Pediatric Solid Organ Transplant Recipients Research Articles

Adult and late adolescent complications of pediatric solid organ transplantation.

There have been over 51 000 pediatric solid organ transplants since 1988 in the United States alone, leading to a growing population of long-term survivors who face complications of childhood organ failure and long-term immunosuppression. This is an educational review of existing literature. Pediatric solid organ transplant recipients are at increased risk for risk for cardiovascular and kidney disease, skin cancers, and growth problems, though the severity of impact may vary by organ type. Pediatric recipients often are able to complete schooling, maintain a job, and form family and social networks in adulthood, though at somewhat lower rates than the general population, but face additional challenges related to neurocognitive deficits, mental health disorders, and discrimination. Transplant centers and research programs should expand their focus to include long-term well-being. Increased collaboration between pediatric and adult transplant specialists will be necessary to better understand and manage long-term complications.

Incidence, causative organisms, and risk factors of bloodstream infections in pediatric liver transplant patients: a systematic review.

Bacterial bloodstream infections (BSI) are the leading cause of mortality and morbidity in pediatric solid organ transplant recipients. This systematic review aimed to pool global data from leading transplant institutions and identify the overall incidence, risk factors, and causative organisms of BSI in pediatric liver transplant recipients. A systematic review of the PubMed and OVID databases was conducted from 2000 to 2022. The initial search yielded 252 unique articles, which were independently reviewed by 2 authors. Articles that reported pediatric-specific data on BSI in isolated liver transplant patients were included, including the incidence of BSI, isolated organisms, and involved risk factors involved. This systematic review was registered with PROSPERO (ID: CRD42023403206). Fourteen articles from the United States, France, Iran, Japan, Korea, South Africa, Thailand, and Turkey were included. A total of 4,812 liver transplants were included in the final analysis. The mean patient age was 25 months (age range, 0-18 years), and 50.9% were male. The overall incidence of BSI was 23.5% (range, 14.7%-55%). The most commonly reported organisms were Staphylococcus epidermidis, Enterococcus, Klebsiella spp., and Escherichia coli. Among the risk factors studied, postoperative biliary complications, a medical history of biliary atresia, and younger age were the risk factors most commonly associated with BSI. Bacterial BSI after pediatric liver transplantation occur at a high incidence, with a unique organism profile notable for a higher percentage of gram-negative organisms. Further studies are required to determine the most appropriate prophylactic and empirical antibiotic management strategies for this population.

COVID-19 vaccination induces distinct T-cell responses in pediatric solid organ transplant recipients and immunocompetent children

Immune responses to COVID-19 vaccination are attenuated in adult solid organ transplant recipients (SOTRs) and additional vaccine doses are recommended for this population. However, whether COVID-19 mRNA vaccine responses are limited in pediatric SOTRs (pSOTRs) compared to immunocompetent children is unknown. Due to SARS-CoV-2 evolution and mutations that evade neutralizing antibodies, T cells may provide important defense in SOTRs who mount poor humoral responses. Therefore, we assessed anti-SARS-CoV-2 IgG titers, surrogate neutralization, and spike (S)-specific T-cell responses to COVID-19 mRNA vaccines in pSOTRs and their healthy siblings (pHCs) before and after the bivalent vaccine dose. Despite immunosuppression, pSOTRs demonstrated humoral responses to both ancestral strain and Omicron subvariants following the primary ancestral strain monovalent mRNA COVID-19 series and multiple booster doses. These responses were not significantly different from those observed in pHCs and significantly higher six months after vaccination than responses in adult SOTRs two weeks post-vaccination. However, pSOTRs mounted limited S-specific CD8+ T-cell responses and qualitatively distinct CD4+ T-cell responses, primarily producing IL-2 and TNF with less IFN-γ production compared to pHCs. Bivalent vaccination enhanced humoral responses in some pSOTRs but did not shift the CD4+ T-cell responses toward increased IFN-γ production. Our findings indicate that S-specific CD4+ T cells in pSOTRs have distinct qualities with unknown protective capacity, yet vaccination produces cross-reactive antibodies not significantly different from responses in pHCs. Given altered T-cell responses, additional vaccine doses in pSOTRs to maintain high titer cross-reactive antibodies may be important in ensuring protection against SARS-CoV-2.

Presentation, anagement, and outcomes of norovirus in adult and pediatric solid organ and hematopoietic stem cell transplant recipients: A multicenter, retrospective study.

