Pediatric Transplantation最新文献

Background: Florida Pediatric Bone Marrow Transplant and Cell Therapy Consortium (FPBCC) was formed in 2018 by five pediatric transplant programs in Florida. The key objectives of the consortium are to improve outcomes for children undergoing HSCT through collaboration among centers, data sharing, implementation of best practices, QI projects, and prospective clinical trials. The first step in that process was to analyze HSCT outcomes from all participating centers and identify areas for improvement. In this report, we describe the effectiveness of the activities of this consortium, focused on improving patients' outcomes.

Methods: A retrospective data review of allogeneic transplant 1-year survival, obtained from the annual CIBMTR report, from the five FPBCC centers was compared to survival from 38 other pediatric centers in the country over two periods: preconsortium establishment, from 2016 to 2018, and postconsortium establishment, from 2019 to 2021. Of the 38 other pediatric centers, 22 were defined as small, similar to consortium centers by number of transplants (20-70 first allogeneic transplants per center in a 3-year period) and 16 were larger centers (> 71 first allogeneic transplants per center in a 3-year period).

Results: The 1-year posttransplant survival for the FPBCC centers significantly improved from 77.5% (2016-2018) to 89.5% (2019-2021; p = 0.0313). During the same respective time periods, other small centers improved from 82.4% to 87.9% (p = 0.0059), and large centers maintained stable survival at 85.6%-85.4% (p = 0.2676).

Conclusions: There was a substantial improvement in the 1-year survival of allogeneic transplant recipients treated in FPBCC centers, achieved after the initiation of consortium activities. Within a 3-year period, consortium centers, which had a lower starting point, reached 1-year survival comparable to that of other small and large centers. A significant improvement in survival, although a lesser percentage of change, was seen in other programs of similar size across the country, but not in larger programs. We consider that the magnitude of improvement in survival (12% points or 4% per year), which was not seen among other programs, attests to the effectiveness of consortium activities. A blueprint for improvement in outcomes established by the FPBCC can be shared with other programs around the world that strive to improve posttransplant survival.

Background: Heart transplantation in teenagers has not been well studied. Teenage recipients have unique considerations that influence outcomes-complexity of cardiac disease, wide range of donor sizing and age, mechanical support options, and medication nonadherence. We sought to analyze the outcomes of heart transplantation in teenagers, focusing on sex-based disparities.

Methods: The United Network for Organ Sharing dataset was queried for patients 13 to 19 years of age who underwent heart transplantation from 2002 to 2021. Patients were divided into two groups based on sex. Baseline clinical characteristics were compared, along with an analysis of survival data. The primary outcome of interest was freedom from death or retransplantation.

Results: Heart transplantation was performed in 2320 teenagers; 812 (35.0%) were female. Female recipients were smaller (54.0 vs. 62.0 kg, p < 0.0001) and less likely to have congenital heart disease (26.5 vs. 31.6%, p < 0.0001). Female patients also had fewer pre-transplant ventricular assist devices (24.7 vs. 32.2%, p = 0.0002). By multivariable analysis, female sex was independently associated with lower survival (HR 1.26 [CI 1.08-1.48], p = 0.003). Sex-mismatched female recipients had significantly lower survival than sex-matched male recipients (HR 1.29 [CI 1.06-1.58], p = 0.009). Donor: recipient age difference < 5 years and donor: recipient weight > 1.2 were independent predictors of higher survival (p < 0.05).

Conclusions: Female teenagers have lower survival following heart transplantation than their male counterparts. Male donor-female recipient transplants have the lowest survival among sex-matching groups. The use of organs from oversized or younger donors in teenagers may be considered to help improve post-transplant survival.

Background: Cranioectodermal dysplasia (CED) is a rare ciliopathy that causes mortality through its impact on liver and kidney dysfunction. To date, there has only been a single report of a successful kidney-liver transplant in a pediatric patient with CED.

Case presentation: We present a pediatric patient who received a sequential liver-kidney transplant due to progressive organ dysfunction caused by CED. At the age of 7, the patient underwent a liver transplant, followed sequentially by a kidney transplant 5 years later. We provide a 3-year follow-up to the kidney transplantation.

Results: The liver transplant was complicated by a portal vein stricture causing portal hypertension, which required revision. The patient had no complications from the kidney transplant despite comorbidities related to the CED diagnosis, such as thrombocytopenia.

Conclusions: We discuss the viability of the sequential liver-kidney transplant for patients with CED and suggest that physicians consider this sequence if their patients with CED present with corresponding sequential organ failure.

