Immunological Aspects and Immunomodulation

Abstract

Vascularised composite tissue allotransplantation (VCA) is a new transplant discipline of reconstructive plastic surgery that relies on the restoration of deformity and/or amputation by the allotransplantation of different tissues and organs from another person (the donor). As in any other solid organ transplant discipline, graft survival depends on the acceptance of transplanted tissues and organs on the recipient and the absence or control of rejection episodes. In 1997, the Louisville team proved that long-term survival of transplanted limbs could be achieved in an experimental model with a triple-drug therapy (steroid, tacrolimus and mycophenolate mofetil). Soon afterwards, the first human hand transplants were a reality in 1998. The first experiences received the same immunosuppression regime, with excellent long-term results (both functional and immunological) to date. The current success of VCA is a promising field in plastic and reconstructive surgery. Intense research is currently being undertaken to improve the immune tolerance of composite tissues, since long-term results and face or limb acceptance depend on immune regulation and the control of side effects.

Appendix 11.1: HUVH Immunosuppression Protocol

11.1.1 Induction Therapy

• 1. Preoperative infusion of Thymoglobulin (atg) as soon as the patient arrives at the hospital, at a dose of 2 mg/kg. Premedicate with 1 g of methylprednisolone IV, Benadryl 50 mg IV and acetaminophen 650 mg PO.

• 2. Revascularisation: Administer 1 g of methylprednisolone IV, 30 min before revascularisation.

• 3. Thymoglobulin (atg), 2 mg/kg/day for 5 days (start preoperatively).

• 4. Methylprednisolone:

  • Days 1–14: Administer a dose of 2 mg/kg/day.

  • Taper down the dose of methylprednisolone over time to 10 mg/day.

• 5. Tacrolimus 0.15 mg/kg/day divided into two doses. Start treatment preoperatively.

• 6. Mycophenolate mofetil: Initial dose of 1 g two times a day (total dose of 2 g). Start preoperatively. Adjust according to leucocyte count and stop 1 year after the transplant.

11.1.2 Maintenance Therapy

• 1. Tacrolimus: Serum target levels of 10–15 ng/ml during the first 6 months (months 1–6 posttransplant) and target levels of 5–10 ng/ml after 6 months posttransplant.

• 2. Mycophenolate mofetil: Adjust levels according to leucocyte count.

• 3. Methylprednisolone: Taper down levels to 10 mg/day. Consider lower levels or alternate levels if good response.

• 4. Topical tacrolimus 0.1 % 2 times/day for 2 months (start on day 10 posttransplant).

11.1.3 Treatment of Acute Rejection

• 1. Increase the dose of tacrolimus if serum blood level is <15 ng/ml.

• 2. Methylprednisolone, 1 g/day/IV for 3 days.

• 3. If severe rejection: Methylprednisolone 5 mg/kg IV in 4 doses with quick taper over 5 days.

• 4. Consider topical tacrolimus and steroids.

• 5. Steroid-resistant rejection:

  • (a) OKT3 5 mg/day/IV for 7 days

  • (b) Thymoglobulin (atg) 2 mg/kg/day for 3 days

• 6. In repeated severe acute rejections, consider extracorporeal photopheresis.