Pediatric Transplantation最新文献

Background: Hematopoietic cell transplantation (HCT) is the only curative treatment for chronic active Epstein-Barr virus infection (CAEBV). While HCT is needed at the appropriate time, there are sometimes difficulties in securing an appropriate donor, making HLA haploidentical donor an alternative option. Recently, post-transplant cyclophosphamide (PTCy) has rapidly gained popularity as a safe graft-versus-host disease (GVHD) prevention strategy for HCT from HLA haploidentical donors; however, there are only a few reports of its use for CAEBV.

Method: A retrospective chart review was completed for two pediatric CAEBV cases who underwent HLA haploidentical HCT (Haplo-HCT) with PTCy.

Result: A 6-year-old girl diagnosed with CAEBV previously underwent HCT twice from an HLA 8/8 matched brother, which both failed due to secondary graft failure. A third HCT was planned with a peripheral blood stem cell from her haploidentical father. She received a busulfan-based reduced intensity conditioning regimen. PTCy, mycophenolate mofetil, and tacrolimus were used for GVHD prophylaxis. Engraftment was achieved with full donor chimerism, and she remained in complete remission. A 7-year-old girl also diagnosed with CAEBV underwent HCT from her haploidentical mother with the same conditioning regimen and GVHD prophylaxis as the previous case. Engraftment was achieved with full donor chimerism. She suffered grade II (skin stage 3) acute GVHD and transplant-associated thrombotic microangiopathy, which were both treated successfully. She remained in complete remission.

Conclusions: Haplo-HCT with PTCy was safely performed for two pediatric CAEBV patients. Haplo-HCT may be a useful transplant option for CAEBV patients without a matched donor option.

Background: With advances in respiratory care allowing for improved survival, cardiomyopathy has emerged as the leading cause of death in patients with Duchenne Muscular Dystrophy (DMD). As end-stage heart failure emerges as the primary life-limiting complication in DMD patients, their consideration for advanced heart failure therapies, including ventricular assist devices (VADs) and/or heart transplantation (HT), is increasing. To date, however, there are few published reports of HT in DMD patients.

Methods: We report a case of HT in an 18-year-old young man with DMD, end-stage heart failure, respiratory insufficiency requiring nocturnal noninvasive ventilation, and retained ambulation with the use of a cane, who was declined for VAD and HT at an adult heart transplant center; he then received an LVAD, followed by HT after 362 days of support at a pediatric center.

Results: At 3.5 years of follow-up, the patient has excellent graft function and modestly improved pulmonary mechanics, though has experienced a functional decline from ambulatory status to the need for full assistance with activities of daily living.

Conclusions: This case underscores the importance of individual consideration for HT in patients with DMD, provides additional insight into the unique risks of VAD support in these patients, and further builds upon the existing experience that acceptable post-HT outcomes are achievable in this population.

Background: Pediatric heart transplant recipients have high rates of alloantibody development and antibody-mediated rejection (AMR). Daratumumab is a novel therapy that targets plasma cells and has been utilized in transplant populations, but data in pediatric populations are limited. Here, we describe the utilization of daratumumab in pediatric heart transplant recipients.

Methods: Twelve patients at a single institution were treated with daratumumab for AMR (n = 9) or anti-HLA antibody desensitization (n = 3). Three doses of daratumumab were administered with additional doses based on clinical response. For AMR, response to daratumumab was evaluated based on hemodynamics, histopathology, biopsy mRNA expression profiling, ejection fraction, donor-specific antibody titers, and donor-derived cell-free DNA fraction. For desensitization, cPRA pre- and post-daratumumab were reported.

Results: Sixty-five daratumumab infusions were administered to 12 patients (age 0.5-24 years; weight 8-90 kg). Infusion reactions occurred in 12% of infusions; however, none required discontinuation. Nine patients (75%) experienced infection; most were common childhood infections and did not require hospitalization. All 9 AMR patients showed improvement in AMR, and those with chronic AMR benefitted from repeat daratumumab administration. All desensitization patients had dramatic declines in cPRA, and two underwent successful transplantation without rejection 9 months post-transplant.