Background: The Fontan operation is widely regarded as a highly successful and effective palliative measure for many congenital heart diseases. However, among patients who undergo Fontan procedures, Fontan failure inevitably occurs in some cases, giving rise to various complications, including protein-losing enteropathy, plastic bronchitis, refractory arrhythmia, and coagulopathy. When Fontan fails, heart transplantation emerges as one of the treatment options.

Methods: This retrospective study examines the outcomes of heart transplantation in 10 patients experiencing Fontan failure over a span of 23 years at a single institution.

Results: The statistical analysis reveals survival rates of 80.0%, 60.0%, and 33.3% at 1, 3, and 5 years posttransplantation, respectively. Moderate or severe atrioventricular valve regurgitation (AVVR) emerges as a risk factor for posttransplantation mortality. Additionally, pretransplant atrial tachycardia is identified as a risk factor for early mortality following heart transplantation.

Conclusions: Moderate or severe AVVR is a risk factor for posttransplantation mortality in patients with Fontan circulation failure, while pretransplant atrial tachycardia is a risk factor for early mortality after cardiac transplantation.

Background: Liver transplantation (LT) is the standard therapy for end-stage liver disease. Liver allografts are at risk for fibrosis, for which biopsy is the gold standard for evaluation but carries risks. There is a need for noninvasive modalities to track the trajectory of fibrosis.

Methods: We evaluated the diagnostic accuracy of shear wave elastography (SWE) liver stiffness (LS) measurements to quantify fibrosis in pediatric liver transplant recipients.

Results: Between 2007 and 2024, 93 patients had 106 liver biopsies performed within 13 months of elastography. LS values were significantly higher in patients with moderate (F2-3) fibrosis compared to those with no significant fibrosis (F0-1) (7.5 ± 0.48 kPa vs. 6.09 ± 0.18 kPa, p = 0.0015). LS values were significantly higher in patients with moderate fibrosis compared to those with no significant fibrosis in both whole (8.4 ± 0.95 kPa vs. 6.6 ± 0.54 kPa, p = 0.02) and segmental allografts (7.1 ± 0.52 kPa vs. 5.9 ± 0.17 kPa, p = 0.02). There was no significant difference in LS values according to allograft type or donor status. The AUROC for LS measurements was 0.71, indicating a good discriminative ability between no significant and moderate fibrosis. A cut-point of 6.09 kPa for SWE was identified, distinguishing between no significant and moderate fibrosis (sensitivity of 81%). A SWE cut-point of 10.40 kPa had a high specificity of 99% in determining moderate fibrosis.

Conclusion: We demonstrated a significant association between biopsy fibrosis and SWE LS values and conclude that SWE provides a noninvasive option for monitoring liver a fibrosis.

Background: X-linked chronic granulomatous disease (X-CGD) may be associated with McLeod syndrome (MLS) as a contiguous gene deletion syndrome. MLS is characterized by the loss of XK protein along with Kx antigen on red blood cell (RBC) surfaces and late-onset neurocognitive symptoms. RBCs in healthy donors express XK protein and related Kx antigen on the surface; therefore, transfusion from random donors to patients with MLS poses a risk of Kx sensitization, leading to severe hemolysis. As the radical treatment of X-CGD is hematopoietic cell transplantation (HCT), treating patients with coexisting X-CGD and MLS is extremely challenging.

Method: A retrospective chart review was completed for a case of X-CGD associated with MLS who underwent HCT.

Result: A 7-year-old boy with X-CGD and MLS underwent HCT from a matched unrelated donor (human leukocyte antigen, 7/8 matched). Rituximab was added to busulfan-based reduced intensity conditioning to prevent Kx sensitization. Donor RBCs were depleted from the bone marrow before infusion to prevent Kx sensitization. Neutrophil engraftment was achieved on day +19 with full donor chimerism. No hemolytic events occurred, and he is living well 2 years after HCT.

Conclusion: We were able to safely perform transplantation in a patient with X-CGD and MLS by adding rituximab and depleting RBCs from the donor bone marrow. The long-term impact of HCT on MLS is unclear. However, HCT may improve prognosis and quality of life by reducing recurrent infections caused by X-CGD. Moreover, this HCT method is non-invasive, relatively simple, and easily implementable.

Background: Pediatric Acute Liver Failure (PALF) frequently requires liver transplantation (LTx). The neurological condition can deteriorate rapidly, but the difficulty in assessing the (ir)reversibility of neurological symptoms can hamper therapeutic decision-making, including transplantation. We aimed to determine the association between pupillary reflexes (PR), brain stem reflexes (BSR), radiological signs of brain herniation, and subsequent neurological outcome.

