Pediatric Transplantation最新文献

Background: Despite the existence of institutional protocols, liver transplant centers often have variability in early immunosuppression practices. We aimed to measure within-center variability in early immunosuppression after pediatric liver transplant (LT) and examine its association with one-year outcomes.

Methods: We analyzed pediatric LTs from 2013 to 2018 in the United Network for Organ Sharing registry, with data aggregated by center. We categorized induction regimen as corticosteroids only vs. T-cell depleting antibody vs. non-T-cell depleting antibody. Primary exposures were coefficient of immunosuppression variability (CIV) in (1) induction and (2) mycophenolate mofetil (MMF) use. Primary outcomes were one-year graft survival, patient survival, and acute rejection rate within the first year after transplant.

Results: The study cohort included 2542 LT recipients from 67 LT centers. Sixteen centers (24%) had no MMF variability; twenty-five centers (37%) had no induction variability. In multivariable analysis, induction CIV was associated with 2.72 times greater odds of acute rejection in the first year (OR 2.72; 95% CI 1.66-4.45; p < 0.001). MMF CIV was not associated with rejection (OR 1.22, 95% CI 0.66-2.25, p = 0.527). Neither one-year graft nor patient survival were associated with induction or MMF CIV.

Conclusions: Induction CIV is associated with higher one-year acute rejection odds and did not impact short-term graft or patient survival. Improved understanding of the reasons for high CIV will inform future work aiming to determine whether reducing variability may improve outcomes.

Introduction: Cystathionine-β-synthase deficiency (CBSd) is an inherited metabolic liver disease causing morbidities in eyes, skeleton, brain, and vasculature. Despite its potential lethality due to thromboembolism and liver failure, sole diagnosis of CBSd seemed not to fulfill the enlistment criteria for deceased donor liver transplantation in previous reports.

Methods: We retrospectively reviewed three cases of living donor liver transplantation (LDLT) for pediatric CBSd patients responding poorly to conservative treatment in Beijing Friendship Hospital, and a literature review was performed.

Results: Patients 1 and 3 received donated partial liver from heterozygous carrier parents, and Patient 2 received donated partial liver from a CBS-competent parent. Patient 2 developed portal thrombus 1 day after LDLT, which was resolved with surgical thrombectomy and reconstruction. Patients 1 and 3 had their resected liver donated to other patients with advanced liver cancer, and the domino grafts functioned well until the death due to tumor recurrence.

Conclusion: Parental LDLT, whether from carriers or not, is an appropriate alternative for CBSd patients resistant to medical treatment. Risk of peri-operative thromboembolism might be higher in CBSd than in other LDLT cases, and explanted livers with CBSd could serve as domino grafts.

Background: Liver transplantation is the standard therapy for end-stage liver disease in pediatric patients with biliary atresia (BA), congenital and metabolic conditions, and for an unresectable malignant tumor like hepatoblastoma (HB). BA is the leading indication for pediatric liver transplantation, while HB is the most common childhood liver cancer. Despite improved outcomes through advanced surgical techniques and novel immunosuppression, pediatric liver transplantation (pLT) is complicated by post-transplant infections.

Methods: A retrospective review was performed of pLT recipients at Cincinnati Children's Hospital Medical Center (CCHMC) and stratified patients by underlying disease to assess impact on post-transplant infectious events.

Results: BA patients were youngest at pLT (12.5 months; p < 0.001) compared to other disease cohorts (HB 30.8, other 43.7). All HB patients received organs from deceased donors. In the year following pLT, 93% of the patients experienced at least one infectious event (IE). HB patients had the highest mean number of IE across disease groups (5.5 IE/patient vs. BA 4.5, other 4.0; p = 0.055), with significantly more patients with fever and neutropenia (p < 0.001) and EBV infections (p = 0.012). HB patients were more likely to develop IE earlier after pLT than non-HB groups (p = 0.013), especially Clostridioides difficile (p < 0.01) and fever and neutropenia (p < 0.01). Despite having variable IE experiences, 1-and-5-year survival across disease groups were similar.

