Aim: We postulated that profound T-cell depletion prior to allotrans- plantation followed by minimization of immunosuppression would facilitate the development of donor specific non-responsiveness (i.e. tolerance) and would therefore lead to a reduced requirement for maintenance immunosuppression. Methods: Between 6/02 and 6/03, 39 unselected cadaveric lung transplant (txp) recipients were treated under a protocol consisting of: 1) recipient T-cell depletion (4–7 mg/kg Thymoglobulin iv (n 37) or 30 mg Campath-1H iv (n 2)) prior to allograft reperfusion and 2) minimal posttxp immunosuppression (tacrolimus (tac) trough target of 10–15 ng/ml and prednisone 5 mg/day). Patients (pts) under- went protocol biopsies, assessment of pulmonary function, peripheral flow cytometry and assessment of alloantibody. Weaning of immunosup- pression was considered 4 – 6 months posttxp and was accomplished by consolidating tac to a daily dose and then spacing doses. Results: Lymphocyte depletion was profound. CD8 cells recovered by 4 months posttxp while CD4 cells remained subnormal for 6 months. 1-year actuarial survival was 87%. The 3 deaths (8%) were from ischemia reperfusion injury, sepsis and diffuse alveolar damage related to rejection. One pt underwent early retxp (7 wks) for graft dysfunction. Seventeen pts (44%) did not require augmentation of immunosuppression from baseline while 11 pts (28%) required 1–2 short courses of steroids and 10 (26%) required further anti-T-cell antibody therapy before returning to baseline therapy. Of 25 pts more than 6 months from txp, weaning has been attempted in 12 and achieved in 10 (83%) (8 are receiving tac 4 times/wk and 2 pts 3 times/wk with good allograft function). Eight pts are receiving a daily tac dose. There has been 1 case each of CMV pneumonitis and PTLD. Opportunistic infections developed in 4 pts and were successfully treated. Conclusion: Our results demonstrate that this approach achieves good outcomes with less maintenance immunosuppression and is consistent with development of variable donor specific hyporespon- siveness.
Results of a tolerance-enhancing protocol in human lung transplantation
Bertani A;
2004-01-01
Abstract
Aim: We postulated that profound T-cell depletion prior to allotrans- plantation followed by minimization of immunosuppression would facilitate the development of donor specific non-responsiveness (i.e. tolerance) and would therefore lead to a reduced requirement for maintenance immunosuppression. Methods: Between 6/02 and 6/03, 39 unselected cadaveric lung transplant (txp) recipients were treated under a protocol consisting of: 1) recipient T-cell depletion (4–7 mg/kg Thymoglobulin iv (n 37) or 30 mg Campath-1H iv (n 2)) prior to allograft reperfusion and 2) minimal posttxp immunosuppression (tacrolimus (tac) trough target of 10–15 ng/ml and prednisone 5 mg/day). Patients (pts) under- went protocol biopsies, assessment of pulmonary function, peripheral flow cytometry and assessment of alloantibody. Weaning of immunosup- pression was considered 4 – 6 months posttxp and was accomplished by consolidating tac to a daily dose and then spacing doses. Results: Lymphocyte depletion was profound. CD8 cells recovered by 4 months posttxp while CD4 cells remained subnormal for 6 months. 1-year actuarial survival was 87%. The 3 deaths (8%) were from ischemia reperfusion injury, sepsis and diffuse alveolar damage related to rejection. One pt underwent early retxp (7 wks) for graft dysfunction. Seventeen pts (44%) did not require augmentation of immunosuppression from baseline while 11 pts (28%) required 1–2 short courses of steroids and 10 (26%) required further anti-T-cell antibody therapy before returning to baseline therapy. Of 25 pts more than 6 months from txp, weaning has been attempted in 12 and achieved in 10 (83%) (8 are receiving tac 4 times/wk and 2 pts 3 times/wk with good allograft function). Eight pts are receiving a daily tac dose. There has been 1 case each of CMV pneumonitis and PTLD. Opportunistic infections developed in 4 pts and were successfully treated. Conclusion: Our results demonstrate that this approach achieves good outcomes with less maintenance immunosuppression and is consistent with development of variable donor specific hyporespon- siveness.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
