246 Islet allotransplantation : single centre experience 1989-2015
Monday November 16, 2015 from 11:00 to 12:30
Plenary Room 1

Islet allotransplantation : single centre experience 1989-2015

Paola Maffi1, Lorenzo Piemonti MD2, Rita Nano Biol2, Paola Magistretti Biol2, Raffaella Melzi Biol2, Alessia Mercalli Biol2, Massimo Venturini MD3, Carlo Socci MD4, Antonio Secchi MD5.

1Internal Medicine and Transplant Unit - Diabetes Research Institute, Scientific Institute Ospedale San Raffaele, Milan, Italy; 2Beta Cell Biology Unit - Diabetes Research Institute, Scientific Institute Ospedale San Raffaele, Milan, Italy; 3Department of Radiology, Scientific Institute Ospedale San Raffaele, Milan, Italy; 4Department of Surgery, Scientific Institute Ospedale San Raffaele, Milan, Italy; 5Internal Medicine and Transplant Unit - Vita Salute University, Scientific Institute Ospedale San Raffaele, Milan, Italy

This study is a retrospective analysis of overall experience on islet allotransplantation  developed at San Raffaele Scientific Institute-Milan, starting since 1989.

Following Islet Transplantations were performed: Islet Transplant Alone (ITA), Islet Transplant After or simultaneous with  Kidney (IAK). 137 patients with type 1 diabetes underwent islet transplant: seventy three patients received ITA, sixty four patients received IAK. Total infusions were 214, 129 in ITA (mean 1.8+0.7 infusions / patient), 85 in IAK (mean 1.3 + 0.5 infusions / patient). The islets were isolated with the Ricordi method, locally modified as previously described, and they were infused under local anesthesia and ultrasound guide in the portal vein. ITA received different immunosuppressive protocol: standard Edmonton (forty four patients, ten among them were randomized to CXCL8 inhibitor- reparixin protocol),  rapamycin pre transplant plus Edmonton (ten patients), Edmonton plus anti TNF alfa (eight patients), ATG induction and calcyneurin free protocol (ten pateints), ATG induction and mycophenolate mofetil associated with tacrolimus or sirolimus (nine patients).  IAK  immunosuppression was based on maintenance of therapy previously established for kidney, azathioprine plus cyclosporine, mycophenolate mofetil plus tacrolimus.
While the analysis is underway, four ITA patients are waiting for 2nd infusion and they were not included in the results. Patients receiving islet mass >10,000 IEq/kg were 37/69 ITA and 24/64 (37.5%) IAK.   2nd infusion was performed after mean time of 136 + 102 days in ITA and 51 + 63 days in IAK.  Longest time of follow-up, calculated as the time of function in terms of c-peptide secretion > 0.3 ng/mL, was 131 months  in ITA  and 180 months in IAK.  Primary non function (no evidence of c-peptide secretion) was never observed. Early function exhaustion (c-peptide < 0.3 ng/mL within 5 weeks since 1st infusion) was observed in nine ITA (one patient  hyperimmune because of previous failed pancreas transplant included) and in three IAK (first patient transplanted in 1989 included). Partial function (c-peptide > 0.3 ng/mL,  reduction in exogenous  insulin dosage > 30% of pre islet transplant) was observed in thirty six ITA and forty IAK. Insulin independence, for more than 1 month, was observed in 28/69 ITA and 21/64 IAK. The longest duration of insulin independence was 105 months in ITA, while 65 months in IAK (this patient died insulin free because of heart  disease). Severe adverse events  related to the infusion procedure were observed in two cases of ITA and one case of SIK: patients underwent laparoscopy immediately after infusion because of peritoneal hemorrhage. Two ITA recipients intentionally stopped immunosuppression since inadequate compliance, even though one patient was insulin free. Post- transplant lymphoproliferative diseases were not observed in ITA recipients, while three cases  occurred in IAK.  Malignancies, breast  carcinoma and squamous cell carcinoma were observed in one case, in one ITA recipient, 2 years after immunosuppression withdrawal;  in two cases of IAK were observed one sarcoma, one squamous cell carcinoma. No death related to islet transplant were observed in both group.
These results confirm that islet transplantation is a feasible procedure, with many chances to succeed also for a long time (more than 9 years), that is not burned  by major related complications .

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