Pediatric Transplantation最新文献

Background: Pediatric liver transplantations generally represent advanced surgery for selected patients. In case of acute or chronic graft failure, biliary or vessel complications, a retransplantation (reLT) can be necessary. In these situations massive adhesions, critical patient condition or lack of good vessels for anastomosis often are problematic.

Methods: Between 2008 and 2021, 208 pediatric patients received a liver transplantation at our center. Retrospectively, all cases with at least one retransplantation were identified and stored in a database. Indication, intra- and postoperative course and overall survival (OS) were analyzed.

Results: Altogether 31 patients (14.9%) received a reLT. In 22 cases only one reLT was done, 8 patients received 2 reLTs and 1 patient needed a fourth graft. Median age for primary transplantation, first, second and third reLT was 14 (range: 1-192 months), 60.5 (range: 1-215 months), 58.5 (range: 14-131 months) and 67 months, respectively. Although biliary atresia (42%) and acute liver failure (23%) represented the main indications for the primary liver transplantation, acute and chronic graft failure (1st reLT: 36%, 2nd reLT: 38%), hepatic artery thrombosis (1st reLT: 29%, 2nd reLT: 25%, 3rd reLT: 100%) and biliary complications (1st reLT: 26%, 2nd reLT: 37%) were the most frequent indications for reLT. OS was 81.8% for patients with 1 reLT, 87.5% with 2 reLTs and 100% with 3 reLTs.

Conclusion: Pediatric liver retransplantation is possible with a good outcome even after multiple retransplantations in specialized centers. Nevertheless, careful patient and graft selection, as well as good preoperative conditioning, are essential.

Background: Portal vein thrombosis is a potentially devastating complication following pediatric liver transplantation. In rare instances of complete portomesenteric thrombosis, cavoportal hemitransposition may provide graft inflow. Here we describe long-term results following a case of pediatric cavoportal hemitransposition during liver transplantation and review the current pediatric literature.

Methods: A 9-month-old female with a history of biliary atresia and failed Kasai portoenterostomy underwent living donor liver transplantation, which was complicated by portomesenteric venous thrombosis. The patient underwent retransplantation with cavoportal hemitransposition on postoperative day 12.

Outcome: The patient recovered without further complication, and 10 years later, she continues to do well, with normal graft function and no clinical sequelae of portal hypertension. CT scan with 3-D vascular reconstruction demonstrated recanalization of the splanchnic system, with systemic drainage to the inferior vena cava via an inferior mesenteric vein shunt. The cavoportal anastomosis remains patent with hepatopetal flow. Of the 12 previously reported cases of pediatric cavoportal hemitransposition as portal inflow in liver transplantation, this is the longest-known follow-up with a viable allograft. Notably, sequelae of portal hypertension were also rare in the 12 previously reported cases, with no cases of long-term renal dysfunction, lower extremity edema, or ascites.

Conclusions: Long-term survival beyond 10 years with normal graft function is feasible following pediatric cavoportal hemitransposition. Complications related to portal hypertension were generally short-lived, likely due to the development of robust collateral circulation. Additional reports of long-term outcomes are necessary to facilitate informed decision making when considering pediatric cavoportal hemitransposition for liver graft inflow.

Epstein-Barr Virus (EBV) is a ubiquitous herpes type virus that is associated with post-transplant lymphoproliferative disorder (PTLD). Usual management includes reduction or cessation of immunosuppression and in some cases chemotherapy including rituximab. However, limited therapies are available if PTLD is refractory to rituximab. Several clinical trials have investigated the use of EBV-directed T cells in rituximab-refractory patients; however, data regarding response is scarce and inconclusive. Herein, we describe a patient with EBV-PTLD refractory to rituximab after orthotopic heart transplantation (OHT) requiring EBV-directed T-cell therapy. This article aims to highlight the unique and aggressive clinical presentation and progression of PTLD with utilization of EBV-directed T-cell therapy for management and associated pitfalls.

Introduction: Tacrolimus is the standard immunosuppressant for pediatric kidney transplants and is routinely administered twice daily (BD-tac). Envarsus (LCP-tac), an extended-release formulation, is approved for adults but not for pediatric patients.

Methods: We conducted a pilot open-label phase 1 study in stable pediatric kidney transplant recipients (age < 18 at the time of study). Our primary objective was to compare the pharmacokinetics (Pk) of LCP-tac versus BD-tac. We conducted two 24-h Pk studies: pre-conversion (BD-tac) and 4 weeks post-conversion to LCP-tac. Patients were followed for 6 months, with the option to continue LCP-tac.

Results: Five patients completed the study, with no returns to BD-tac. Median age was 15 years (range 11-17). LCP-tac exhibited an extended-release profile versus the bimodal profile of BD-tac. Time to maximum concentration was delayed (5 h vs. 1 h), and maximum concentration was lower (9.9 ng/mL vs. 14.4 ng/mL). Tacrolimus area under the curve (24 h) was comparable (141 ± 46.5 ng/mL vs. 164 ± 27.8 ng/mL). No new safety concerns arose. There were no rejection and no difference in eGFR at the study's end (1.5 mL/min/1.73 m² , range - 1.7 to 2.3 mL/min/1.73 m² ). Concentration/dose ratio was higher in LCP-tac (1.8 ± 0.64 vs. 0.8 ± 0.39). The final conversion ratio was 0.6 (BD-tac: LCP-tac).