Norovirus (NoV) can cause chronic relapsing and remitting diarrhea in immunocompromised patients. Few multicenter studies have described the clinical course, outcomes, and complications of chronic NoV in transplant recipients. A multicenter retrospective study of adult and pediatric SOT and HSCT recipients diagnosed with NoV between November 1, 2017, and February 28, 2021. Data were obtained from electronic medical records (EMR) and entered into a central REDCap database. Descriptive statistics were calculated. A total of 280 NoV+ patients were identified across eight sites. The majority were adults (74.1%) and SOT recipients (91.4%). Initial diagnosis of NoV occurred a median of 36 months post-Tx (IQR [15.0, 90.0]). Most NoV cases had >3 diarrheal episodes daily (66.0%), nausea and vomiting (60.1%). Duration of diarrhea varied greatly (median = 10 days, mean = 85.9 days, range (1, 2100)). 71.3% were hospitalized. Adjustment of immunosuppression, including reduction and discontinuation of mToR inhibitor, CNI, and/or MMF, was the most common management intervention for NoV. Other therapies resulted only in temporary improvement. Four patients died within 30 days and three others died by 180 days postdiagnosis. Clinically significant renal dysfunction was observed in 12.5% by 30 days and 21.4% by 180 days post-NoV diagnosis. In HSCT and SOT patients, NoV frequently resulted in severe symptoms, prolonged diarrhea (30% persistent with diarrhea for >30 days), and clinically significant renal dysfunction (up to 21% of patients). Utilized therapies did not reliably result in the resolution of infection demonstrating the need for more effective treatment.

Evaluation of valganciclovir's neutropenia risk in pediatric solid organ transplant recipients utilizing two dosing regimens.

Valganciclovir is approved for cytomegalovirus prophylaxis in pediatrics using the Pescovitz algorithm. There are reports of valganciclovir overdoses in children with low body surface area and overestimated creatinine clearance utilizing this algorithm. This study compared the incidence of neutropenia and cytomegalovirus infection between the Pescovitz and weight-based dosing algorithms. A single-center retrospective chart review from January 2010 to September 2018 was performed on pediatric heart, liver, and kidney transplant recipients, who received valganciclovir. Data were collected from the initiation of valganciclovir prophylaxis to 30 days after discontinuation. The primary objective was the incidence of neutropenia in patients receiving valganciclovir dosed by the Pescovitz versus weight-based dosing algorithms. This study included 187 pediatric transplant recipients who received valganciclovir dosed via the Pescovitz (62 recipients) or weight-based dosing algorithms (125 recipients). The incidence of neutropenia was higher in the Pescovitz (69.4%) compared to the weight-based dosing group (53.6%; p = .04) including moderate and severe neutropenia. Cytomegalovirus viremia was not significantly different between the two groups and occurred in 4.8% of the Pescovitz group compared to 2.4% of the weight-based group (p = .4). The incidence of neutropenia was greater in recipients receiving valganciclovir dosed via the Pescovitz algorithm compared to the weight-based dosing. There were no significant differences in regard to cytomegalovirus viremia or disease between the two groups.

Nontuberculous Mycobacterial Infections in Pediatric Solid Organ Transplant and Hematopoietic Cell Transplant Recipients.

The diagnosis of nontuberculous mycobacterial infections is challenging in pediatric solid organ transplant and hematopoietic cell transplant recipients due to the absence of specific clinical manifestations, limitations of sampling, prolonged times for culture and identification, and difficulty discerning colonization from clinical disease. Treatment is dependent on the nontuberculous mycobacterial species, disease type, and pattern of drug resistance. Treatment of nontuberculous mycobacterial infections involves prolonged durations of therapy using multiple medications, which are limited by toxicities and drug-drug interactions.

Viral meningoencephalitis in pediatric solid organ or hematopoietic cell transplant recipients: a diagnostic and therapeutic approach.

