Minimization and withdrawal of steroids in pancreas and islet transplantation

Davide Mineo, Junichiro Sageshima, George W. Burke, Camillo Ricordi

Research output: Contribution to journalReview article

28 Scopus citations

Abstract

For reducing the corticosteroid (CS)-related side-effects, especially cardiovascular events, CS-sparing protocols have become increasingly common in pancreas transplantation (PT). Lympho-depleting induction antibodies, such as rabbit anti-thymocyte globulin (rATG) or alemtuzumab, have been widely used in successful trials. The results of various CS-sparing protocols combining calcineurin inhibitors (CNI) and mycophenolate or sirolimus, have been mixed for rejection and survival rates. Most of the studies were uncontrolled trials of low-risk patients, therefore the grade of evidence is limited. Large-scale prospective studies with long-term follow up are necessary to assess risks and benefits of CS-sparing regimens in PT before recommending such strategies as standard practice. Islet allo-transplantation for patients with brittle type 1 diabetes mellitus, less invasive and safer procedure than PT, has been attempted since late 1980s, but diabetogenic immunosuppressants at maintenance, mainly CS and high-dose CNI, prevented satisfactory results (10% insulin-independence at 1-year post-transplant). Since 2000, CS-free and CNI-reducing protocols, including more potent induction [daclizumab, OKT3γ1(ala-ala) anti-CD3 antibody, rATG] and maintenance (sirolimus, mycophenolate) agents, have significantly improved short-term outcomes whereas long-term are still inadequate (from 80% to 20% insulin-independence from 1- to 5-year post-transplant). Main limitations are allo- and autoimmunity, immunosuppression-related islet and systemic toxicity and transplant site unsuitability, which tolerogenic protocols and biotechnological solutions may solve.

Original languageEnglish (US)
Pages (from-to)20-37
Number of pages18
JournalTransplant International
Volume22
Issue number1
DOIs
StatePublished - Jan 1 2009
Externally publishedYes

Keywords

  • Gluco-corticosteroids
  • Immunosuppression
  • Islet transplantation
  • Pancreas transplantation
  • Side-effects
  • Toxicity

ASJC Scopus subject areas

  • Transplantation

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