Minimal but essential doses of immunosuppression: a more realistic approach to improve long-term outcomes for pediatric living-donor liver transplantation.

University of Cambridge
Transplantation (Impact Factor: 3.78). 04/2011; 91(7):808-10. DOI: 10.1097/TP.0b013e31820f07de
Source: PubMed
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Transplanting a uterus has unique characteristics, since a successful outcome is represented only by the birth of a viable healthy child. For this reason, critical issues in this type of transplantation differ profoundly from those of other solid organs and, beside a functioning uterus, involve 3 additional steps. First, at the time of implantation, the quality of embryo is tested by specialized decidual cells surrounding the implanting embryo; such testing is aimed at allowing the development of a normal embryo. Second, from early gestation onward, blood supply to the uterus increases from 45 to 750mL per minute. Vascular anastomoses should support such a marked increase in blood flow. Third, full transformation of spiral arterioles in the placental bed is required to direct 75% of the uterine blood flow to the intervillous space. Unfortunately, no suitable animal model is available for experimentation. Three overarching ethical issues must be considered. Should organ transplant be conducted when it is not absolutely necessary as a life-saving or quality-of-life-saving measure? To what extent should medicine delimit its potential in spite of societal desires? Should society demand from medicine the application of whichever technology can be developed and, if so, to what extent?
    International journal of gynaecology and obstetrics: the official organ of the International Federation of Gynaecology and Obstetrics 07/2013; 123(2). DOI:10.1016/j.ijgo.2013.05.010 · 1.56 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: To outline the rationale of powerful depleting induction therapy with alemtuzumab and minimal maintenance immunosuppression after organ transplantation. The original observations in principle have been confirmed by many independent centres. Follow-up of the 'prope tolerance' protocol has confirmed a low incidence of rejection, infection and post transplant lymphoproliferative disorder (PTLD). Especially, encouraging results were obtained in African-Americans. There were few side effects and the regimen was well tolerated by patients. Treg cells were observed in the circulation, which could be an important factor in the mechanisms of graft acceptance using a prope tolerance regimen. There was a considerable reduction in the costs of the transplantation procedure. It is suggested that this minimalisation of maintenance immunosuppression is the best therapy currently available that we can offer to our patients.
    Current opinion in organ transplantation 06/2011; 16(4):353-8. DOI:10.1097/MOT.0b013e328348b44c · 2.38 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Pediatric recipients of living-donor liver transplants (LDLT) can often discontinue immunosuppression (IS). We examined factors affecting development of operational tolerance (OT), defined as off IS for >1 year, in this population. A historic cohort analysis was conducted in 134 pediatric primary semi-allogeneic LDLT. Multivariate logistic regression analysis was used. The frequency of peripheral regulatory T cells (Tregs) was determined at >10 years post-Tx by FACS analysis. IS was successfully discontinued in 84 tolerant patients (Gr-tol), but not in 50 intolerant patients (Gr-intol). The Gr-intol consisted of 24 patients with rejection (Gr-rej) and 26 with fibrosis of grafts (Gr-fib). The absence of early rejection [odds ratio (OR) 2.79, 95% CI 1.11-7.02, P = 0.03], was a positive independent predictor, whereas HLA-A mismatch (0.18, 0.03-0.91, P = 0.04) was a negative predictor. HLA-DR mismatches did not affect OT. The Treg frequency was significantly decreased in Gr-intol (4.9%) compared with Gr-tol (7.6%) (P = 0.003). There were increased levels of tacrolimus in the first week in Gr-Tol (P = 0.02). Although HLA-B mismatch (8.73, 1.09-70.0, P = 0.04) was a positive independent predictor of OT, its clinical significance remains doubtful. In this large cohort of pediatric LDLT recipients, absence of early rejection, HLA-A match and the later predominance of Tregs are factors associated with OT.
    Transplant International 11/2011; 25(1):97-106. DOI:10.1111/j.1432-2277.2011.01389.x · 3.16 Impact Factor