Background: Pancreatic islet transplantation (ITx) provides a treatment option for patients with type 1 diabetes (T1D); the clinical results have improved with the introduction of improved immunosuppressive therapies. In Japan, the number of ITxs is small because of donor shortage, and ITx has been performed using the pancreas provided by “marginal” donors, such as donors after cardiac death (DCD) and elderly donors. We report the efficacy and safety of ITx at a single-center in Japan.
Methods: Five C-peptide negative T1D patients with severe hypoglycemic events (SHE) received 2–3 intraportal allogeneic ITxs and received immunosuppressive agents, including antithymocyte globulin, tacrolimus, and mycophenolate mofetil from 2012 to 2019. We assessed sustained islet graft function duration, glycemic control, SHE, and post-transplant complications.
Results: Thirteen islet isolations were performed from two DCD and 11 who were donors after brain death, and 12 preparations met the transplant criteria. The mean age of the donors was 45.5 years, and the cold ischemia time was 387 ± 89 min. Patients received a mean total number of islet equivalent (IEQ)/body weight(kg) of 19,406 IEQ/kg in 2 (n = 3) or 3 (n = 2) ITxs. The portal vein pressure after transplantation was 10.8 ± 4.4 mmHg (change in portal vein pressure was + 2.6 ± 1.7 mmHg). No complications associated with intraportal transplantation, such as liver dysfunction, intraperitoneal hemorrhage, or portal vein embolism was observed. One patient experienced graft rejection at 26 months after the transplantation, with islet graft survival being observed in the other 4 patients (follow-up: 16–54 months). It is noteworthy that these patients had almost normal glycosylated hemoglobin and creatinine levels. Moreover, 2 patients (40%) in the recent ITx group achieved insulin independence, and SHE was resolved in all recent ITx group recipients. As an adverse event, severe leukopenia was temporarily observed in one patient. No infectious complications occurred in any patient.
Conclusion: ITx is considered a highly safe treatment with good clinical results, even in Japan, where there are few donors, and donor conditions are marginal. The future goal is to achieve a higher insulin independent rate and evaluate the long-term outcomes.