Conclusions: We report that daratumumab is safe and effective in a small series of pediatric heart transplant patients, including patients as young as 6 months old. Daratumumab could prove to be a valuable tool for desensitization and AMR treatment; however, additional studies are needed to corroborate these findings and determine long-term outcomes.

Background: Pediatric kidney transplant recipients require periodic biopsy for active surveillance to prolong allograft half-life, and non-invasive MR imaging markers are needed but understudied. Here we aimed to determine the feasibility of MR diffusion tensor imaging (DTI) on pediatric kidney transplant recipients, compare transplanted kidneys DTI values to healthy controls, and correlate DTI values with allograft histopathology.

Methods: Single-center prospective study of pediatric (< 18 years of age) kidney transplant recipients undergoing biopsies and healthy controls between February 2020 and October 2023. MRI DTI-derived metrics (fractional anisotropy [FA] and track length) of the kidney cortex were obtained for all participants. Transplant recipients versus controls, rejection versus non-rejection, and high chronic allograft damage index (CADI) versus low were compared using two-sample t-test or Wilcoxon rank-sum test.

Results: Fifteen transplant recipients (4F/11M, median 16 [IQR 13-18] years old) and 15 healthy controls (9F/6M, median 15 [IQR 12-22] years old, 30 kidney units) were evaluated. DTI was technically appropriate in all cases. Smaller FA values and longer track length were found in allografts (FA in allografts (median [IQR]: 0.25 [0.25-0.28]) vs. controls (0.28 [0.27-0.33], p = 0.003) and track length in allografts (mean: 19.36 ± 5.21) vs. controls (12.80 ± 3.34, p-value < 0.001). FA and track length between allografts with and without rejection, and/or with high vs. low CADI score were not significantly different.

Conclusion: DTI in pediatric kidney transplants is feasible and showed differences in FA and track length values when compared to controls. However, in our limited dataset, DTI did not find differences within the allograft group.

Background: The Society of Pediatric Liver Transplantation (SPLIT) has undergone tremendous growth with > 45 sites contributing data focusing on improving outcomes in pediatric liver transplantation (LT). We report and compare outcomes from the SPLIT Registry.

Methods: Patients < 18 years with first-time LT only enrolled into the SPLIT Registry between 2011 and 2023 were included. Data was stratified into eras from the last published registry update (era 1: 2011-2018, era 2: 2018-2023).

Results: Three thousand five hundred four participants from 47 centers were included (era 1: n = 2159; era 2: n = 1345). Age distribution differed with more children < 1 year. of age at LT in era 2 (era 1: 29% vs. era 2: 33%, p = 0.01). Indications for LT were similar, with biliary atresia (38.8%) and metabolic disease (16.0%) being most common. Exception point use was higher in era 2 (era 1: 45% vs. era 2: 56%, p < 0.001). No difference in graft type (deceased: 81% era 1 vs. 78% era 2, p = 0.78), patient survival at 90 days (era 1: 98.7% vs. era 2: 98.3%), 1 year (era 1: 97.2 vs. era 2: 96.8%), or 3 years (era 1: 95.3% vs. era 2: 95.2%) was noted. Rate of hepatic artery thrombosis was lower in era 2 (era 1: 7% vs. era 2: 5%, p = 0.02).

Conclusions: Trends in pediatric LT within SPLIT note similar LT indications and graft type, higher utilization of exception points, and lower HAT rates despite transplanting more children < 10 kg. This data underscores the evolution of pediatric LT toward higher survivability and overall patient outcomes.

Background: Waitlist mortality remains a critical issue for pediatric heart transplant (HTx) candidates, particularly for candidates with congenital heart disease. Listing center organ offer acceptance practices have been identified as a factor influencing waitlist outcomes. We utilized machine learning (ML) to identify factors associated with waitlist mortality, combining variables associated with institutional offer acceptance practices as well as candidate-specific risk factors.

Methods: We analyzed the Organ Procurement and Transplantation Network database for pediatric HTx candidates listed between 2010 and 2020. Various statistical and ML models were employed to identify predictors of waitlist mortality or clinical deterioration leading to waitlist removal. The dataset was split into training (82%) and testing (18%), and the final model was selected based on predictive performance. SHAP values were used to assess variable importance.

