Pediatric Transplantation最新文献

Background: The first 35 years of pediatric heart transplantation (pHTx) in Sweden were investigated to determine outcomes following listing and transplantation, investigate sub-populations of recipients, and describe the presence of donor-specific antibodies (DSA) in a contemporary cohort.

Methods: Swedish children < 18 years, listed from 1/1/1989 to 31/12/2023, were included. The cohort was split based on the era of transplantation (ERA I: 1989-2008, ERA II: 2009-2023).

Results: A total of 254 children were listed and 185 (72.8%) reached pHTx, with no loss to follow-up. Waiting list duration was 62 days and increased over time, while mortality on the waiting list decreased (30.5% in ERA I, 8.8% in ERA II). Congenital heart disease was the etiology of heart failure in 36.2% of recipients, including 24.9% with univentricular physiology. The frequency of ABO-incompatible transplantations was 9.3% and 8.0% were considered to be at high immunological risk pre-pHTx due to pre-formed HLA-antibodies with mean fluorescence intensity ≥ 5000. Ventricular assist device (VAD) was used in 26.9% of recipients. Long-term survival was not affected by age, heart failure etiology, the use of pre-transplant VAD, or elevated baseline indexed pulmonary vascular resistance. Era of transplantation was a determinant of listing, but not post-pHTx outcome. Survival at 1-, 10-, and 30-year follow-up was 94.5%, 79.4%, and 57.1%, respectively. Of the total de novo DSA burden, 45.9% were HLA-DQ-type specific. Re-transplantation was performed in 5.9% of recipients.

Conclusions: A high quality of care has been achieved in Sweden, despite modest pHTx numbers, in cooperation with the Scandiatransplant organization.

Background: Hemophagocytic lymphohistiocytosis (HLH) is a life-threatening syndrome characterized by the aberrant activation of macrophages. Liver dysfunction is often observed in patients with HLH and has the potential to advance to acute liver failure (ALF). However, limited data exist regarding the application of liver transplantation (LTx) for the management of HLH-associated acute liver failure (HLH-ALF).

Methods: A retrospective analysis was conducted on a pediatric case of LTx for HLH-ALF at our center, and previously documented cases of liver transplantation for this condition were summarized.

Results: A 4-year-old girl was admitted with intermittent fever that had persisted for more than 2 months. She exhibited recurrent high fever (40°C), accompanied by hepatosplenomegaly and superficial lymphadenopathy. The patient's condition rapidly progressed and fulfilled the HLH-2004 diagnostic criteria. The liver function progressively deteriorated. The patient was diagnosed with secondary HLH-ALF. Given the patient's critical condition, she underwent a living donor liver transplantation from her mother (left lobe). Despite experiencing rejection and human herpes virus 6 (HHV 6) infection, the patient recovered well and achieved stable disease.

Conclusion: This experience underscores the potential effectiveness of LTx in the management of HLH-ALF. Prompt investigation and intervention are crucial for patients with HLH exhibiting ALF. Although complex post-transplantation complications may arise, LTx remains a viable treatment option for HLH-ALF.

Background: Childhood overweight and obesity have been hypothesized to pose challenges in pediatric kidney transplantation due to potential complications and resultant worse outcomes. Herein, we aimed to determine if pediatric patients with an elevated body mass index (BMI) (> 85th percentile) are at higher risk for short-term complications following kidney transplantation.

Methods: Following a review of our transplant database (2010-2020), patients > 2-18 years were assigned to groups based on BMI percentiles at the time of surgery: normal (5th-85th percentile; n = 120) and obese/overweight (> 85th percentile; n = 60). Patients were matched using a 1-to-2-ratio nearest-neighbor propensity score matching adjusting for underlying diagnosis, sex, and age. The primary outcome was postoperative complications classified according to Clavien-Dindo, and secondary outcomes included postoperative creatinine and kidney graft rejection.

Results: One hundred eighty patients (n = 120 in the control and n = 60 in the overweight and obese group) were included. There was no significant difference in postoperative complications (72/120 vs. 40/60, p = 0.42). We noted no difference in nadir creatinine (7 days, [interquartile range (IQR) 1, 679] and 9 days, [IQR 1, 690], p = 0.11), postoperative creatinine levels at 3-, 6-, and 12-months post-transplantation, or rejection rates (8.4% and 8.4%, p > 0.99) between normal weighed and obese/overweight patients. However, more overweight and obese patients required intraoperative blood transfusions (55% and 33.4%, p = 0.006) and longer hospital stays (18.0 [IQR 9, 133] and 15.0 [IQR 7, 49], p = 0.02).

