Pediatric Transplantation最新文献

Background: Solid Organ Transplant (SOT) provides a survival advantage for individuals with end organ failure. Little is known about the specific effects of immunosuppression on the competence of the immune system during the post-transplant period especially in the pediatric population, and current immunosuppression and prophylaxis practices are not well informed by immune data.

Methods: Blood samples from pediatric patients < 18 years old were collected prior to and 6- and 12 months after liver transplant. Peripheral blood mononuclear cells (PBMCs) were stimulated with PMA/Ionomycin and the phenotype and function of T cell subsets and NK cells were systematically characterized using cytometry by time-of-flight (CyTOF).

Results: In a cohort of 4 pediatric liver transplant patients, levels of CD4+ and CD8+ T cells, Tregs and NK cells at 6- and 12 months following liver transplant were similar to levels before transplant. Upon stimulation, pro-inflammatory, antiviral, and inhibitory T cell cytokines and enzymes were not reduced at 6 months post-transplant and remained stable at 12 months. IL-2 production, a tacrolimus target, from CD4+ and CD8+ T cells did not correlate with tacrolimus levels.

Conclusion: T cell function was not reduced by 6 months following liver transplant. This suggests that it might be safe to discontinue viral prophylaxis or initiate vaccinations sooner than previously suspected. Tregs functional marker expression was intact by 6 months post-transplant suggesting lower risk of rejection in this cohort. Tacrolimus level may not be a good indication for immunocompetence and T cell functional assays may be more predictive of susceptibility to infection.

Pediatric liver transplantation (LT) is a life-saving therapy, uniquely characterized by a favorable immunologic profile and a higher incidence of immune tolerance among long-term survivors. The liver's inherent tolerogenic environment, combined with the immunologic immaturity and thymic activity of children, may promote this phenomenon. Achieving operational tolerance (OT) minimizes lifelong immunosuppression (IS) toxicity, improving allograft longevity and quality of life. This review synthesizes current clinical and mechanistic evidence on immune tolerance in pediatric LT, evaluating the prevalence and outcomes of IS-withdrawal trials (e.g., WISP-R, iWITH, LIFT, OPTIMAL, SPLIT, ALLTOL). It also examines histopathologic correlations, clinical and immunologic predictors, and underlying molecular mechanisms and cell types such as regulatory T-cells, IL-10, TGF-β, CTLA-4 pathways, and so forth. It addresses the challenges and limitations in translating these advances into widespread clinical practice. OT is achievable in 15%-60% of carefully selected pediatric LT recipients in structured IS withdrawal protocols. Tolerant children maintain normal graft function, excellent survival, and preserved immunity without increased infection risk or the cumulative toxicities of chronic IS. Predictors of OT include younger age at transplant or withdrawal, non-immune disease etiology, longer post-transplant duration, and absence of donor-specific antibodies. Mechanistically, the liver's unique microenvironment, characterized by specific molecular pathways and cellular interactions, fosters immune regulation. Immune tolerance in pediatric LT is clinically attainable and significantly reduces the burden of lifelong IS. Progress in biomarker-guided and protocolized withdrawal has improved safety, yet standardization and broader implementation remain challenges. Continued mechanistic and translational research is essential to optimize patient selection, refine monitoring strategies, and safely extend IS minimization to all pediatric LT recipients.

Background: Optimal venous outflow is critical in living donor liver transplantation. In pediatric recipients, segment IV venous drainage is often overlooked but becomes essential in older children when adequate functional liver volume is required.

Case: We report a 5-year-old child weighing 15 kg with progressive familial intrahepatic cholestasis, who underwent living donor left lobe transplantation. The donor (mother) had a prominent segment IV tributary draining into the middle hepatic vein. To preserve optimal graft function, the segment IV venous tributary was reconstructed using the donor inferior mesenteric vein (IMV) as an interposition conduit. Postoperative Doppler confirmed satisfactory flow in the reconstructed vein. The child recovered uneventfully with good graft function on follow-up.

Conclusion: Donor IMV is a safe and versatile conduit for segment IV venous reconstruction in pediatric living donor liver transplantation, especially when segment IV drainage is essential for adequate functional graft volume.

Background: Up to 30% of patients develop anti-HLA antibodies following a single transfusion with leukoreduced packed red blood cells (pRBCs). While some speculate that irradiation of pRBCs could reduce the risk of allosensitization, its effect in clinical practice remains unclear.

Methods: A single-center, retrospective study was conducted with 93 pediatric solid organ transplant (SOT) candidates from January 2013 to July 2022. All participants had a baseline calculated panel reactive antibody (cPRA) of 0% and underwent repeat cPRA testing at least 28 days after pRBC transfusion to evaluate for de novo allosensitization. Patients were stratified by pRBC preparation: exclusively irradiated pRBC versus any exposure non-irradiated pRBC. The primary outcome was the incidence of interval allosensitization in each group.