Neurologic complications, both infectious and non-infectious, are frequent among hematopoietic cell transplant (HCT) and solid organ transplant (SOT) recipients. Up to 46% of HCT and 50% of SOT recipients experience a neurological complication, including cerebrovascular accidents, drug toxicities, as well as infections. Defects in innate, adaptive, and humoral immune function among transplant recipients predispose to opportunistic infections, including central nervous system (CNS) disease. CNS infections remain uncommon overall amongst HCT and SOT recipients, compromising approximately 1% of total cases among adult patients. Given the relatively lower number of pediatric transplant recipients, the incidence of CNS disease amongst in this population remains unknown. Although infections comprise a small percentage of the neurological complications that occur post-transplant, the associated morbidity and mortality in an immunosuppressed state makes it imperative to promptly evaluate and aggressively treat a pediatric transplant patient with suspicion for viral meningoencephalitis. This manuscript guides the reader through a broad infectious and non-infectious diagnostic differential in a transplant recipient presenting with altered mentation and fever and thereafter, elaborates on diagnostics and management of viral meningoencephalitis. Hypothetical SOT and HCT patient cases have also been constructed to illustrate the diagnostic and management process in select viral etiologies. Given the unique risk for various opportunistic viral infections resulting in CNS disease among transplant recipients, the manuscript will provide a contemporary review of the epidemiology, risk factors, diagnosis, and management of viral meningoencephalitis in these patients.

Chronic Epstein-Barr viral load carriage after pediatric organ transplantation.

Epstein-Barr virus (EBV) infection and EBV-associated post-transplant lymphoproliferative disorder (EBV/PTLD) is one of the most devastating complications occurring in pediatric solid organ transplant (SOT) recipients. Observations of SOT recipients undergoing serial EBV monitoring to inform reduction of immune suppression to prevent EBV-/PTLD has identified patients who maintain chronic high EBV load (CHL) in their blood. The CHL carrier state has been seen more commonly in pediatric compared to adult transplant recipients. Some but not all CHL may progress to EBV/PTLD. However, little is known regarding the biology of this CHL carrier state and the optimal clinical approach to CHL has not been established. This review summarizes the current knowledge and evidence of chronic high EBV load and introduces commonly adopted approaches from experts in this field.

Durable immunity to EBV after rituximab and third-party LMP-specific T cells: a Children’s Oncology Group study

AbstractPosttransplant lymphoproliferative disease (PTLD) in pediatric solid organ transplant (SOT) recipients is characterized by uncontrolled proliferation of Epstein-Barr virus–infected (EBV+) B cells due to decreased immune function. This study evaluated the feasibility, safety, clinical and immunobiological outcomes in pediatric SOT recipients with PTLD treated with rituximab and third-party latent membrane protein–specific T cells (LMP-TCs). Newly diagnosed (ND) patients without complete response to rituximab and all patients with relapsed/refractory (R/R) disease received LMP-TCs. Suitable LMP-TC products were available for all eligible subjects. Thirteen of 15 patients who received LMP-TCs were treated within the prescribed 14-day time frame. LMP-TC therapy was generally well tolerated. Notable adverse events included 3 episodes of rejection in cardiac transplant recipients during LMP-TC therapy attributed to subtherapeutic immunosuppression and 1 episode of grade 3 cytokine release syndrome. Clinical outcomes were associated with disease severity. Overall response rate (ORR) after LMP-TC cycle 1 was 70% (7/10) for the ND cohort and 20% (1/5) for the R/R cohort. For all cohorts combined, the best ORR for LMP-TC cycles 1 and 2 was 53% and the 2-year overall survival was 70.7%. vβT-cell receptor sequencing showed persistence of adoptively transferred third-party LMP-TCs for up to 8 months in the ND cohort. This study establishes the feasibility of administering novel T-cell therapies in a cooperative group clinical trial and demonstrates the potential for positive outcomes without chemotherapy for ND patients with PTLD. This trial was registered at www.clinicaltrials.gov as #NCT02900976 and at the Children's Oncology Group as ANHL1522.

Omicron Infections in Vaccinated Pediatric Solid Organ Transplant Recipients.

SARS-CoV-2 infection during the Omicron period was frequent amongst a cohort of vaccinated pediatric solid organ transplant recipients (pSOTRs) despite robust anti-receptor-binding domain (anti-RBD) antibody response, suggesting poor neutralizing capacity against Omicron subvariants. Breakthrough infections among pSOTRs were overall limited in severity.

