Pediatric Transplantation最新文献

Background: Early studies evaluating steroid-minimization (SM) employed immunosuppression that is not representative of the modern era of immunosuppression. We hypothesized that current SM-based immunosuppression protocols offer unique advantages for pediatric kidney transplant recipients (pKTR) without compromising allograft and patient outcomes.

Methods: This is a retrospective study of 3263 pKTR between 2000 and 2019 from the North American Pediatric Renal Trials and Collaborative Studies (NAPRTCS). Study participants were grouped as SM and steroid based (SB) based on corticosteroids use at 30 days post-transplant. Primary outcomes of interest were allograft function and survival. Secondary outcomes included linear growth, obesity and hypertension.

Results: A SB regimen was used in 2312 (70.9%) and SM in 951 (29.1%). Comparison of the allograft function showed that SM was associated with a significantly higher estimated glomerular filtration rate (eGFR) at 1, 2, and 3 years post-transplant compared to SB. Kaplan-Meier curves showed that SM was associated with significantly less allograft loss (p = 0.01) compared to SB while there was no significant difference in allograft survival when stratified by induction and steroid regimen (p = 0.49). Multivariate Cox regression showed that the SB regimen was not associated with improved graft survival (hazard ratio 1.38 [0.89-2.16]; p = 0.15). Secondary outcome analysis showed significantly better linear growth and less obesity and hypertension in SM compared to SB.

Conclusions: SM immunosuppression was not associated with decreased allograft rejection, function or survival, and was associated with a reduced risk of secondary complications. In patients receiving contemporary, tacrolimus-based maintenance immunosuppression, a SM regimen may be preferred.

Background: The use of romiplostim, a thrombopoietin agonist, has increased in the last decade for the treatment of immune mediated thrombocytopenia and severe aplastic anemia. Its utility has been explored in the management of delayed platelet engraftment and secondary platelet failure during stem cell transplant (SCT), but its use has remained largely anecdotal in pediatric allogeneic SCT.

Methods: In this single centre, retrospective study we report the largest pediatric SCT cohort use of romiplostim.

Results: Romiplostim was used in 17 children for several indications, principally including poor graft function (PGF) and immune-mediated cytopenia (IMC), including multi-lineage cytopenia. The overall response rate (ORR) was 76.5% and the median time to achieve OR was 42 days. No toxicity was observed with romiplostim including marrow fibrosis, clonal evolution and thrombosis with a median follow-up of 18 months. Romiplostim averted the need for second allogeneic SCT in two patients with late graft failure and the need for stem cell boost (SCB) in three patients.

Conclusion: We propose that romiplostim can be safely used in the cytopenia in pediatric SCT to good effect.

Background: Hematopoietic stem cell transplantation (HSCT) has become an essential curative strategy for various malignant and non-malignant pediatric diseases. However, HSCT recipients remain highly vulnerable to complications, often requiring pediatric intensive care unit (PICU) admission. Identifying key risk factors and predictors of mortality is crucial for improving patient outcomes. This study aims to evaluate the clinical characteristics, risk factors, and outcomes of pediatric HSCT patients requiring PICU admission, focusing on organ failure, respiratory and cardiovascular dysfunction, and the impact of supportive therapies.

Methods: This retrospective, single-center study included pediatric HSCT recipients admitted to a tertiary PICU between August 2019 and October 2023. Patients with PICU stays shorter than 24 h were excluded. Clinical and demographic characteristics, HSCT-related parameters, PICU admission criteria, and patient outcomes were analyzed. Logistic regression models were applied to identify independent risk factors associated with mortality.

Results: Among 40 HSCT recipients requiring PICU admission, the overall mortality rate was 80%, exceeding previously reported rates. Sepsis, respiratory failure, and multiple organ dysfunction were the primary reasons for admission. Elevated PELOD scores were strong predictors of mortality. All patients requiring mechanical ventilation, inotropic support, or renal replacement therapy died (p < 0.001), whereas all patients managed with non-invasive ventilation survived, underscoring the importance of early and appropriate respiratory support.

Conclusion: Organ failure significantly impacts mortality in pediatric HSCT recipients, emphasizing the need for early intervention and proactive monitoring. Structured post-HSCT surveillance, particularly for patients with prior PICU admissions, is critical for identifying early signs of organ dysfunction and optimizing intensive care management.

Background: The rates of organ transplantation declined during the COVID-19 pandemic as donors testing positive for SARS-CoV-2 on respiratory PCR were ineligible to donate. The implications of this practice are important for patients with limited donor pools, such as pediatric populations. Several case studies have demonstrated non-inferior outcomes in adult patients receiving non-pulmonary organ transplants from COVID-positive adult donors. The feasibility and safety of such a transplant have yet to be established for donors under 1 year of age.