Results: A total of 17 of 93 patients (18.3%) developed anti-HLA antibodies. In the non-irradiated group, allosensitization occurred in 8/39 patients (20.5%) compared to 9/54 (16.7%) in the irradiated group (χ² = 0.22, p = 0.7866). In multivariable analysis, the number of pRBC transfusions was the only risk factor to increase the odds of allosensitization (OR 1.18, p = 0.004). Number of non-pRBC sensitizing events was paradoxically found to be protective (OR 0.8, p = 0.03). Chronic immunosuppression did not mitigate allosensitization risk, although IVIG was associated with a non-significant risk reduction (OR 0.12, p = 0.07).

Conclusion: The number of pRBC transfusions remains the strongest modifiable risk factor for pre-transplant allosensitization in pediatric SOT candidates. Irradiation of pRBC did not significantly reduce the risk of transfusion-associated allosensitization in this population. IVIG may have a protective effect and should be further evaluated in a future, better powered study.

Cluster randomized controlled trials (CRTs) are valuable for interventions involving the clinical care team but often require larger sample sizes due to within-cluster correlation and between-cluster variability. The TAKE-IT-TOO pilot study aimed to estimate the intraclass correlation (ICC) necessary for designing a full-scale CRT to improve medication adherence in pediatric kidney transplant recipients. We examined different approaches to summarizing electronically measured adherence and assessed how these choices impact ICC estimation and sample size requirements. In TAKE-IT-TOO, seven centers were randomized to either an adherence-promoting intervention or a healthy-living intervention. Medication adherence was tracked using electronic pillboxes over a 4-week run-in period followed by a 10-week intervention. Variance estimates were calculated using generalized linear mixed models (GLMM) and used to derive ICC values. We compared two methods of summarizing adherence data and estimated the number of clusters and cluster sizes needed to detect an odds ratio of 1.5 between intervention groups across a range of plausible ICC values. The analysis demonstrated that using repeated adherence measures within each participant offered advantages over relying on a single summary measure, improving statistical power. However, large standard errors around variance estimates made precise ICC estimation difficult. Despite this, we identified a plausible range of ICC values and corresponding sample size requirements for future trials. The TAKE-IT-TOO study underscores the challenges of conducting CRTs in small populations and highlights the value of repeated outcome measures for maximizing statistical efficiency in adherence research.

Introduction: Cholestatic liver disease is the leading indication for pediatric liver transplantation (LT). Early detection and optimal care are often limited by socioeconomic barriers including racial disparities. This study examined racial disparities in demographics, waitlists, and post-transplant outcomes among pediatric LT recipients with cholestatic liver disease.

Methods: All pediatric patients (≤ 18 years) who were listed or received LT for cholestatic liver disease (Biliary Atresia, Caroli's, Choledochal cyst, PSC, PFIC, Alagille, and other non-specified cholestatic diseases) between 2010 and 2024 were retrospectively identified using the United Network for Organ Sharing (UNOS) database. The primary outcome of the study was waitlist mortality, graft failure, and post-transplant mortality stratified by race, specifically non-Hispanic whites (NHW), non-Hispanic blacks (NHBs), Hispanics, and others.

Results: 3501 pediatric patients underwent LT for cholestatic liver disease: 1663 (47.5%) were NHW, 795 (22.7%) were Hispanic, 648 (18.5%) were NHB, and 395 (11.3%) were of other races. NHW recipients were more likely to have private insurance (56.7% vs. 18.2%, p < 0.01) and experienced shorter waitlist times than Hispanic patients (175.9 vs. 189.4 days, p < 0.01). The 1-year survival rate was lower in NHB than in NHW recipients (94.8% vs. 96.8%, p = 0.04), with no significant difference at 5 years (93.7% vs. 95.4%, p = 0.13). Hispanic patients had similar 1-year (95.9%, p = 0.26) and 5-year (93.3%, p = 0.06) survival rates to NHW. NHB recipients had a significantly increased risk of mortality with a hazard ratio (HR) of 1.53 [95% CI: 1.05-2.22]. Predictive modeling using extreme gradient boosting showed a relative likelihood of increased mortality in NHB (3.91%) and Hispanic (3.14%) recipients.

Conclusion: Racial disparities significantly affect post-transplant outcomes in pediatric cholestatic liver disease. NHB and Hispanic children face a risk of higher mortality despite similar waitlist outcomes, highlighting the need for targeted interventions to promote equity in pediatric liver transplantation.

Background: Passenger lymphocyte syndrome (PLS) is a rare complication following solid organ transplantation (SOT) that has not been reported in pediatric lung transplantation. It consists of hemolysis by antibodies from donor B-lymphocytes against recipient red blood cells (RBCs).

Methods: We report the case of a 12-year-old girl who received bilateral lung transplantation for bronchiolitis obliterans secondary to graft-versus-host disease. She had undergone allogeneic matched unrelated hematopoietic stem cell transplantation (HSCT) 6 years prior for myelodysplastic syndrome (MDS). Details around the PLS event are reported, with emphasis on novel considerations.

