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Abstract of First Islet Study - December 2006
Islet Cell Transplantation Using Surgical Cannulation of the Portal Vein Followed by Delayed Conversion to a MMF and Tacrolimus Immunosuppressive Regimen
MR Rigby 1,2 KE Kokko 1,3 MH Sears 1, E Holbrook 1, K Cardona 1, ZL Milas 1, S Raja 1, J Cano 1, PH Bowen 3, TC Pearson 1 and CP Larsen 1. 1Surgery; 2Pediatrics, and 3Medicine, Emory University, Atlanta, GA.
Body: Islet cell transplantation using a glucocorticoid-free immunosuppressive regimen can render up to 70% of patients with T1DM insulin-independent at 1 year; yet, only 10% of patients remain insulin-free at 5 years. In addition to poor graft survival, there are risks and side effects of both transhepatic islet delivery and immunosuppressive medications. We report the safety and efficacy of a surgical approach to achieve vascular access for islet delivery and the conversion to a mycophenolate mofetil (MMF)- and tacrolimus (tac)-based immunosuppression regimen.
Since 2003, we have conducted 15 islet transplants on 8 patients with T1DM and severe hypoglycemic unawareness. Patient characteristics include: mean age 45yrs, length of diabetes 29yrs, BMI 23kg/m2, and 6/8 female. Patients received an average of 1.8 transplants and 14.6K IEQ/kg. All received intraportal transplants using a catheter placed into a mesenteric vein under direct visualization following mini-laparotomy. No portal hypertension, portal vein thrombosis or intra-abdominal bleeding was observed. All received daclizumab induction and tac + sirolimus immunosuppression. Six of 8 patients (75%) achieved insulin independence; all 6 were insulin-free 1 year following completion transplant. All patients experienced mouth ulcerations, gi complaints, elevated aminotransferases and leukopenia. One patient was hospitalized for dehydration, 1 for appendicitis, and 3 required surgical repair of abdominal hernias. All patients were transitioned to MMF + tac maintenance therapy. At the time of conversion 5 were insulin-free and 3 were c-peptide+ requiring insulin. Patients have been maintained on this regimen from 4 to 25 months. During this time there has been a reduction in adverse events and no serious adverse events. Following conversion, 1 patient has lost insulin independence and 1 has experienced graft failure.
Using a mini-laparotomy to access the portal system for islet delivery and transitioning to MMF + tac immunosuppressive regimen appears to be safe and well tolerated. Further studies are required to assess how these alternatives impact islet engraftment and survival compared to other approaches. Such modifications may lead to fewer risks and improved insulin independence, assisting the evolution of this approach to be an acceptable therapy for all with T1DM.
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