Experience with a Novel Efalizumab‐Based Immunosuppressive Regimen to Facilitate Single Donor Islet Cell Transplantation

• Published in: American journal of transplantation Vol. 10; no. 9; pp. 2082 - 2091
• Main Authors: Turgeon, N. A., Avila, J. G., Cano, J. A., Hutchinson, J. J., Badell, I. R., Page, A. J., Adams, A. B., Sears, M. H., Bowen, P. H., Kirk, A. D., Pearson, T. C., Larsen, C. P.
• Format: Journal Article
• Language: English
• Published: Malden, USA Blackwell Publishing Inc 01-09-2010; Wiley
• Subjects: Adult; Antibodies, Monoclonal - adverse effects; Antibodies, Monoclonal - therapeutic use; Antibodies, Monoclonal, Humanized; Biological and medical sciences; CD11 antigen; Daclizumab; Diabetes mellitus; Diabetes Mellitus, Type 1 - drug therapy; Diabetes Mellitus, Type 1 - metabolism; Diabetes Mellitus, Type 1 - surgery; Diabetes. Impaired glucose tolerance; Donors; Endocrine pancreas. Apud cells (diseases); Endocrinopathies; Etiopathogenesis. Screening. Investigations. Target tissue resistance; Feasibility Studies; Graft Rejection - prevention & control; Humans; Immunoglobulin G - adverse effects; Immunoglobulin G - therapeutic use; Immunosuppressive agents; Immunosuppressive Agents - adverse effects; Immunosuppressive Agents - therapeutic use; immunosuppressive therapy; Insulin; Insulin - metabolism; Islet cells; islet transplantation; Islets of Langerhans; Islets of Langerhans Transplantation - adverse effects; Male; Medical sciences; Middle Aged; Monoclonal antibodies; Pancreatic islet transplantation; Pilot Projects; Surgery (general aspects). Transplantations, organ and tissue grafts. Graft diseases; Tissue Donors; Transplantation; Treatment Outcome; Endocrinopathy; Suboptimal donor; Human; Drug combination; Diabetes mellitus; Antipsoriatic agent; Langerhans islet; Homograft; Monoclonal antibody; Efalizumab; Recommendation; Immunomodulator; immunosuppressive therapy; Experience; Graft; Application method; islet transplantation; Immunosuppressive agent; Therapeutic protocol; Endocrine pancreas
• ISSN: 1600-6135; 1600-6143
• DOI: 10.1111/j.1600-6143.2010.03212.x

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.
Carefully selected patients with T1DM can be rendered insulin independent after a single islet infusion with a novel efalizumab‐based immunosuppressive regimen.