Results: Lung transplant was uneventful with minor ABO mismatch between donor (O+) and recipient (A+), with a negative crossmatch. There was an abrupt drop in hemoglobin from 10.8 g/dL on post-operative day 11 to 6.6 g/dL on day 13. Direct antiglobulin test and markers for hemolysis were positive. Eluate test returned positive for anti-A1 antibody, confirming PLS. Transfusion with donor-type (O+) RBCs and IVIG were beneficial. A chimerism study revealed no recurrent MDS with fluorescence in situ hybridization revealing no circulating lung donor lymphocytes. The process was self-limiting and hemoglobin recovered.

Conclusions: This case is the first to highlight PLS following lung transplantation in a child, and informs around post-HSCT considerations. The novel use of chimerism studies and FISH can help elucidate the PLS course. It remains unclear if HSCT predisposes to PLS after subsequent SOT, although this may be due to sensitization to past RBC antigens.

Background: An ongoing quality improvement process was used to increase live and inactivated vaccination rates among vaccine-eligible pediatric liver transplant patients.

Methods: We evaluated 4-year outcomes (2019-2023) of Plan-Do-Study-Act (PDSA) cycles to guide vaccine counseling and management for pediatric liver transplant recipients. The annual posttransplant visit was used to provide families education regarding live and inactivated immunizations and obtain antibody titers for varicella, measles, mumps, rubella, Haemophilus influenzae type b, hepatitis A and hepatitis B. Vaccine recommendations were based on clinical criteria determined by our multidisciplinary team. Recommendations were then communicated with families and primary care providers (PCPs). Immunizations were administered by PCPs. Titers were obtained 4 weeks following immunization to assess response.

Results: Fifty-four patients met inclusion criteria. Recommendations for live (n = 38) and inactivated (n = 49) vaccines were given to patients. At the end of cycle 4, there was a notable increase in the number of patients who achieved protective titers to all live and inactivated vaccines in comparison to the start of cycle 1. The protective antibody titers to live vaccines declined in nearly half of our patients (n = 23/54, 43%), with the majority being to varicella vaccine and a smaller number to measles vaccine. However, most patients who were reimmunized (n = 13/14, 93%) had protective antibody titers following booster administration. There were no serious adverse effects to live vaccines.

Conclusions: We successfully recommended vaccinations and documented vaccine-induced immunity by implementing an active vaccine education and screening program. For PDSA cycle 5, we plan to continue our current practice and offer vaccines in transplant clinic, an identified barrier to vaccination.

Intestinal and multivisceral transplantation has evolved from an experimental to a life-saving procedure for children and adults with complications of gut failure (GF). Suboptimal long-term outcomes of transplant elicit recent advances in surgical and medical gut rehabilitation along with the introduction of glucagon-like peptide-2 (GLP-2) that has established a new paradigm achieving nutritional autonomy reserving transplantation for rescue. Notably, continued improvement of transplant has been observed over the last decade. The 2025 International Intestinal Transplant Registry (IITR) report demonstrates continued era-based improvement, with overall 5-year patient survival of 60% and graft survival of 51% for pediatric recipients, and 52% and 46%, respectively, for adult recipients. Over 90% of long-term transplant survivors achieve full nutritional autonomy. Contemporary cohorts show substantially better outcomes, reflecting advances in surgical technique and immunosuppression. Key developments include refined indications, sophisticated surgical techniques for complex anatomy, and updated immunosuppressive protocols. The integration of composite tissue transplantation, particularly abdominal wall allografts, vascularized and non-vascularized rectus sheath fascia has addressed closure challenges. Despite advances in transplantation, chronic rejection remains the primary barrier to long-term graft survival. Future directions include technological innovations in organ preservation, machine perfusion and organoid transplantation.

Background: In order to reduce the waiting time, new strategies have been developed to safely transplant donor and recipient pairs with mismatched blood groups. The present study examined the safety of the preparatory treatments and the midterm outcome of AB0 incompatible (AB0i) kidney transplantation in children.

Methods: We retrospectively analyzed 10 children who received a kidney transplant from an AB0i donor from 2012 to 2024 and 30 patients matched by sex, height, and weight who received an AB0 compatible (AB0c) living kidney transplant in the same period.

Results: In the AB0i group, preparatory treatment before KTx was well tolerated. The number of rejection episodes was comparable in the AB0i group and in the AB0c group (three episodes in three patients vs. seven episodes in six patients) during the observation period of 36 months, with rejections occurring earlier in the AB0c group. Infections were more frequent in the AB0c group than in the AB0i group (30 episodes in 23 patients [76%] vs. eight episodes in six patients [60%]). In the AB0i group, the 3-year graft survival rate was 90%; the 3-year patient survival was 100%. In the AB0c group, the 3-year graft survival was 86.8%, and the 3-year patient survival was 93.3%. There was no difference in graft survival (p = 0.08) and patient survival (p = 0.24) between the AB0i and AB0c groups.

Conclusions: AB0 incompatible kidney transplants can be safely performed in children with equivalent midterm graft and patient survival.