title: Multicenter Australian trial of islet transplantation: improving accessibility and outcomes.
abstract: Whilst initial rates of insulin independence following islet transplantation are encouraging, long-term function using the Edmonton Protocol remains a concern. The aim of this single-arm, multicenter study was to evaluate an immunosuppressive protocol of initial antithymocyte globulin (ATG), tacrolimus and mycophenolate mofetil (MMF) followed by switching to sirolimus and MMF. Islets were cultured for 24 h prior to transplantation. The primary end-point was an HbA1c of <7% and cessation of severe hypoglycemia. Seventeen recipients were followed for ≥ 12 months. Nine islet preparations were transported interstate for transplantation. Similar outcomes were achieved at all three centers. Fourteen of the 17 (82%) recipients achieved the primary end-point. Nine (53%) recipients achieved insulin independence for a median of 26 months (range 7-39 months) and 6 (35%) remain insulin independent. All recipients were C-peptide positive for at least 3 months. All subjects with unstimulated C-peptide >0.2 nmol/L had cessation of severe hypoglycemia. Nine of the 17 recipients tolerated switching from tacrolimus to sirolimus with similar graft outcomes. There was a small but significant reduction in renal function in the first 12 months. The combination of islet culture, ATG, tacrolimus and MMF is a viable alternative for islet transplantation.
authors.affiliation: National Pancreas Transplant Unit, University of Sydney at Westmead Hospital, Australia. philip.oconnell@wsahs.nsw.gov.au
authors.forename: P J
authors.initials: PJ
authors.lastname: O'Connell
authors.forename: D J
authors.initials: DJ
authors.lastname: Holmes-Walker
authors.forename: D
authors.initials: D
authors.lastname: Goodman
authors.forename: W J
authors.initials: WJ
authors.lastname: Hawthorne
authors.forename: T
authors.initials: T
authors.lastname: Loudovaris
authors.forename: J E
authors.initials: JE
authors.lastname: Gunton
authors.forename: H E
authors.initials: HE
authors.lastname: Thomas
authors.forename: S T
authors.initials: ST
authors.lastname: Grey
authors.forename: C J
authors.initials: CJ
authors.lastname: Drogemuller
authors.forename: G M
authors.initials: GM
authors.lastname: Ward
authors.forename: D J
authors.initials: DJ
authors.lastname: Torpy
authors.forename: P T
authors.initials: PT
authors.lastname: Coates
authors.forename: T W
authors.initials: TW
authors.lastname: Kay
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D001315:Australia / Q000453:epidemiology; D001786:Blood Glucose / Q000378:metabolism; D002478:Cells, Cultured; D003922:Diabetes Mellitus, Type 1 / Q000097:blood / Q000601:surgery*; D005260:Female; D005500:Follow-Up Studies; D006084:Graft Rejection / Q000453:epidemiology / Q000517:prevention & control*; D006085:Graft Survival; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use*; D015994:Incidence; D007328:Insulin / Q000097:blood; D016381:Islets of Langerhans Transplantation / Q000379:methods*; D008297:Male; D008875:Middle Aged; D012189:Retrospective Studies; D020123:Sirolimus / Q000627:therapeutic use; D016559:Tacrolimus / Q000627:therapeutic use; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D001786:Blood Glucose; D007166:Immunosuppressive Agents; D007328:Insulin; D020123:Sirolimus; D016559:Tacrolimus