Pediatric Transplantation最新文献

Pulmonary hypertension (PH) is a potentially life-threatening disorder characterized by abnormalities of the pulmonary vasculature, causing elevated pulmonary artery pressures, which can result in right ventricular dysfunction. Patients with suprasystemic right ventricular pressure unresponsive to aggressive medical therapy have limited treatment options, including balloon atrial septostomy, reverse Potts shunt, or lung transplantation. The decision to proceed to a palliative reverse Potts shunt or lung transplantation, and the choice of one or the other, depends on surgical, medical, and psychosocial factors. In this manuscript, we discuss the definition, pathophysiology, and current treatments for PH in relation to pediatric lung transplantation, including referral indications and special considerations for transplant candidates. We review the reverse Potts shunt as a palliative option for patients with severe PH, discussing indications, patient outcomes, surgical techniques, and the relative risks/benefits compared to lung transplantation. Finally, we propose an algorithm to assist pediatric cardiologists, pulmonologists, intensivists, surgeons, and other healthcare providers in the decision-making between a palliative reverse Potts shunt procedure and lung transplantation for patients with severe PH based on currently available data.

Background: Phosphomannomutase-2 congenital disorder of glycosylation (PMM2-CDG) is the most common congenital disorder of glycosylation, affecting protein glycosylation across multiple organ systems. Hepatic involvement may range from isolated elevations in liver transaminases to end-stage liver disease. Reported outcomes of liver transplantation as a treatment modality are sparse.

Case report: We describe one of the first reported cases of liver transplantation in a child with PMM2-CDG and interim post-transplant outcomes. This patient was diagnosed at 4 months of age after presenting with failure to thrive, lipodystrophy, hypotonia, developmental delay, elevated transaminases, hypoalbuminemia, and coagulopathy. He developed cirrhosis and portal hypertension as well as sequelae of poor protein glycosylation. All these included coagulopathy, protein-losing enteropathy, and refractory ascites requiring serial intravenous fresh frozen plasma and furosemide. He ultimately underwent a liver transplant, after which his ascites resolved. Post-transplant, he developed new-onset recurrent pericardial effusions, suspected to be from a viral etiology versus extrahepatic manifestations of PMM2-CDG, and elevated transaminases following transplantation.

Discussion/conclusions: Liver transplantation may offer clinical benefit in PMM2-CDG with severe hepatic involvement, including resolution of ascites and improved quality of life, due to its potential to restore liver glycosylation function. However, this is only a partial correction as persistent extrahepatic manifestations underscore the need for further research into transplant outcomes and systemic disease progression in CDG.

Background: Hemophagocytic lymphohistiocytosis (HLH) is a rare complication of solid organ transplantation and is a syndrome of systemic hyperinflammation secondary to dysregulation of the inflammatory response, primarily involving lymphocytes and macrophages. It is often fatal and therefore early recognition and treatment are crucial. Among 11 adult cases of HLH in post-lung transplant cases found in the literature, only one patient survived.

Case: We report the first known pediatric case of HLH following lung transplantation. The patient, a previously healthy adolescent, developed end-stage bullous lung disease secondary to acute respiratory distress syndrome (ARDS) and underwent bilateral lung transplantation. Two months posttransplant, he was admitted with an asymptomatic febrile illness of unclear etiology. By day four, evolving multiorgan dysfunction raised concern for HLH. Despite extensive infectious, autoimmune, and malignancy workups, no definitive trigger was identified. Treatment was initiated with dexamethasone monotherapy with subsequent clinical improvement and discharge 1 month later.

Conclusion: Solid organ transplantation appears to raise a patient's risk of developing HLH, although the underlying mechanisms are unclear. Literature review suggests patients are most likely to develop this complication within the first few months of transplantation, and a high index of suspicion must be maintained in those who present with a febrile illness of unclear etiology. Standard HLH treatment protocols may not be applicable to this patient population, and further studies are needed.

Solid organ transplantation (SOT) is a life-saving intervention for pediatric patients with end-stage organ failure. Due to the limited availability of pediatric donor organs, organs from older donors are frequently utilized, increasing the risk of age-mismatched transplants. Older donor organs are linked to heightened immunogenicity, rejection rates, and impaired long-term outcomes. Emerging evidence suggests that aged donor organs may transfer senescence to pediatric recipients, accelerating aging-like processes such as frailty, cognitive decline, and organ dysfunction. Additionally, the induction of senescence could alter pediatric conditions like chronic kidney disease (CKD), juvenile idiopathic arthritis (JIA), and pediatric brain tumors which have been linked to augmented senescence. Animal models have shown that older donor organs induce senescence-associated changes in young recipients, including immune dysfunction and physical and cognitive impairments. This review highlights the role of cellular senescence in pediatric organ transplantation and discusses strategies to mitigate its impact. Therapies targeting senescence, such as senolytics, offer a potential approach to improve outcomes in pediatric recipients. Further research is needed to validate these findings in human studies and guide clinical strategies that expand the donor pool while prioritizing age-matched transplantation for pediatric patients.

Background: Monoclonal antibodies, including rituximab and daratumumab, play a pivotal role in the management of antibody-mediated rejection (AMR) following solid organ transplantation. Although generally effective, these agents can induce rare but potentially fatal complications.

Methods: We present two cases of post-transplant AMR in which patients developed fatal complications following the administration of rituximab and daratumumab. Both cases were analyzed in detail to assess the sequence of clinical events and potential underlying mechanisms.

Results: Both patients developed severe flash pulmonary edema shortly after receiving the monoclonal antibody therapy. This was followed by rapid clinical deterioration, including multiorgan failure. The clinical features and biopsy findings were consistent with cytokine release syndrome as the probable trigger for these complications.