458. Risk of COVID-19 and vaccine immunogenicity in pediatric solid organ transplant recipients – a single center study in South Korea

Abstract Background Solid organ transplant (SOT) recipients are at high risk for severe COVID-19 due to immunosuppressant (IS) use. Compared to adult SOT recipients (SOTRs), studies on risk and vaccination effectiveness in pediatric SOTRs are limited. We aim to investigate the epidemiologic characteristics of COVID-19 and vaccine immunogenicity in pediatric SOTRs. Methods This study was conducted at Severance Hospital in Korea, between 1999-2022. All SOTRs received SOT at the age ≤ 18 years were included. SOTRs who had a history of COVID-19 before SOT were excluded. Severe case was defined when there’s oxygen demand. Demographic data and information for risk factor exploration were retrospectively collected through chart review. Blood samples were collected prospectively after the COVID-19 vaccination policy for children was implemented. Humoral immunogenicity to WT, Delta and Omicron was investigated after 2 doses of BNT162b2 (BNT) using SARS-CoV-2 anti-S IgG titers, surrogate neutralization inhibition and plaque reduction neutralization tests. Post-vaccination samples of adult SOTRs were used as controls. Results A total of 118 SOTRs were included. The median age at SOT was 5 years (1-11 years), and the male to female ratio was 1:1.1. About 77% (91/118) had COVID-19 and 11% (10/91) of them were hospitalized for COVID-19 management. Four cases were severe cases and there was no death. The number of IS was significantly associated with the number of infection (p=0.04), distinct from hospitalization and severity (p=0.82 and 0.50), and there was no significant difference in outcomes between SOTRs received ≥ 3 doses of the COVID-19 vaccine and those received 0-2 doses (p=1.00, 0.21 and 1.00, respectively). Multiple logistic regression showed age at SOT and re-SOT as factors associated with number of COVID-19 (p=0.03, CI 0.36-0.96 and p=0.03, CI 1.74-6431.8). In vaccine immunogenicity analysis, humoral responses in pediatric SOTR were not lower than in adult SOTRs (table 1). However, the vaccine immunogenicity against Omicron was very poor compared to WT or Delta (figure 1). Conclusion Pediatric SOTR is susceptible to COVID, especially in older children at SOT and those who have undergone re-SOT. Two or Three doses of vaccination may be suboptimal for Omicron, so additional preventive measures are needed. Disclosures All Authors: No reported disclosures

Body Surface Area Valganciclovir Prophylactic Dosing is Associated with a Higher Rate of Drug-Associated Toxicities Compared to Body Weight Dosing in Pediatric Solid Organ Transplant Recipients

Abstract Background Valganciclovir (VGCV) is used for prevention of cytomegalovirus (CMV) in pediatric solid organ transplant (SOT) recipients who are at moderate or high risk for CMV infection or reactivation. Optimal dosing is not well defined, and both weight-based (WB) (15 mg/kg/dose) and body surface area-based (BSA) dosing (7 x BSA x creatinine clearance with an upper limit of 150 mL/min/1.73 m2) are used. We used a recently completed retrospective study on VGCV toxicity to compare the effects of these 2 dosing strategies on the proportion and the odds of CMV DNAemia, neutropenia, lymphopenia, and toxicity-related VGCV discontinuation or dose modification. Methods Data was collected from 6 US centers. Inclusion criteria were SOT recipients <20 years of age transplanted between January 2016 and December 2019, anticipated to receive VGCV prophylaxis with either dosing method for >/=3 months, and availability of >/=6 months of follow-up data post-transplant. Neutropenia and lymphopenia were defined as absolute neutrophil or lymphocyte count <1000 cells/microL. The number of patients who had premature discontinuation or dosing modification attributed to leukopenia or acute kidney injury (AKI) was quantified. Anticipated VGCV duration, dosing strategy, and threshold for making VGCV changes were at the discretion of each center for each patient. Cytopenias or toxicities that occurred within 15 days of SOT were excluded. Data were collected for one-year post-transplant and analyzed using Stata version 17.0. Groups were compared using Mann Whitney U test for continuous variables and chi-square test for categorical variables; logistic regression was used to calculate the odds ratio (OR) and 95% confidence interval (CI) with multivariable analysis. Results 412 patients met inclusion criteria. 312 patients were treated with WB and 100 with BSA dosing. Median age at transplantation was 5.1 (IQR 1.8-11.8) years and 42.7% were female. Transplanted organs included: liver 35.4%, kidney 33.5%, heart 22.3%, lung 6.6%, and other 2.2%. Within one year of transplantation, 23.4% and 12.2% of the WB group and 31.0% and 16% of the BSA group had at least one episode of CMV DNA detection in the plasma (DNAemia) and breakthrough CMV DNAemia while on VGCV prophylaxis, respectively (p=0.1 and p=0.3). There was no statistically significant difference in the odds of CMV DNAemia or breakthrough CMV DNAemia between dosing groups at one year when adjusted for: transplanted organ, CMV risk based on pre-transplant serostatus, duration of anticipated prophylaxis, age, receipt of CMV immunoglobulin, anti-thymocyte globulin, basiliximab, alemtuzumab, mycophenolate and corticosteroid (aOR=1.1, 95% CI: 0.6-1.8, p=0.8 and aOR=1.4, 95% CI: 0.6-2.9, p=0.4). However, the risk of all drug toxicity while on prophylaxis were significantly greater in BSA compared to WB group: neutropenia (50.0% vs 29.3%), lymphopenia (51.0% vs 15.0%), and toxicity-related VGCV discontinuation or modification (21% vs 6.7%) (each p<0.001). The BSA group had higher odds of neutropenia (aOR=2.3, 95% CI: 1.4-3.7, p=0.001), lymphopenia (aOR=7.0, 95% CI: 3.9-12.4, p<0.001), and toxicity-related VGCV discontinuation or modification (aOR=4.6, 95% CI: 2.2-9.3, p<0.001) while on prophylaxis when adjusted for age, organ, anticipated VGCV duration, and receipt of trimethoprim-sulfamethoxazole, anti-thymocyte globulin, basiliximab, alemtuzumab, mycophenolate and corticosteroid. Conclusions Results of this study indicate that BSA dosing of VGCV is associated with a significantly greater risk of toxicity without a decrease in CMV DNAemia.