Results: Among 5523 pediatric candidates, overall waitlist mortality was 9.8%. The CatBoost model achieved the highest predictive performance with an AUC-ROC score of 0.74 and a recall score of 0.75. Key predictors included candidate diagnosis, age/size, ventilator use, eGFR, serum albumin, ECMO, and institutional factors such as high offer refusal rates and low transplant volume.

Conclusions: Institutional organ offer acceptance practices influence waitlist outcomes for pediatric HTx candidates. Centers with higher organ refusal rates are associated with worse outcomes, independent of candidate-specific risk factors, underscoring the need for standardizing organ acceptance criteria across institutions to reduce variability in decision-making and improve waitlist survival. Additionally, addressing modifiable risk factors such as malnutrition and renal dysfunction could further optimize patient outcomes.

Background: This case report describes a 10-year-old male with a history of kidney transplantation who developed trichodysplasia spinulosa (TS), a rare skin disorder associated with immunosuppression.

Methods: The patient's condition, characterized by follicular papules and keratinous spines primarily on the face, was managed by a multidisciplinary team.

Results: Treatment involved reducing immunosuppression and administering topical cidofovir alongside oral leflunomide, leading to significant clinical improvement over several months.

Conclusions: This case adds to the literature of TS management and highlights the importance of multidisciplinary care as well as the challenges of treatment accessibility due to insurance limitations.

Background: Education and enhancing the knowledge of adolescents who will undergo kidney transplantation are among the primary objectives of their care. While there are specific interventions in place to achieve this, they require extensive resources. The rise of large language models like ChatGPT-3.5 offers potential assistance for providing information to patients. This study aimed to evaluate the accuracy, relevance, and safety of ChatGPT-3.5's responses to patient-centered questions about pediatric kidney transplantation. The objective was to assess whether ChatGPT-3.5 could be a supplementary educational tool for adolescents and their caregivers in a complex medical context.

Methods: A total of 37 questions about kidney transplantation were presented to ChatGPT-3.5, which was prompted to respond as a health professional would to a layperson. Five pediatric nephrologists independently evaluated the outputs for accuracy, relevance, comprehensiveness, understandability, readability, and safety.

Results: The mean accuracy, relevancy, and comprehensiveness scores for all outputs were 4.51, 4.56, and 4.55, respectively. Out of 37 outputs, four were rated as completely accurate, and seven were completely relevant and comprehensive. Only one output had an accuracy, relevancy, and comprehensiveness score below 4. Twelve outputs were considered potentially risky, but only three had a risk grade of moderate or higher. Outputs that were considered risky had an accuracy and relevancy below the average.

Conclusion: Our findings suggest that ChatGPT could be a useful tool for adolescents or caregivers of individuals waiting for kidney transplantation. However, the presence of potentially risky outputs underscores the necessity for human oversight and validation.

Background: Frailty is a phenotype of cumulative decline leading to decreased physiologic reserve and vulnerability to stressors. Frailty is associated with adverse outcomes after liver transplantation (LT) in adults, but similar data are not available in children. A prospective multicenter study previously determined that frailty is present in 46% of children with end-stage liver disease (ESLD). We utilized this cohort to evaluate the impact of pre-transplant frailty on post-LT outcomes.

Methods: The study included pediatric participants from the original frailty study across 10 North American transplant centers who had subsequently undergone LT. Clinical outcomes were collected up to 1 year post LT. Participants were stratified by their pre-transplant frailty score (defined by a pre-LT frailty score of ≥ 6.0) and long-term outcomes were compared between groups.

Results: 28 (60.7% female, 46.4% biliary atresia) pediatric LT recipients were included, and 54% of children met criteria for frailty (n = 15). Baseline characteristics were comparable between groups; however, those with frailty were significantly more likely to have pre-transplant failure to thrive (33.3% vs. 0%, p = 0.044). Thirty-four hospital readmissions (22 in frail and 12 in non-frail children) occurred in 20 patients. Higher pre-transplant frailty scores were also significantly associated with an increased number of readmissions after transplantation (p = 0.034).

Conclusions: Pediatric frailty may be associated with the adverse outcome of increased frequency of hospitalization in the first year after pediatric liver transplantation. These data support the concept that frail children should be identified and targeted for prehabilitation prior to LT.