Conclusions: It appears as though overweight and obese pediatric kidney transplant patients do not experience more postoperative complications. We propose that overweight and obesity should not be considered criteria to exclude pediatric patients from undergoing kidney transplantations.

Background: Antibody-mediated rejection (AMR) remains a significant complication following heart transplantation, contributing to graft dysfunction and reduced survival. Donor-derived cell-free DNA (dd-cfDNA) is emerging as a non-invasive biomarker for detecting and monitoring graft injury, correlating with episodes of rejection and response to treatment. Daratumumab, an anti-CD38 monoclonal antibody targeting plasma cells, has shown promise in treating AMR. We present a case series of pediatric and young adult heart transplant recipients demonstrating donor-derived cell-free DNA's potential utility in monitoring for AMR and the effect of therapies including daratumumab.

Case descriptions: We report five cases showing that elevated dd-cfDNA correlated with pathological AMR (pAMR), and treatment with daratumumab improved both pAMR and dd-cfDNA levels. Most of our patients had persistently elevated donor-specific antibody (DSA) as observed by MFI values; however, there was a reduction in DSA titer that corresponded with improvement in pAMR and dd-cfDNA levels. Recurrent increases in dd-cfDNA were also useful in guiding the need for repeat treatment with daratumumab. Although DSA levels often remained elevated despite histologic improvement, decreasing dd-cfDNA levels correlated more closely with the resolution of AMR.

Conclusion: In this case series of pediatric and young adult heart transplant recipients, our findings suggest that dd-cfDNA can serve as a valuable biomarker for diagnosing AMR and treatment response, which are not often reflected by DSA MFI alone. Our dd-cfDNA data supports the efficacy of daratumumab in treating AMR and may guide the need for ongoing treatment. Further studies are warranted to validate these findings and establish guidance for the use of daratumumab and dd-cfDNA in this patient population.

Pediatric liver transplantation (PLT) is challenged by anatomical variability and small vessel size, especially in partial grafts. This review outlines strategies to minimize and manage complications of hepatic vein (HV) and portal vein (PV) reconstruction. HV reconstruction employs vein unification, direct caval implantation, or interposition grafts to prevent outflow obstruction, with diagnosis and management guided by imaging and interventional radiology. PV reconstruction in small recipients requires direct anastomosis, interposition grafts, or venoplasty, with intraoperative assessment of flow and pressure. PV thrombosis and stenosis are managed endovascularly or surgically, including Meso-Rex bypass. Individualized approaches and multidisciplinary care have improved outcomes in PLT.

Background: Liver transplantation remains the only treatment for end-stage liver disease and acute liver failure in children. In the pediatric population, the main challenge is the scarcity of deceased donors. To overcome this, partial liver grafts from living donors are utilized to expand the donor pool. This approach, however, is linked with a higher frequency of surgical and biliary complications, occurring in up to 45% of cases. The study aimed to assess the incidence and factors influencing biliary complications in children undergoing liver transplantation from living donors and the impact on long-term transplant success.

Methods: The study included 330 patients who underwent primary liver transplantation from living donors between 1999 and 2017 at the Department of Pediatric Surgery and Organ Transplantation of The Children's Memorial Health Institute. It identifies the types and frequency of biliary complications, risk factors, treatment methods, and impact on graft function and patient survival.

Results: Biliary complications were observed in 22.7% of the patients, including 14.2% of bile leaks and 9,7% of biliary obstructions. No significant risk factors for bile leaks were identified. Risk factors for a biliary stricture included primary liver tumors, multiple graft arteries, operation > 8 h, hepatic artery thrombosis, and acute rejection. Biliary complications did not significantly impact the long-term survival of grafts or recipients.

Conclusions: Biliary complications remain a significant concern in pediatric liver transplants from living donors. Managing these complications requires a tailored approach. Despite these complications, the overall long-term survival of grafts and patients remains unaffected.

