Islet transplantation with alemtuzumab induction and calcineurin-free maintenance immunosuppression results in improved short- and long-term outcomes

Tatiana Froud, David A. Baidal, Raquel Faradji, Pablo Cure, Davide Mineo, Gennaro Selvaggi, Norma S. Kenyon, Camillo Ricordi, Rodolfo Alejandro

Research output: Contribution to journalArticle

37 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)1695-1701
Number of pages7
JournalTransplantation
Volume86
Issue number12
DOIs
StatePublished - Dec 27 2008

Keywords

  • Alemtuzumab
  • Calcineurin free
  • Graft survival and function
  • Islet transplantation

ASJC Scopus subject areas

  • Transplantation

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