Case presentation: We present two cases of non-pulmonary, solid organ transplantation from donors under 1 year of age testing positive for COVID-19 on respiratory PCR in the absence of respiratory or systemic symptoms. The first patient was a 15-month-old with Wolcott-Rallison Syndrome presenting with congenital diabetes and recurrent hepatitis. The patient underwent a combined liver-pancreas transplant from an 8-month-old donor. Postoperatively, the recipient did not have any complications related to COVID-19 but experienced a self-limited, transient respiratory distress. The second patient was a 5-month-old with methylmalonic acidemia experiencing recurrent metabolic crisis. The patient received a liver transplant from a 3-month-old donor. Immediate postoperative imaging revealed anastomotic thrombosis of the hepatic artery managed with arterial reconstruction.

Conclusion: Our case series is the first to establish the feasibility of non-pulmonary solid organ transplants from a COVID-positive donor under 1 year of age. This is also the first report of a successful combined liver-pancreas transplant from an infant donor. Transplantation from donors with a positive SARS-CoV-2 test may be feasible with adequate serologic testing and postoperative management.

Auxiliary partial orthotopic liver transplantation (APOLT) has evolved from a technical challenge into a sophisticated therapeutic strategy for selected pediatric patients with acute liver failure (ALF) and non-cirrhotic metabolic liver diseases (NCMLD). In ALF, APOLT acts as a temporary bridge to native liver regeneration, offering the unique possibility of complete immunosuppression withdrawal. For patients with NCMLD, the procedure corrects critical metabolic defects while preserving the native liver, positioning it as a biological platform for emerging curative treatments like in vivo gene editing. Historically, the widespread adoption of APOLT was limited by technical challenges, notably portal steal leading to graft atrophy. This review summarizes the evolution of APOLT, detailing its indications, technical refinements, and outcomes; thereby presenting its advanced surgical techniques, such as portal flow modulation and refined anastomotic strategies, that have successfully overcome these risks, achieving outcomes comparable to standard orthotopic liver transplantation in experienced centers. We also highlight innovations like domino-auxiliary procedures and the first successful robotic APOLT, which underscore the procedure's technical progress. The conclusion asserts that APOLT's future is tied to advances in regenerative medicine, especially CRISPR-based gene therapies that may offer a definitive cure. Realizing this potential, however, necessitates a structured global effort to disseminate surgical expertise through mentorship programs and international registries. APOLT now serves as a critical bridge between conventional transplantation and a new era of molecular and regenerative cures for pediatric liver disease.

Background: This is the first reported case of empyema due to Mycoplasma hominis in a pediatric transplant recipient.

Methods: A 16-year-old Indigenous Canadian boy developed acute respiratory distress 29 days post-bilateral lung transplantation for chronic lung disease and pulmonary hypertension secondary to extreme prematurity and an atrial septal defect. Pre-transplant donor bronchial cultures grew Candida albicans and methicillin-sensitive Staphylococcus aureus, so he received 14 days of cefazolin. Post-transplant prophylaxis included azithromycin, voriconazole, micafungin, TMP-SMX, and valacyclovir. Immunosuppression included anti-thymocyte globulin induction, followed by tacrolimus, mycophenolate mofetil, and prednisone. The patient developed a large right pleural effusion over the course of 24 h requiring intensive care and high-flow supplemental oxygen. Pleural thoracentesis revealed a neutrophil-predominant exudative empyema. Routine cultures were negative; M. hominis was detected by PCR and specialized media. The patient completed 28 days of clindamycin and doxycycline and made an uneventful recovery.

Results: M. hominis and Ureaplasma species are donor-derived pathogens that can cause significant morbidity, including sternal wound infection, mediastinitis, pericarditis, and empyema. Post-lung transplant M. hominis infections occur in 2%-5% of cases. Diagnostic challenges, low clinical suspicion, and rising resistance contribute to poor outcomes and inappropriate antibiotic use. Although this patient's ammonia level was normal, hyperammonemia syndrome also remains a rare but serious complication of Ureaplasma urealyticum and M. hominis infections.

Conclusion: Early screening, PCR testing, and prompt combination empiric therapy are crucial for improving outcomes in M. hominis infections.

Background: Pulmonary vein stenosis (PVS) after pediatric heart transplantation (PHT) is an observed phenomenon with previously unknown incidence, risk factors, treatment, and outcome.

Methods: This is a review of three recent publications describing PVS after PHT.