Background: Hematopoietic cell transplantation (HCT) is the only curative treatment for chronic active Epstein-Barr virus infection (CAEBV). While HCT is needed at the appropriate time, there are sometimes difficulties in securing an appropriate donor, making HLA haploidentical donor an alternative option. Recently, post-transplant cyclophosphamide (PTCy) has rapidly gained popularity as a safe graft-versus-host disease (GVHD) prevention strategy for HCT from HLA haploidentical donors; however, there are only a few reports of its use for CAEBV.

Method: A retrospective chart review was completed for two pediatric CAEBV cases who underwent HLA haploidentical HCT (Haplo-HCT) with PTCy.

Result: A 6-year-old girl diagnosed with CAEBV previously underwent HCT twice from an HLA 8/8 matched brother, which both failed due to secondary graft failure. A third HCT was planned with a peripheral blood stem cell from her haploidentical father. She received a busulfan-based reduced intensity conditioning regimen. PTCy, mycophenolate mofetil, and tacrolimus were used for GVHD prophylaxis. Engraftment was achieved with full donor chimerism, and she remained in complete remission. A 7-year-old girl also diagnosed with CAEBV underwent HCT from her haploidentical mother with the same conditioning regimen and GVHD prophylaxis as the previous case. Engraftment was achieved with full donor chimerism. She suffered grade II (skin stage 3) acute GVHD and transplant-associated thrombotic microangiopathy, which were both treated successfully. She remained in complete remission.

Conclusions: Haplo-HCT with PTCy was safely performed for two pediatric CAEBV patients. Haplo-HCT may be a useful transplant option for CAEBV patients without a matched donor option.

Background: With advances in respiratory care allowing for improved survival, cardiomyopathy has emerged as the leading cause of death in patients with Duchenne Muscular Dystrophy (DMD). As end-stage heart failure emerges as the primary life-limiting complication in DMD patients, their consideration for advanced heart failure therapies, including ventricular assist devices (VADs) and/or heart transplantation (HT), is increasing. To date, however, there are few published reports of HT in DMD patients.

Methods: We report a case of HT in an 18-year-old young man with DMD, end-stage heart failure, respiratory insufficiency requiring nocturnal noninvasive ventilation, and retained ambulation with the use of a cane, who was declined for VAD and HT at an adult heart transplant center; he then received an LVAD, followed by HT after 362 days of support at a pediatric center.

Results: At 3.5 years of follow-up, the patient has excellent graft function and modestly improved pulmonary mechanics, though has experienced a functional decline from ambulatory status to the need for full assistance with activities of daily living.

Conclusions: This case underscores the importance of individual consideration for HT in patients with DMD, provides additional insight into the unique risks of VAD support in these patients, and further builds upon the existing experience that acceptable post-HT outcomes are achievable in this population.

Background: The Society of Pediatric Liver Transplantation (SPLIT) has undergone tremendous growth with > 45 sites contributing data focusing on improving outcomes in pediatric liver transplantation (LT). We report and compare outcomes from the SPLIT Registry.

Methods: Patients < 18 years with first-time LT only enrolled into the SPLIT Registry between 2011 and 2023 were included. Data was stratified into eras from the last published registry update (era 1: 2011-2018, era 2: 2018-2023).

Results: Three thousand five hundred four participants from 47 centers were included (era 1: n = 2159; era 2: n = 1345). Age distribution differed with more children < 1 year. of age at LT in era 2 (era 1: 29% vs. era 2: 33%, p = 0.01). Indications for LT were similar, with biliary atresia (38.8%) and metabolic disease (16.0%) being most common. Exception point use was higher in era 2 (era 1: 45% vs. era 2: 56%, p < 0.001). No difference in graft type (deceased: 81% era 1 vs. 78% era 2, p = 0.78), patient survival at 90 days (era 1: 98.7% vs. era 2: 98.3%), 1 year (era 1: 97.2 vs. era 2: 96.8%), or 3 years (era 1: 95.3% vs. era 2: 95.2%) was noted. Rate of hepatic artery thrombosis was lower in era 2 (era 1: 7% vs. era 2: 5%, p = 0.02).

Conclusions: Trends in pediatric LT within SPLIT note similar LT indications and graft type, higher utilization of exception points, and lower HAT rates despite transplanting more children < 10 kg. This data underscores the evolution of pediatric LT toward higher survivability and overall patient outcomes.