Open AccessMinimization and withdrawal of steroids in pancreas and islet transplantation
Author(s) -
Mineo Davide,
Sageshima Junichiro,
Burke George W.,
Ricordi Camillo
Publication year - 2009
Publication title -
transplant international
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.998
H-Index - 82
eISSN - 1432-2277
pISSN - 0934-0874
DOI - 10.1111/j.1432-2277.2008.00761.x
Subject(s) - medicine , daclizumab , immunosuppression , calcineurin , alemtuzumab , sirolimus , transplantation , rituximab , islet cell transplantation , tacrolimus , type 1 diabetes , islet , diabetes mellitus , insulin , endocrinology , lymphoma
Summary 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.