title: Experience with a novel efalizumab-based immunosuppressive regimen to facilitate single donor islet cell transplantation.
abstract: Islet transplantation is an experimental therapy for selected patients with type 1 diabetes (T1DM). It remains limited by immunosuppressive drug toxicity, progressive loss of insulin independence, allosensitization and the need for multiple islet donors. We describe our experience with an efalizumab-based immunosuppressive regimen as compared to the prevailing standard regimen, the Edmonton protocol. Twelve patients with T1DM received islet transplants: eight were treated with the Edmonton protocol; four were treated with daclizumab induction, a 6-month course of tacrolimus, and maintenance with efalizumab and mycophenolate mofetil. The primary endpoint was insulin independence after one islet infusion. Only two Edmonton protocol treated patients achieved the primary endpoint; six required islets from multiple donors, and all experienced leukopenia, mouth ulcers, anemia, diarrhea and hypertransaminasemia. Four became allosensitized. All patients treated with the efalizumab-based regimen achieved insulin independence with normal hemoglobin A1c after a single islet cell infusion and remained insulin independent while on efalizumab. These patients experienced significantly fewer side effects and none became allosensitized. Trial continuation was terminated by withdrawal of efalizumab from the market. These data suggest that this efalizumab-based regimen prevents islet rejection, is well tolerated, and allows for single donor islet transplantation.
authors.affiliation: Emory Transplant Center, Department of Surgery, Emory University, Atlanta, GA, USA. nturgeo@emory.edu
authors.forename: N A
authors.initials: NA
authors.lastname: Turgeon
authors.forename: J G
authors.initials: JG
authors.lastname: Avila
authors.forename: J A
authors.initials: JA
authors.lastname: Cano
authors.forename: J J
authors.initials: JJ
authors.lastname: Hutchinson
authors.forename: I R
authors.initials: IR
authors.lastname: Badell
authors.forename: A J
authors.initials: AJ
authors.lastname: Page
authors.forename: A B
authors.initials: AB
authors.lastname: Adams
authors.forename: M H
authors.initials: MH
authors.lastname: Sears
authors.forename: P H
authors.initials: PH
authors.lastname: Bowen
authors.forename: A D
authors.initials: AD
authors.lastname: Kirk
authors.forename: T C
authors.initials: TC
authors.lastname: Pearson
authors.forename: C P
authors.initials: CP
authors.lastname: Larsen
mesh_terms: D000328:Adult; D000911:Antibodies, Monoclonal / Q000009:adverse effects / Q000627:therapeutic use*; D061067:Antibodies, Monoclonal, Humanized; D000077561:Daclizumab; D003922:Diabetes Mellitus, Type 1 / Q000188:drug therapy* / Q000378:metabolism / Q000601:surgery*; D005240:Feasibility Studies; D006084:Graft Rejection / Q000517:prevention & control*; D006801:Humans; D007074:Immunoglobulin G / Q000009:adverse effects / Q000627:therapeutic use; D007166:Immunosuppressive Agents / Q000009:adverse effects / Q000627:therapeutic use*; D007328:Insulin / Q000378:metabolism; D016381:Islets of Langerhans Transplantation / Q000009:adverse effects*; D008297:Male; D008875:Middle Aged; D010865:Pilot Projects; D014019:Tissue Donors; D016896:Treatment Outcome
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D007074:Immunoglobulin G; D007166:Immunosuppressive Agents; D007328:Insulin; D000077561:Daclizumab; C472181:efalizumab