Conclusion: Our pilot study confirms the extended-release Pk profile and improved absorption of LCP-tac compared to BD-tac. A larger study is needed to further evaluate the population Pk characteristics in children.

Background: Valganciclovir is approved for cytomegalovirus prophylaxis in pediatrics using the Pescovitz algorithm. There are reports of valganciclovir overdoses in children with low body surface area and overestimated creatinine clearance utilizing this algorithm. This study compared the incidence of neutropenia and cytomegalovirus infection between the Pescovitz and weight-based dosing algorithms.

Methods: A single-center retrospective chart review from January 2010 to September 2018 was performed on pediatric heart, liver, and kidney transplant recipients, who received valganciclovir. Data were collected from the initiation of valganciclovir prophylaxis to 30 days after discontinuation. The primary objective was the incidence of neutropenia in patients receiving valganciclovir dosed by the Pescovitz versus weight-based dosing algorithms.

Results: This study included 187 pediatric transplant recipients who received valganciclovir dosed via the Pescovitz (62 recipients) or weight-based dosing algorithms (125 recipients). The incidence of neutropenia was higher in the Pescovitz (69.4%) compared to the weight-based dosing group (53.6%; p = .04) including moderate and severe neutropenia. Cytomegalovirus viremia was not significantly different between the two groups and occurred in 4.8% of the Pescovitz group compared to 2.4% of the weight-based group (p = .4).

Conclusions: The incidence of neutropenia was greater in recipients receiving valganciclovir dosed via the Pescovitz algorithm compared to the weight-based dosing. There were no significant differences in regard to cytomegalovirus viremia or disease between the two groups.

Background: Immunosuppression after heart transplantation (HTX) with mammalian target of rapamycin (mTOR) inhibitors serves as a prophylaxis against rejection and to treat coronary vascular injury. However, there is little data on the early, preventive use of everolimus after pediatric HTX.

Methods: Retrospective study of 61 pediatric HTX patients (48 cardiomyopathy and 13 congenital heart disease), 28 females, median age 10.1 (range 0.1-17.9) years transplanted between 2008 and 2020. We analyzed survival, rejection, renal function, occurrence of lymphoproliferative disorder, and allograft vasculopathy together with adverse effects of early everolimus therapy combined with low-dose calcineurin inhibitors.

Results: Everolimus therapy was started at a median 3.9 (1-14) days after HTX. Median follow-up was 4.3 (range 0.5-11.8) years, cumulative 184 patient years. The estimated 1- and 5-year survival probability was 89% (CI 82%:98%) and 87% (CI 78%:97%). Four patients developed rejection (6.6%) (maximum 2R ISHLT criteria). No patient suffered from chronic renal failure. Three patients (4.9%) developed post-transplant lymphoproliferative disorder. Five patients suffered relevant wound-healing disorders after transplantation, four of them carrying relevant risk factors before HTX (mechanical circulatory support (n = 3), delayed chest closure after HTX (n = 3)). No recipient developed cardiac allograft vasculopathy.

Conclusion: Initiating everolimus within the first 14 days after HTX seems to be well tolerated, enabling a low incidence of rejection, post-transplant lymphoproliferative disorders, renal failure, and reveals no evidence of cardiac allograft vasculopathy as well as good overall survival in pediatric heart transplant recipients.

Background: BK viremia after kidney transplantation (KT) poses significant risk for BK virus-associated nephropathy and impacts graft survival. Conventional treatment involves reduction of immunosuppression, which in turn may increase risk for rejection. To address this dilemma, use of anti-viral therapy with immunosuppressive properties such as leflunomide is an attractive option.

Methods: We performed a multi-center, retrospective chart review to report tolerability and effectiveness of leflunomide use for the eradication of BK viremia and prevention of BK virus-associated nephropathy in pediatric KT recipients.

Results: Seventy patients prescribed leflunomide were included and were followed up from initiation until 1 year following leflunomide completion. BK viremia was eradicated in 64 (91.4%) patients including 8 of 11 with nephropathy (BKVN) on initial biopsy. Reduced anti-proliferative medication (AP) dosing was not associated with increase in biopsy proven rejection (BPAR). However, complete discontinuation of AP during leflunomide therapy was associated with increase in BPAR in uni- and multivariate logistic regression, as was targeted reduction in calcineurin inhibitor (CNI) trough goals. One graft was lost to BKVN. There was no significant association found between time to BK eradication and leflunomide trough concentration, mycophenolate dose reduction, or steroid use (univariate logistic regression). Few leflunomide adverse drug reactions (ADR) were reported (most commonly: gastrointestinal, hematologic).

Conclusion: Leflunomide is a promising adjunctive treatment to immunosuppression reduction for BK virus eradication with minimal ADR. AP reduction, not discontinuation, and judicious reduction in CNI trough goals with close monitoring, is a promising strategy for treatment of BK viremia with concomitant use of leflunomide therapy.