BACKGROUND: Only a minority of islet transplant recipients maintain insulin independence at 5 years under the Edmonton protocol of immunosuppression. New immunosuppressive strategies are required to improve long-term outcomes. MATERIALS AND METHODS: Three subjects with unstable type 1 diabetes mellitus underwent islet transplantation with alemtuzumab induction and sirolimus-tacrolimus maintenance for 3 months and then sirolimus-mycophenolic acid maintenance thereafter. Follow-up was more than 2 years. Comparison was with 16 historical subjects transplanted under the Miami version of the Edmonton protocol. RESULTS: Insulin independence was achieved in 2 of 3 alemtuzumab and 14 of 16 historical subjects. Those who did not achieve insulin independence only received a single islet infusion. Insulin-independence rates remained unchanged in the alemtuzumab group, but decreased from 14 of 16 (88%) to 6 of 16 (38%) in the historical group over 2 years. Insulin requirements increased in the historical group while remaining stable in the alemtuzumab group. Comparison of functional measures at 3 months suggested better engraftment with alemtuzumab (P=NS). Further comparison of alemtuzumab versus historical groups, up to 24 months, demonstrated significantly better: Mixed meal stimulation index (24 months, 1.0+/-0.08 [n=3] vs. 0.5+/-0.06 pmol/mL [n=6], P<0.01), mixed meal peak C-peptide (24 months, 5.0+/-0.5 [n=3] vs. 3.1+/-0.3 nmol/mL [n=6], P<0.05), HbA1c (24 months, 5.4+/-0.15 [n=3] vs. 6.3+/-0.12 pmol/mL [n=10], P<0.01). Administration of alemtuzumab was well tolerated. There was no increased incidence of infections in alemtuzumab subjects despite profound, prolonged lymphocyte depletion. CONCLUSIONS: Islet transplantation with alemtuzumab induction was well tolerated and resulted in improved short- and long-term outcomes. Further investigation is underway for validation.
BACKGROUND: Only a minority of islet transplant recipients maintain insulin independence at 5 years under the Edmonton protocol of immunosuppression. New immunosuppressive strategies are required to improve long-term outcomes. MATERIALS AND METHODS: Three subjects with unstable type 1 diabetes mellitus underwent islet transplantation with alemtuzumab induction and sirolimus-tacrolimus maintenance for 3 months and then sirolimus-mycophenolic acid maintenance thereafter. Follow-up was more than 2 years. Comparison was with 16 historical subjects transplanted under the Miami version of the Edmonton protocol. RESULTS:Insulin independence was achieved in 2 of 3 alemtuzumab and 14 of 16 historical subjects. Those who did not achieve insulin independence only received a single islet infusion. Insulin-independence rates remained unchanged in the alemtuzumab group, but decreased from 14 of 16 (88%) to 6 of 16 (38%) in the historical group over 2 years. Insulin requirements increased in the historical group while remaining stable in the alemtuzumab group. Comparison of functional measures at 3 months suggested better engraftment with alemtuzumab (P=NS). Further comparison of alemtuzumab versus historical groups, up to 24 months, demonstrated significantly better: Mixed meal stimulation index (24 months, 1.0+/-0.08 [n=3] vs. 0.5+/-0.06 pmol/mL [n=6], P<0.01), mixed meal peak C-peptide (24 months, 5.0+/-0.5 [n=3] vs. 3.1+/-0.3 nmol/mL [n=6], P<0.05), HbA1c (24 months, 5.4+/-0.15 [n=3] vs. 6.3+/-0.12 pmol/mL [n=10], P<0.01). Administration of alemtuzumab was well tolerated. There was no increased incidence of infections in alemtuzumab subjects despite profound, prolonged lymphocyte depletion. CONCLUSIONS: Islet transplantation with alemtuzumab induction was well tolerated and resulted in improved short- and long-term outcomes. Further investigation is underway for validation.
Authors: V Scantlebury; R Shapiro; J Fung; A Tzakis; J McCauley; M Jordan; C Jensen; T Hakala; R Simmons; T E Starzl Journal: Transplant Proc Date: 1991-12 Impact factor: 1.066
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Authors: S Nishida; D M Levi; J I Moon; J R Madariaga; T Kato; G Selvaggi; P Tryphonopoulos; W DeFaria; S Santiago; J Gaynor; D Weppler; E Martinez; P Ruiz; A G Tzakis Journal: Transplant Proc Date: 2006 Jul-Aug Impact factor: 1.066
Authors: A M James Shapiro; Camillo Ricordi; Bernhard J Hering; Hugh Auchincloss; Robert Lindblad; R Paul Robertson; Antonio Secchi; Mathias D Brendel; Thierry Berney; Daniel C Brennan; Enrico Cagliero; Rodolfo Alejandro; Edmond A Ryan; Barbara DiMercurio; Philippe Morel; Kenneth S Polonsky; Jo-Anna Reems; Reinhard G Bretzel; Federico Bertuzzi; Tatiana Froud; Raja Kandaswamy; David E R Sutherland; George Eisenbarth; Miriam Segal; Jutta Preiksaitis; Gregory S Korbutt; Franca B Barton; Lisa Viviano; Vicki Seyfert-Margolis; Jeffrey Bluestone; Jonathan R T Lakey Journal: N Engl J Med Date: 2006-09-28 Impact factor: 91.245
Authors: Edmond A Ryan; Breay W Paty; Peter A Senior; David Bigam; Eman Alfadhli; Norman M Kneteman; Jonathan R T Lakey; A M James Shapiro Journal: Diabetes Date: 2005-07 Impact factor: 9.461
Authors: M Navasa; J Bustamante; C Marroni; E González; H Andreu; E Esmatjes; J C García-Valdecasas; L Grande; I Cirera; A Rimola; J Rodés Journal: J Hepatol Date: 1996-07 Impact factor: 25.083
Authors: M C Lowe; I R Badell; A P Turner; P W Thompson; F V Leopardi; E A Strobert; C P Larsen; A D Kirk Journal: Am J Transplant Date: 2012-12-27 Impact factor: 8.086