RSV Infection and Preliminary Immunodeficiency Scoring Index (ISI) Results Among Pediatric Hematopoietic Cell Recipients (HCT) and Solid Organ Transplant Recipients (SOT): A Multi-Site U.S. Study

Abstract Background Respiratory syncytial virus (RSV) is among the most common causes of lower respiratory tract infections (LRTI) in children, with poorer outcomes more likely in immunocompromised hosts. The Immunodeficiency Scoring Index (ISI) to stratify the risk of severe disease has been developed and applied in adults undergoing transplantation with RSV infections. However, such scores are not available for children undergoing transplantation. Using a retrospective multi-site study, we developed an ISI score index for predicting RSV disease progression in pediatric transplant recipients. Methods Pediatric (< 18 years old at transplant) HCT and SOT recipients at 22 U.S. transplant centers who underwent transplant (2010-2019) and had RSV detected within 365 days of conditioning or transplant were included. De-identified data were entered by the participating sites in the REDCap database. The ISI score criteria are listed in Table 1. The cases were summarized using the ISI score. Progression to LRTI and death related to RSV were summarized using the ISI score. Fisher’s exact and non-parametric tests were used to compare ISI risk categories with the outcomes of interest (progression to LRTI and RSV-related mortality). Results In total, 352 patients were included in this analysis (220 HCT and 132 SOT). The majority were male (55%) and Caucasian/white (58.2%), with a median age of 4 years (range, 0 – 17 years). In total, 27 cases progressed to LRTI, and three deaths were related to RSV. The median ISI score was 1 (range: 0–10). The cases were categorized into low (245, 69.6%), moderate (81, 23%), or high (26, 7.4%) ISI risk categories (Table 1). The ISI score categories did not significantly predict progression to LRTI- or RSV-related deaths. Conclusion RSV is associated with poor outcomes in immunocompromised pediatric patients. Development of immunodeficiency scoring index criteria could prove helpful in categorizing the risk for pediatric patients. Additional work is needed to develop a scoring system that effectively predicts pediatric immunocompromised patients at the greatest risk of RSV-related morbidity and mortality. Further investigation of our data from this large multi-site study is needed to assess all potential risk factors and scoring criteria definitions.

Risk of COVID-19 infection in pediatric solid organ transplant recipients: a single center study in South Korea

Risk of COVID-19 infection in pediatric solid organ transplant recipients: a single center study in South Korea

Approach to vaccinating the pediatric solid organ transplant candidate and recipient.

Solid organ transplantation (SOT) candidates and recipients are at increased risk for morbidity and mortality from vaccine-preventable infections. Children are at particular risk given that they may not have completed their primary immunization series at time of transplant or have acquired natural immunity to pathogens from community exposures. Multiple society guidelines exist for vaccination of SOT candidate and recipients, although challenges remain given limited safety and efficacy data available for pediatric SOT recipients, particularly for live-vaccines. After transplant, individual patient nuances regarding exposure risks and net state of immunosuppression will impact timing of immunizations. The purpose of this review is to provide readers with a concise, practical, expert-opinion on the approach to vaccinating the SOT candidate and recipient and to supplement existing guidelines. In addition, pediatric-specific knowledge gaps in the field and future research priorities will be highlighted.

