Minimization and withdrawal of steroids in pancreas and islet transplantation.
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, OKT3gamma1(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.
Mineo
Davide
D
Diabetes Research Institute, University of Miami, FL 33136, USA.
Sageshima
Junichiro
J
Burke
George W
GW
Ricordi
Camillo
C
D000305:Adrenal Cortex Hormones / Q000008:administration & dosage* / Q000009:adverse effects; D002318:Cardiovascular Diseases / Q000139:chemically induced / Q000517:prevention & control; D002986:Clinical Trials as Topic; D003922:Diabetes Mellitus, Type 1 / Q000628:therapy; D006085:Graft Survival; D006801:Humans; D007165:Immunosuppression Therapy / Q000379:methods; D007166:Immunosuppressive Agents / Q000009:adverse effects*; D016381:Islets of Langerhans Transplantation / Q000379:methods*; D016035:Pancreas Transplantation / Q000379:methods*; D013375:Substance Withdrawal Syndrome
D000305:Adrenal Cortex Hormones; D007166:Immunosuppressive Agents