The IPTA Nashville consensus conference on post-transplant lymphoproliferative disorders after solid organ transplantation in children: IV-consensus guidelines for the management of post-transplant lymphoproliferative disorders in children and adolescents.

The International Pediatric Transplant Association convened an expert consensus conference to assess current evidence and develop recommendations for various aspects of care relating to post-transplant lymphoproliferative disorders (PTLD) after pediatric solid organ transplantation. This report addresses the outcomes of deliberations by the PTLD Management Working Group. A strong recommendation was made for reduction in immunosuppression as the first step in management. Similarly, strong recommendations were made for the use of the anti-CD20 monoclonal antibody (rituximab) as was the case for chemotherapy in selected scenarios. In some scenarios, there is uncoupling of the strength of the recommendations from the available evidence in situations where such evidence is lacking but collective clinical experiences drive decision-making. Of note, there are no large, randomized phase III trials of any treatment for PTLD in the pediatric age group. Current gaps and future research priorities are highlighted.

Similarities and Differences in Allocation Policies for Pediatric Liver Transplantation Across the World.

OBJECTIVES: We aimed to investigate national allocation policies for pediatric liver transplantation (LT). METHOD: A survey was prepared by the European Society for Paediatric Gastroenterology Hepatology and Nutrition Hepatology Committee in collaboration with the North American Studies of Pediatric Liver Transplantation consortium. The survey was sent to pediatric hepatologists and transplant surgeons worldwide. National data were obtained from centrally based registries. RESULTS: Replies were obtained from 15 countries from 5 of the world continents. Overall donation rate varied between 9 and 35 per million inhabitants. The number of pediatric LTs was 4 to 9 per million inhabitants younger than 18 years for 13 of the 15 respondents. In children younger than 2 years mortality on the waiting list (WL) varied between 0 and 20%. In the same age group, there were large differences in the ratio of living donor LT to deceased donor LT and in the ratio of split liver segments to whole liver. These differences were associated with possible discrepancies in WL mortality. CONCLUSIONS: Similarities but also differences between countries were detected. The described data may be of importance when trying to reduce WL mortality in the youngest children.

The Health Care Transition of Youth With Liver Disease Into the Adult Health System: Position Paper From ESPGHAN and EASL.

BACKGROUND: Medical advances have dramatically improved the long-term prognosis of children and adolescents with once-fatal hepatobiliary diseases. However, there is no generally accepted optimal pathway of care for the transition from paediatric care to the adult health system. AIM: The purpose of this position paper is to propose a transition process for young people with paediatric onset hepatobiliary diseases from child-centred to adult-centred healthcare services. METHODS: Seventeen ESPGHAN/EASL physicians from 13 countries (Austria, Belgium, France, Germany, Hungary, Italy, the Netherlands, Norway, Poland, Spain, Sweden, Switzerland, and United Kingdom) formulated and answered questions after examining the currently published literature on transition from childhood to adulthood. PubMed and Google Scholar were systematically searched between 1980 and January 2018. Quality of evidence was assessed by the Grading of Recommendation Assessment, Development and Evaluation (GRADE) system. Expert opinions were used to support recommendations whenever the evidence was graded weak. All authors voted on each recommendation, using the nominal voting technique. RESULTS: We reviewed the literature regarding the optimal timing for the initiation of the transition process and the transfer of the patient to adult services, principal documents, transition multi-professional team components, main barriers, and goals of the general transition process. A transition plan based on available evidence was agreed focusing on the individual young people's readiness and on coordinated teamwork, with transition monitoring continuing until the first year of adult services.We further agreed on selected features of transitioning processes inherent to the most frequent paediatric-onset hepatobiliary diseases. The discussion highlights specific clinical issues that will probably present to adult gastrointestinal specialists and that should be considered, according to published evidence, in the long-term tracking of patients. CONCLUSIONS: Transfer of medical care of individuals with paediatric onset hepatobiliary chronic diseases to adult facilities is a complex task requiring multiple involvements of patients and both paediatric and adult care providers.

Prevention and treatment for Epstein-Barr virus infection and related cancers.

Epstein-Barr virus (EBV) was the first herpes virus described as being oncogenic in humans. EBV infection is implicated in post-transplant lymphoproliferative diseases (PTLD) and several other cancers in non-immunocompromised patients, with more than 200,000 new cases per year. While prevention of PTLD is improving, mainly based on EBV monitoring and preemptive tapering of immunosuppression, early diagnosis remains the best current option for the other malignancies. Significant progress has been achieved in treatment, with decreased mortality and morbidity, but some challenges are still to face, especially for the more aggressive diseases. Possible prevention by EBV vaccination would be a more global approach of this public health problem, but further active research is needed before this goal could be reached.

Prope tolerance after pediatric liver transplantation.

pT, under mono- and infratherapeutic calcineurin inhibition, may constitute an optimal condition combining graft acceptance with low IS load and minimal IS-related toxicity. We reviewed 171 pediatric (<15.0 yr) survivors beyond one yr after LT, transplanted between April 1999 and June 2007 under tacrolimus-based regimens (median follow-up post-LT: 6.0 yr, range: 0.8-9.5 yr). Their current status regarding IS therapy was analyzed and correlated with initial immunoprophylaxis. pT was defined as tacrolimus monotherapy, with mean trough blood levels <4 ng/mL during the preceding year of follow-up, combined with normal liver function tests. The 66 children transplanted before April 2001 received a standard tacrolimus-steroid regimen. Beyond April 2001, 105 patients received steroid-free tacrolimus-basiliximab or tacrolimus-daclizumab immunoprophylaxis. In the latter group, 43 (41%) never experienced any acute rejection episode and never received steroids. In the long term, a total of 79 recipients (47%) developed pT (n = 73) or IS-free operational tolerance (n = 6), 27 of them belonging to the 43 steroid-free patients (63%). In contrast, only 52/128 (41%) children treated with steroids subsequently developed prope/operational tolerance (p = 0.012). Steroid-free tacrolimus-based IS seems to promote long-term graft acceptance under minimal/no IS. These results constitute the first evidence that minimization of IS, including steroid avoidance, might be tolerogenic in the long term after pediatric LT.

Steroid-free, tacrolimus-basiliximab immunosuppression in pediatric liver transplantation: clinical and pharmacoeconomic study in 50 children.

Corticosteroid-free immunosuppression (IS) may be potentially beneficial for transplanted patients, particularly children. The purpose of this study was to evaluate the efficacy and cost of such strategy in primary pediatric liver transplantation (LT). Fifty pediatric LT recipients were prospectively treated with a steroid-free, tacrolimus-basiliximab-based IS (group TB). A group of 34 children transplanted under a conventional tacrolimus-steroids regimen served as control series (group TS). Groups TB and TS were compared regarding patient and graft survival, rejection incidence, infectious complications, and growth, as well as cost of the transplant procedure. Patient and graft survivals at 3 years were 96% and 94% in group TB, versus 91% and 88% in group TS (P = 0.380 and P = 0.370, respectively). Rejection-free graft survival at 3 years was 72% in group TB, versus 41% in group TS (P = 0.007). Patients in group TB had significantly less viral infections than patients in group TS (P = 0.045). Height standard deviation score was significantly enhanced in children from group TB, when compared to group TS. Medical care costs were similar in both groups. Steroid avoidance together with basiliximab immunoprophylaxis was not harmful in terms of allograft acceptance, and even seemed to be beneficial in the long term.