Pediatric Transplantation最新文献

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.

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.

Transition of care from pediatric to adult providers occurs during a time of increased risk, especially in the liver transplant population where close follow-up and adherence to immunologic therapies are critical to patient and graft survival. While there is a substantial body of literature supporting the need for improved transition from pediatric to adult care, concrete steps on how to implement a clinic and partner with adult colleagues are lacking. This article aims to provide a flexible pathway for transition clinics that can be tailored to an institution's unique needs while also advocating for system-wide change to better support transitions in care, specifically through the lens of the United States health care system.

Background: Cardiac allograft vasculopathy (CAV) is the leading cause of late graft loss in children after pediatric heart transplantation (HTx). Coronary angiography, the reference standard for diagnosis, is invasive and carries a risk of complications. Noninvasive echocardiographic methods to reliably identify CAV in children have not yet been defined.

Methods: This study assessed the utility of functional echocardiography (FE) in the diagnosis of CAV in children. We prospectively assessed all children (< 18 years old) post-HTx during routine clinical surveillance between 2005 and 2020. For this study, we compared patients diagnosed with CAV (angiographic ISHLT criteria) with transplanted children without CAV, with FE at the time of diagnosis (d-CAV) and 6-12 months before diagnosis (pre-CAV), and evaluated clinical risk factors.

Results: We identified 10 children with CAV and 11 matched controls (CON). Right ventricular longitudinal strain (RV LS) and strain rate (RV LSR) were reduced at d-CAV (d-CAV RV LS, 12.1% [9.2,16.1] vs. CON RV LS, 21.5% [18.2,25.7]; d-CAV RV LSR, 0.75%/s [0.48, 0.98] vs. CON RV LSR, 1.35%/s [0.95,1.50], p < 0.01 for all) and pre-CAV (pre-CAV RV LS, 17.3% [10.8,20.2] vs. CON RV LS, 21.5% [18.2,25.7]; pre-CAV RV LSR 0.95%/s [0.80,1.10] vs. CON RV LSR, 1.35%/s [0.95,1.50], p ≤ 0.05 for all). Patients with CAV were more likely to have class II donor-specific antibodies (p = 0.01).

Conclusion: Right ventricle systolic strain parameters were reduced as early as 12 months prior to CAV diagnosis, while the left ventricle functional parameters remained preserved. FE of the right ventricle may be a useful noninvasive tool for early recognition of developing CAV in transplanted children.

Background: Filamin A (FLNA) deficiency is a known cause of progressive lung disease and need for pediatric lung transplant; however, what may be less well known to lung transplant providers are the extrapulmonary complications of FLNA deficiencies, such as wandering spleen. We present a patient who underwent a lung transplant for FLNA deficiency and later developed posttransplant abdominal pain.

Case presentation: An 11-year-old female who had previously undergone a bilateral lung transplant due to FLNA deficiency, causing progressive lung disease, presented with abdominal pain and diarrhea. The patient's stool was tested for causes of gastroenteritis using a gastrointestinal pathogen panel (GIPP). Additionally, an initial abdominal ultrasound was obtained to rule out surgical causes of acute abdomen. The initial abdominal ultrasound showed the spleen in the correct anatomical location. However, subsequent abdominal ultrasounds revealed an incidental finding of wandering spleen in multiple locations in the abdomen. As she has remained stable despite the migration of her spleen, the decision was made not to pursue surgical intervention and to continue monitoring with medical and surgical follow-up.

Conclusions: There are multiple complications caused by FLNA deficiency besides progressive respiratory failure, which include gastrointestinal (GI) complications such as wandering spleen. Wandering spleen is a rare clinical entity and, to our knowledge, this is the first case report of it being identified in a pediatric lung transplant patient. This case highlights the importance of transplant providers remaining vigilant when evaluating seemingly benign complaints such as abdominal pain in this population.