Methods: We analyzed a retrospective, observational cohort of PALF patients with severe hepatic encephalopathy (grade III-IV), admitted to our national pediatric liver transplantation center between 1993 and 2023. We subdivided the patients into groups with PR present or PR absent. We compared the two groups for pre-treatment neurological and neuro-radiological parameters and related the findings to neurological outcomes.

Results: Survival rate in patients with PR present was higher compared to patients with PR absent [70% (26/37) and 29% (4/14); resp., p = 0.008]. In the absence of PR, neurological outcome could still be favorable after LTx (n = 3/6). Presence or absence of BSR was not related to the outcome in terms of survival or death. Radiologically proven brain herniation was associated with mortality (6/7) or minimally conscious state (1/7), irrespective of undergoing a LTx or not.

Conclusions: Although absence of PR is associated with a poor prognosis, the neurological outcome can still be favorable after LTx. Radiological signs of brain herniation are strongly associated with mortality or severe neurological outcomes, irrespective of subsequent transplantation. We therefore advocate that absence of PR should be an indication for radiological imaging to assess brain herniation before making major treatment decisions.

Background: Medication adherence and timing of doses remains a challenge for adolescent patients following heart transplant. Mobile technology and adherence promotion efforts offer new avenues for direct observation of medication adherence and timeliness of medication-taking behavior. The study explores posttransplant medication maintenance, highlighting the importance of consistent dose timing with tacrolimus. The use of directly observed therapy (DOT) via a mobile health app was examined as a method for real-time medication monitoring, offered a platform for patients to upload videos of themselves taking medication for review by transplant team members.

Methods: The study examined a single-group design involving 10 adolescent heart transplant recipients over a 12-week DOT intervention, assessing both medication adherence and post-intervention outcomes.

Results: Results from multilevel regression models analyzing inter-dose timing and deviation from 12-h intervals revealed significant variability among patients and a correlation between increased deviation from the 12-h dose interval and both older patients and those with greater perceived barriers to medication adherence.

Conclusions: Findings suggested a link between deviation from recommended dose timing and poorer posttransplant health outcomes. Findings underscored the potential of DOT and mobile health to examine timeliness of medication adherence, to directly observe medication-taking behavior, and association with posttransplant health outcomes.

Background: Immunosuppression is paramount to prevent acute rejection in solid organ transplant but also poses a risk for infection and malignancy. Identifying factors that influence rejection may allow for personalization of treatment and avoidance of an unnecessary degree of immunosuppression for the vulnerable pediatric population.

Methods: We conducted a retrospective review analyzing public data provided by the Organ Procurement and Transplantation Network for pediatric patients listed for solid organ transplantation (kidney, liver, lung, and heart) from March 1998 to December 2022. Univariate and multivariate logistic regression was used to identify independent risk factors for treated acute rejection at 6 months and/or 1 year for liver, lung, kidney, and heart transplants.

Results: The study population consisted of the following pediatric patients for each organ studied: liver (n = 8993), lung (n = 846), heart (n = 7118), and kidney (n = 14 600). At 1 year, 28.4% and 31.7% of males and females, respectively, were treated for rejection in liver transplant, 24.1% and 34.5%, respectively, for lung, 14.8% and 16.2%, respectively, for kidney, and 25.2% for both in heart transplant. In multivariate analysis, male recipient status was a statistically significant protective factor against rejection in liver transplant, OR = 0.85 (p < 0.001), lung transplant, OR = 0.61 (p = 0.004), and kidney transplant, OR = 0.91 (p = 0.040), but not heart transplant, OR = 0.96 (p = 0.460).

Conclusions: Our study demonstrates that pediatric males may have a lower risk of acute rejection in liver, lung, and kidney transplant yet not in heart transplant. These findings may have implications for the level of maintenance immunosuppression for pediatric male transplant recipients.

Background: Toxoplasma gondii can cause opportunistic infections leading to life-threatening disseminated disease after organ transplantation. However, there is a paucity of pediatric-specific data to guide recommendations for the prevention of toxoplasmosis after solid organ transplantation.

Methods: To assess current practices, international pediatric transplant providers were surveyed.

Results: Considerable variability in both screening and prophylaxis strategies was found across centers and organ types, with heart transplant programs performing more screening and prophylaxis. Trimethoprim/sulfamethoxazole was the preferred prophylaxis agent for each graft; no toxoplasmosis cases were recalled while patients received prophylaxis.

Conclusion: More research is needed to clarify and standardize the optimal toxoplasmosis prevention strategy.