Conclusions: IE were frequently observed in HB patients after pLT, possibly related to pre-and-postoperative chemotherapy and associated neutropenia. Underlying disease may help inform targeted infection-related patient management following pLT.

Background: Langerhans cell histiocytosis (LCH) is a rare malignant disorder of epidermal antigen presenting cells. It is characterized by infiltration of various tissues with dendritic cells (Langerhans cells, LC) that express CD1a or CD207 (langerin), often leading to organ dysfunction. A patient with LCH required liver transplantation (LT) for LCH-associated biliary-tract disease. Cholangiopathy developed after LT. The question arose: In this patient, did LC in damaged liver-allograft biliary epithelium signify acute cellular rejection (ACR) or recurrent LCH?

Methods: We evaluated immunohistochemical identification of LC (CD1a, CD207) in the proposita and in 14 ACR patient samples as distinguishing between ACR and recurrent LCH.

Results: Among 15 patient samples, 3 (20%) marked with neither antibody. Among the remaining 12 samples (80%), 4 (26.7%)-including that from the proposita-had cells marking for both antigens within bile-duct epithelium as well as in surrounding portal-tract connective tissue, 2 (13.3%) had cells marking for both antigens in one region or the other, but not in both, and 6 (40%) had cells marking for only one antigen in one region or the other.

Conclusions: Immunostaining for CD1a and CD207/langerin in the setting of ACR without suspicion of LCH identifies LC in damaged bile ducts. This biomarker pairing proved not to be LCH-specific. Our findings indicate that the presence of these cells alone is insufficient to identify recurrent LCH in the allograft liver.

Due to the current organ shortage waitlist, alternatives to allotransplantation are necessary. Xenotransplantation is currently being pursued as one such alternative in adults in need of kidney or heart transplantation. Cardiac xenotransplantation of genetically modified pig hearts has been conducted twice in adults under the United States Food and Drug Administration (FDA) expanded access criteria. Because of the shortage of transplantable hearts for children as well as the lack of mechanical circulatory support in this population, pediatric researchers are exploring FDA expanded access in high-risk neonates and infants who lack alternative options for survival. The adult cardiac xenotransplantation experience with expanded access can provide lessons and highlight nuances for researchers preparing pediatric application. This includes aspects of informed consent, biosurveillance, and protection of bystanders from potential xenozoonoses.

Background: Despite early diagnosis and medical interventions, patients with methylmalonic acidemia (MMA) suffer from multi-organ damage and recurrent metabolic decompensations.

Methods: We conducted the largest retrospective multi-center cohort study so far, involving five transplant centers (NCCHD, KUH, KUHP, ATAK, and EMC), and identified all MMA patients (n = 38) undergoing LDLT in the past two decades. Our primary outcome was patient survival, and secondary outcomes included death-censored graft survival and posttransplant complications.

Results: The overall 10-year patient survival and death-censored graft survival rates were 92% and 97%, respectively. Patients who underwent LDLT within 2 years of MMA onset showed significantly higher 10-year patient survival compared to those with an interval more than 2 years (100% vs. 81%, p = 0.038), although the death-censored graft survival were not statistically different (100% vs. 93%, p = 0.22). Over the long-term follow-up, 14 patients (37%) experienced intellectual disability, while two patients developed neurological complications, three patients experienced renal dysfunction, and one patient had biliary anastomotic stricture. The MMA level significantly decreased from 2218.5 mmol/L preoperative to 307.5 mmol/L postoperative (p = 0.038).

Conclusions: LDLT achieves favorable long-term patient and graft survival outcomes for MMA patients. While not resulting in complete cure, our findings support the consideration of early LDLT within 2 years of disease onset. This approach holds the potential to mitigate recurrent metabolic decompensations, and preserve the long-term renal function.

