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Presenter: David, Thompson, Vancouver, Canada
Authors: Thompson D., Ao Z., Meloche M., Shapiro J., Keown P., Paty B., Fung M., Ho S., Almehthel M., Kondi J., Meneilly G., Kozak S., Tong S., Trinh M., Warnock G.
ISLET AND PANCREAS TRANSPLANTATION I
D.M. Thompson1, Z. Ao2, M. Meloche3, J. Shapiro4, P.A. Keown5, B. Paty1, M. Fung1, S. Ho6, M. Almehthel7, J. Kondi1, G. Meneilly1, S.E. Kozak1, S. Tong1, M. Trinh4, G. Warnock3
1Medicine, Vancouver General Hospital, Vancouver/CANADA, 2Department Of Surgery, University Of British Columbia, Human Islet Transplant Laboratory, Vancouver/CANADA, 3Surgery, Vancouver General Hospital, Vancouver/CANADA, 4, Vancouver General Hospital, Vancouver/CANADA, 5Medicine, University of British Columbia, Vancouver/CANADA, 6Radiology, Vancouver General Hospital, Vancouver/CANADA, 7Medicine, University of British Columbia, Vancouver/BC/CANADA
Body:
Introduction: The factors responsible for determining the reduction in insulin dose following an islet infusion are poorly understood. Methods: The British Columbia Islet Transplant program has performed 81 islet infusions in 32 patients between March 2003 and February 2010. Eligible subjects were 20 – 65 years of age with > 5yrs diabetes, c-peptide negative and had retinopathy and mild nephropathy. Islets were isolated using a standard protocol and infused percutaneously into the portal vein. Immunosuppression consisted of ATG induction followed by sirolimus (2) or mycophenolate (30) and tacrolimus. Subsequent islet infusions used basiliximab for induction. Repeat islet infusions are offered until a subject has received > 12,000 IE/kg and a subject receives up to four infusions to try and achieve or maintain insulin independence. One clinically meaningful measure of the success of an islet infusion is reduction in pre-infusion insulin dose. We have found that the maximum insulin reduction occurs by 8-12 weeks after an infusion, presumably reflecting successful islet engraftment. Results: We define a good response as a reduction of >80% of pre-infusion insulin dose, fair as a 25-80% reduction and poor as a < 25% reduction. Of the 81 infusions, 14 were separated by < 8 weeks and these 14 are analyzed as a single infusion. A good response was obtained in 35/67 infusions (52%), fair in 25 (37%) and poor in 7 (11%). Once stopping insulin, 36% remained insulin free for < 12 months, 30% for 12-24 months, 15% for 25-36 months, 15% for 37-48 months and 18% for > 48 months. Overall, 22 of 32 subjects stopped insulin for at least 3 months and 10 remain insulin independent. The c-peptide level at 8-12 weeks is significantly higher for good (511 pmol/L ± 235) than for fair (281 ± 188) or poor (140 ± 130) outcomes (p < .001). We found recipient blood groups A, B or AB had a significantly greater chance of a good outcome than recipient blood group O (p < .05). The average size of infused islets was significantly smaller for good (2.0 ± 0.6 IE/islet ) or fair (1.9 ± 0.5) than for poor (2.8 ± 0.9) outcomes (p < .01). Recipient factors that did not correlate with outcome included age, weight, BMI or pre-infusion insulin dose. Islet factors that did not correlate included donor age, cold ischemia duration and the purity or volume of the islet infusion. In contrast to some programs, we did not find that the number of islets infused (good 542857 ± 261017 IE, 8434 ± 3815 IE/kg, fair (623559 ± 295404 IE, 9038 ± 4470 IE/kg, poor (601859 ± 221127 IE, 8391 ± 2648 IE/kg) or the total number of islets (good 1095297 ± 335830 IE, 16978 ± 5262 IE/kg, fair (925333 ± 457284 IE, 13242 ± 6233 IE/kg, poor (919369 ± 407504 IE, 13439 ± 7423 IE/kg) a subject has received predicted the outcome. Conclusion: We conclude that additional unidentified factors are involved in determining the success of an islet transplant in reducing insulin requirements.
Disclosure: All authors have declared no conflicts of interest.
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