Long‐Term Laryngeal Allograft Survival Using Low‐Dose Everolimus

Abstract

Everolimus successfully prevents laryngeal allograft rejection up to 60 days posttransplantation. It appears to increase the production of regulatory T-cells while decreasing cytotoxic T-cell and dendritic cell response. Everolimus alone or in combination with other immunosuppressants may enable laryngeal transplantation to become a viable reconstructive option following laryngectomy for malignancy.

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

“…15 Furthermore, the antitumor properties of everolimus are especially promising for patients who have undergone laryngectomy for cancer. 3 It is notable that in the current study, daily everolimus therapy beginning 180 days after the operation could effectively preserve allografts for an additional 90 days. Although the study showed that daily monotherapy with everolimus did not prevent allograft rejection indefinitely, it suggests that the immunosuppressive effects of everolimus are enhanced after combined pulsing with anti-αβ TCR.…”

“…Promising data from our laboratory show that everolimus as a single agent effectively affords long-term allograft survival in mice. 3 Low-dose monotherapy is better tolerated and avoids the side effects commonly observed with additional agents. 15 Furthermore, the antitumor properties of everolimus are especially promising for patients who have undergone laryngectomy for cancer.…”

“…However, it is associated with many sequelae, including loss of vocal function, difficulty with maintenance of the stoma, loss of taste and smell, and social isolation. [1][2][3] Transplantation of the larynx can obviate the aforementioned sequelae by facilitating the return of human voice and the potential for normal respiration. 2 Potter and Birchall 4 found that 75% of laryngectomy patients would accept a transplant if offered.…”

The current status of human laryngeal transplantation in 2017: A state of the field review

“…Because of the well‐documented risk of cancer recurrence following laryngeal transplantation, everolimus has been studied extensively in murine laryngeal transplant models to evaluate its immunosuppressive and antineoplastic activity. Lott et al showed that everolimus monotherapy successfully prevented laryngeal allograft rejection in mice at 60 days post‐transplantation, and appeared to increase the production of regulatory T cells while decreasing the cytotoxic T‐cell dendritic response, creating a favorable environment for transplantation . Everolimus was then used as a combination therapy in a pulsed‐dose regimen to reduce the total amount of immunosuppression and induce tolerance .…”

“…Lott et al showed that everolimus monotherapy successfully prevented laryngeal allograft rejection in mice at 60 days post-transplantation, and appeared to increase the production of regulatory T cells while decreasing the cytotoxic T-cell dendritic response, creating a favorable environment for transplantation. 36 Everolimus was then used as a combination therapy in a pulsed-dose regimen to reduce the total amount of immunosuppression and induce tolerance. 37 Khariwala et al 38 evaluated the effects of irradiation, cyclosporine, combination therapy, pulsed immunosuppression and everolimus on antitumoral activity, showing in a mouse study of squamous cell carcinoma that the use of everolimus resulted in an approximately 50% decrease in local tumor growth, as well as a reduction in distant spread.…”