Ten-Month Laryngeal Allograft Survival with Use of Pulsed Everolimus and Anti—αβ T-Cell Receptor Antibody Immunosuppression

Abstract

Objectives: The risks of daily immunosuppression limit the use of laryngeal transplantation as a reconstructive option. Pulsed immunosuppressive dosing can lessen these risks. The study objective was to develop a long-term pulsing regimen that minimizes exposure to immunosuppressive agents. Methods: Rat laryngeal transplantation was performed. Everolimus (1 mg/kg per day) and anti–αβ T-cell receptor (TCR) antibodies (250 μg) were given for 7 days beginning 1 day before transplantation and for 5 days beginning on day 90 after transplantation. On day 180, group 1 (n = 5) received the initial regimen for 3 days, and group 2 (n = 5) received everolimus (1 mg/kg per day) until euthanization, which occurred when parathyroid hormone (PTH) levels dropped to less than 11 pg/mL or at 300 days. Results: Four of the 5 rats in group 1 had normal PTH levels at 300 days. The PTH level for 1 rat was less than 11 pg/mL at 270 days. In group 2, none of the 5 rats had normal PTH levels at 300 days. Two had PTH levels below 11 pg/mL at 270 days, and 3 had PTH levels below 11 pg/mL at 300 days. The allografts that survived beyond 300 days had an essentially normal histologic appearance. Conclusions: Pulsed immunosuppression prevented allograft rejection for 10 months and was more effective than daily everolimus. Short-term perioperative therapy followed by pulsed, tapered dosing is a viable alternative to traditional regimens and may decrease associated risks.