Results: In total, 712 PHT recipients from four centers, over a combined 43 years, are reviewed. Thirty-one new cases of PVS after PHT, in addition to six patients with preexisting PVS, are described. PVS diagnosis occurred in the first year after PHT for most patients. Left-sided PVS were more than twice as common as right-sided PVS. Nearly half (43%) experienced multivessel PVS. Major risk factors of PVS after PHT included younger age, history of congenital heart disease (CHD), and history of anomalous pulmonary venous return. The treatment of PVS after PHT varied, reflecting uncertainty in the management of PVS generally. With a median follow-up of less than 3 years, 19% of patients with PVS after PHT died.

Conclusions: PVS after PHT complicated approximately 4.4% of cases in these reports. PVS is more common after PHT in younger patients with a history of CHD. PVS is generally diagnosed in the first year after PHT. We recommend careful evaluation for PVS in the first year after PHT in patients with known risk factors.

Background: Normothermic regional perfusion (NRP) is gaining rapid popularity in adult donation after circulatory death (DCD) to increase organ utilization and improve outcomes. However, literature is lacking for the pediatric population. We therefore present the youngest DCD donor in the United States from whom a liver was recovered with NRP and subsequently transplanted.

Methods: The donor was a 5-year-old male who underwent thoraco-abdominal NRP for kidney and liver procurement. In total, 72 min passed from the withdrawal of life-sustaining treatment to the start of NRP, resulting in 10 min of functional warm ischemia time. The donor was perfused for 80 min, with lactate levels decreasing from 8.29 at the start of perfusion to 5.40 mmol/L at the end of perfusion. The procured graft weighed 480 g and was subsequently transplanted in an adult female recipient with decompensated cirrhosis due to alcohol-associated liver disease.

Results: The liver was successfully utilized and functioned immediately with no graft-specific complications. The patient was discharged on postoperative day 39.

Conclusions: This case demonstrates that NRP can be applied effectively in small pediatric donors, yielding excellent early graft function. Our experience adds to the emerging literature on pediatric NRP. We conclude that broader adoption of NRP could help increase the donor pool and ease the strain on the pediatric waiting list.

Background: Changes to the calculation of the Kidney Donor Profile Index (KDPI) have lowered the KDPI of hepatitis C (HCV+) donor kidneys; therefore, increasing the proportion of pediatric-prioritized kidneys that are HCV+. We aimed to study consent rates for HCV+ kidneys among pediatric kidney transplant candidates.

Methods: We identified pediatric candidates waitlisted from 2019 to 2024 and excluded those who received a living donor transplant. We used logistic regression to identify candidate characteristics associated with HCV+ offer consent and Cox proportional hazards models to determine the association between HCV+ offer consent and the rate of deceased donor transplantation.

Results: Among 3202 candidates included in the analysis, 124 (4%) consented to receive HCV+ deceased donor kidney offers, and 3077 (96%) did not. In adjusted logistic regression, higher candidate age (OR 1.09 per year, 95% CI 1.03-1.15, p = 0.002) and high PRA status (OR 2.76, 95% CI 1.42-5.37, p = 0.003) were associated with a higher odds of consenting to receive HCV+ donor offers, whereas Hispanic ethnicity was associated with lower odds (OR 0.44, 95% CI 0.28-0.72, p = 0.001) of consenting to receive these offers. 2773 candidates (87%) received a transplant. There was no significant association between HCV+ donor offer consent status and transplant rate after adjusting for candidate characteristics. Only 1 received a kidney from a HCV+ donor.

Conclusions: Consent to receive HCV+ donor kidney offers was rare among pediatric kidney transplant candidates. Allocation changes that increase the proportion of pediatric-prioritized kidneys that are HCV+ may decrease access to transplant for pediatric candidates.

Background: Screening for social needs has become increasingly common across healthcare settings. While pediatric programs across the United States have successfully implemented social needs in a clinic setting, the ability to connect families with a positive screen to needed resources is not entirely clear. Through this quality improvement initiative, we sought to universally screen for social needs and refer all families with a positive screen to community resources.

Methods: Social needs screening was conducted within a pediatric heart transplant clinic in the Western USA. The clinic team devised two separate resource referral pathways: high-risk needs (addressed by social worker) and low-risk needs (referred to Unite Us). Referral outcomes of interest were resource identification and resource connection, with the social worker pathway demonstrating higher effectiveness.

Results: Social needs screening identified 66 active needs among 28 of the 86 families screened. Team members were unable to identify a community resource for almost half of the identified needs (n = 30, 44.8%), most often because a resource was not found (n = 23). Of the 59 needs addressed, the clinic team was able to connect families to resources for 24 needs. Overall, families were connected to resources for 36.4% of all identified needs.

Conclusions: Screening for social needs revealed a high degree of social need. However, referral to resources was hampered by two key barriers-lack of available resources and lack of local program follow-up. When resources were identified, the in-person support and referral pathway was more effective than remote support.