implant was suggested to reduce islet engraftment and to impair early and long term graft function. MTOR inhibitors seem to have anti-inflammatory effects.
Human islet transplantation was performed in 8 patients affected by type 1 diabetes mellitus . 7 patients were affected by brittle diabetes, 1 patient had been previously transplanted with kidney pancreas transplantation and had lost pancreas for rejection. Recipient body weight was 67kg (range 49-86). Pre transplant c-peptide was <0.5ng/ml. Patients were transplanted with 9.700 +/-3.200 IE/kg b.w.
Immunosuppression consists on an induction treatment with polyclonal ALG (1mg/kg/day for 5 days) in the case of the first transplant, 20mg Basiliximab in the case of islet after kidney recipient or in the case of a second islet transplant (in 4 patients). 3mg of Everolimus was added to the induction treatment 12 hours and 1 hour before islet transplantation. Maintenance immunosuppression treatment consists of micofenolate and tacrolimus according to standard protocol.
No primary non function was observed. 6 patients out 8 are still insulin independence after the last islet transplantation (36, 28, 27, 24, 3, 1 months follow up). In onepatient a recurrence of autoimmune reactivity was observed with the loss of engrafted beta cell mass; a second patient refused a second islet transplantation and lost graft function 1 year after transplantation.
In this pilot study, in a small cohort of patients a refinement of immunosuppression induction treatment improved the overall islet graft function.