Conclusion: Early recognition, prompt discontinuation of the offending agent, and targeted therapeutic interventions are crucial to improving outcomes in these life-threatening scenarios.

Background: Clostridioides difficile infection (CDI) poses a significant risk to pediatric hematopoietic stem cell transplant (HSCT) due to microbiome disruption, mucosal injury, and graft versus host disease (GVHD). While oral vancomycin prophylaxis (OVP) is effective for preventing recurrent CDI, evidence for its role in preventing initial infection is limited. Our institution employs empiric OVP during the first HSCT admission to prevent initial CDI.

Objectives: We sought to describe the incidence of CDI among pediatric HSCT recipients receiving OVP and to evaluate secondary outcomes related to OVP exposure.

Methods: We conducted a single center, retrospective observational study of 84 pediatric HSCT recipients at our institution receiving OVP during their initial transplant admission. Chart review captured demographics, transplant information, and clinical outcomes. The primary outcome was CDI incidence during hospitalization. Secondary outcomes included VRE infections, refractory CDI following cessation of OVP, and acute GI GVHD.

Results: Only one patient developed CDI (1.19%) while on OVP, despite universal exposure to high-risk antibiotics among the entire cohort. No VRE infections were observed. Rates of GI aGVHD were consistent with national averages. Nine patients (10.7%) developed CDI after discontinuing OVP, all managed with standard treatment.

Conclusion: Empiric OVP during pediatric HSCT hospitalization was associated with a markedly low CDI incidence. Despite theoretical risks of microbiome disruption, no adverse effects were identified in this cohort, including long-term follow-up beyond 5 years. These findings support the safety and potential efficacy of OVP as primary CDI prophylaxis in pediatric HSCT patients.

Background: Schimke Immuno-Osseous Dysplasia Is a Rare Autosomal Recessive Multisystem Disorder Caused by Biallelic Pathogenic Variants in the SMARCAL1 Gene, Which Encodes a DNA Annealing Helicase Essential for Replication Fork Stability and Genomic Maintenance. Loss of SMARCAL1 Function Leads to Genomic Instability, Resulting in a Characteristic Clinical Triad of Disproportionate Short Stature, Steroid-Resistant Nephrotic Syndrome and Immunodeficiency. Kidney Transplantation Is the Standard Treatment for End-Stage Renal Disease in Schimke Immuno-Osseous Dysplasia. However, the Underlying Genomic Fragility and Immunodeficiency Heighten the Risk of Post-Transplant Complications, Particularly Epstein-Barr Virus-Associated Post-Transplant Lymphoproliferative Disorder.

Method: We Report the Case of a 7-Year-Old Girl With Genetically Confirmed Schimke Immuno-Osseous Dysplasia Who Developed Epstein-Barr Virus-Positive Diffuse Large B-Cell Lymphoma Eight Months Following Maternal Kidney Transplantation, Despite Reduced-Intensity Immunosuppression. Rituximab Therapy Resulted in Complete Remission, but Required the Withdrawal of all Immunosuppressive Agents, Thereby Posing a Risk of Kidney Graft Loss.

Result: In the Context of Primary Immunodeficiency and the Development of Post-Transplant Lymphoproliferative Disorder in Such a Setting, the Patient Subsequently Underwent Haploidentical Hematopoietic Stem Cell Transplantation From the Mother, Using an αβ T-Cell-Depleted Graft and a Nephrotoxicity-Sparing Conditioning Regimen. Full Donor Chimerism Was Achieved by Day 28. Immune Reconstitution Occurred Within One Year. At 27 Months After Hematopoietic Stem Cell Transplantation She Remains in Remission With Preserved Kidney Function and no Ongoing Immunosuppression.

Conclusion: This Case Highlights the Feasibility of Haploidentical Hematopoietic Stem Cell Transplantation as a Curative Salvage Strategy for Immunosuppression-Free Survival After Kidney Transplantation in Patients With Schimke Immuno-Osseous Dysplasia.

Introduction: Machine perfusion (MP) can help expand the donor pool, yet its use in pediatric liver transplantation (LT) has been limited. We aimed to compare the characteristics and outcomes of children undergoing LT with vs. without MP.

Methods: We retrospectively compared children (< 18 years) undergoing first LT with vs. without MP using United Network for Organ Sharing data (01/01/2016-12/31/2024). The MP group was compared to all non-MP and to propensity score matched non-MP LT recipients.

Results: Forty MP LT recipients were compared to 3857 all non-MP and 40 matched non-MP recipients. Compared to all non-MP recipients, MP recipients had a higher laboratory MELD/PELD score (median 16.5 vs. 12.0, p = 0.03) and were more likely to receive split grafts (42.5% vs. 21.6%, p = 0.001) allocated at a national level (65.0% vs. 40.8%, p = 0.007) from older donors (median 16.0 vs. 11.0 years, p < 0.001) with longer organ preservation times (median 15.0 vs. 6.5 h, p < 0.001). Although not statistically different, DCD liver grafts were used in 20.0% of MP LTs compared to 11.1% of all non-MP LTs (p = 0.08). Compared to matched non-MP recipients, MP recipients were more likely to have ascites (47.2% vs. 19.4%, p = 0.02). There was no significant difference regarding patient or graft survival between the MP and all non-MP (p = 0.68 and p = 0.80) or the matched non-MP groups (p = 0.28 and p = 0.14).

Conclusion: MP can support LT in sick pediatric recipients using split grafts, while allowing for prolonged preservation times and national-level allocation at a larger radius, without impacting survival.