Background: Although the outcomes of living donor liver transplantation (LDLT) for pediatric acute liver failure (PALF) have improved, patient survival remains lower than in patients with chronic liver disease. We investigated whether the poor outcomes of LDLT for PALF persisted in the contemporary transplant era.

Methods: We analyzed 193 patients who underwent LDLT between December 2000 and December 2020. The outcomes of patients managed in 2000-2010 (era 1) and 2011-2020 (era 2) were compared.

Results: The median age at the time of LDLT was 1.2 years both eras. An unknown etiology was the major cause in both groups. Patients in era 1 were more likely to have surgical complications, including hepatic artery and biliary complications (p = 0.001 and p = 0.013, respectively). The era had no impact on the infection rate after LDLT (cytomegalovirus, Epstein-Barr virus, and sepsis). The mortality rates of patients and grafts in era one were significantly higher (p = 0.03 and p = 0.047, respectively). The 1- and 5-year survival rates were 76.4% and 70.9%, respectively, in era 1, while they were 88.3% and 81.9% in era 2 (p = 0.042). Rejection was the most common cause of graft loss in both groups. In the multivariate analysis, sepsis during the 30 days after LDLT was independently associated with graft loss (p = 0.002).

Conclusions: The survival of patients with PALF has improved in the contemporary transplant era. The early detection and proper management of rejection in patients, while being cautious of sepsis, should be recommended to improve outcomes further.

Introduction: The successes in the field of pediatric kidney transplantation over the past 60 years have been extraordinary. Year over year, there have been significant improvements in short-term graft survival. However, improvements in longer-term outcomes have been much less apparent. One important contributor has been the phenomenon of low-level rejection in the absence of clinical manifestations-so-called subclinical rejection (SCR).

Methods: Traditionally, rejection has been diagnosed by changes in clinical parameters, including but not limited to serum creatinine and proteinuria. This review examines the shortcomings of this approach, the effects of SCR on kidney allograft outcome, the benefits and drawbacks of surveillance biopsies to identify SCR, and new urine and blood biomarkers that define the presence or absence of SCR.

Results: Serum creatinine is an unreliable index of SCR. Surveillance biopsies are the method most utilized to detect SCR. However, these have significant drawbacks. New biomarkers show promise. These biomarkers include blood gene expression profiles and donor derived-cell free DNA; urine gene expression profiles; urinary cytokines, chemokines, and metabolomics; and other promising blood and urine tests.

Conclusion: Specific emphasis is placed on studies carried out in pediatric kidney transplant recipients.

Trial registration: ClinicalTrials.gov: NCT03719339.

Background: Pulmonary vein stenosis (PVS) is a rare condition in which neointimal proliferation leads to venous and arterial hypertension. Little is known about PVS after heart transplant (HTx) in children. We sought to describe the characteristics and outcomes of children who develop PVS after HTx.

Methods: We performed a retrospective review of patients ≤18 years old who underwent HTx at two HTx centers between April 2012 and October 2023. Patients with PVS were identified via database queries. Cardiac diagnosis, PVS location and extent, and outcomes were recorded.

Results: Over 11.5 years, 422 patients underwent HTx across both centers. Nineteen patients with PVS (10 male) were identified, 15 with de novo PVS. Sixteen had underlying congenital heart disease (CHD), two with anomalous pulmonary venous return. PVS was diagnosed at a median of 2 months (range 2 weeks to 14 years) after HTx. At time of initial diagnosis, 13 patients had one-vessel PVS. At final follow-up, 7/19 (37%) had increases in the number of vessels involved. Six patients underwent surgery, and nine patients had stent or balloon angioplasty. Two patients were treated for pulmonary hypertension following PVS diagnosis. Three patients died from right heart failure secondary to PVS.

Conclusions: This is the largest study to describe the characteristics of post-HTx PVS in children. PVS occurs in 4.5% of HTx, and underlying CHD is a strong risk factor. Multiple vessels can be involved and may require catheter-based or surgical intervention. Clinicians must be vigilant in monitoring the development of PVS in this population.