Bone health in children undergoing solid organ transplantation.

Pediatric solid organ transplant recipients are a unique and growing patient population who are at risk for metabolic bone disease both before and after transplantation. The odds of sustaining a fracture in adulthood are significantly higher if an individual has sustained at least one childhood fracture, therefore, close monitoring before and after transplant is essential. Emerging data in patients with chronic kidney disease mineral and bone disorder (CKD-MBD) and hepatic osteodystrophy highlights the role of fibroblast growth factor 23 in the pathogenesis of metabolic bone disease in these conditions. While dual X-ray absorptiometry (DXA) is the most widely used imaging modality for assessment of bone mass in children, quantitative computer tomography (QCT) is an emerging modality, especially for patients with glucocorticoid-induced osteoporosis. Solid organ transplantation improves organ function and quality of life; however, bone mineral density can decline following transplantation, particularly during the first three to six months. Immunosuppressive medications, including glucocorticoids, are a major contributing factor. Following transplant, treatment should be tailored to achieve mineral homeostasis, correct nutritional deficiencies, and improve physical conditioning. In summary, early identification and treatment of metabolic bone disease can improve the bone health status of pediatric transplant recipients as they enter adulthood. http://links.lww.com/MOP/A71.

Approach to suspected donor-derived infections.

Prevention of donor-derived disease among pediatric solid organ transplant recipients requires judicious risk-benefit assessment. Comprehensive guidelines outline specific donor risk factors and post-transplant monitoring strategies to prevent and mitigate transmission of HIV, hepatitis B, and hepatitis C. However, elimination of unanticipated donor-derived infections remains challenging. The objectives of this review are to (1) define risk of anticipated vs. unanticipated disease transmission events in pediatric solid organ transplant recipients; (2) discuss donor presentations that confer greater risk of unanticipated disease transmission; (3) develop a matrix for consideration of donor acceptance; and (4) discuss limitations and future directions for donor screening. Although solid organ transplant confers inherent risk of infection transmission, the risk of significant disease transmission events may be mitigated by a comprehensive approach including donor assessment, consideration of recipient need, post-transplant monitoring, and early intervention.

Population pharmacokinetic models of tacrolimus in paediatric solid organ transplant recipients: A systematic review.

This study aimed to provide up-to-date information on paediatric population pharmacokinetic models of tacrolimus and to identify factors influencing tacrolimus pharmacokinetic variability. Systematic searches in the Web of Science, PubMed, Scopus, Science Direct, Cochrane, EMBASE databases and reference lists of articles were conducted from inception to March 2023. All population pharmacokinetic studies of tacrolimus using nonlinear mixed-effect modelling in paediatric solid organ transplant patients were included. Of the 21 studies reviewed, 62% developed from liver transplant recipients and 33% from kidney transplant recipients. Most studies used a 1-compartment model to describe tacrolimus pharmacokinetics. Body weight was a significant predictor for tacrolimus volume of distribution (Vd/F). The estimated Vd/F for 1-compartment models ranged from 20 to 1890 L, whereas the peripheral volume of distribution (Vp/F) for 2-compartment models was between 290 and 1520 L. Body weight, days post-transplant, CYP3A5 genotype or haematocrit were frequently reported as significant predictors of tacrolimus clearance. The estimated apparent clearance values range between 0.12 and 2.18 L/h/kg, with inter-individual variability from 13.5 to 110.0%. Only 29% of the studies assessed the generalizability of the models with external validation. This review highlights the potential factors, modelling approaches and validation methods that impact tacrolimus pharmacokinetics in a paediatric population. The clinician could predict tacrolimus clearance based on body weight, CYP3A5 genotype, days post-transplant or haematocrit. Further research is required to determine the relationship between pharmacogenetics and tacrolimus pharmacodynamics in paediatric patients and confirm the applicability of nonlinear kinetics in this population.

Parent and healthcare provider views of live varicella vaccination of pediatric solid organ transplant recipients.

Live attenuated varicella vaccine (LAVV) has historically been contraindicated in children who are immunocompromised due to solid organ transplant (SOT) because of safety concerns. Recently, clinical guidelines were developed that support post-transplant varicella vaccination in selected SOT recipients based on emerging evidence of LAVV safety. This qualitative study sought to explore barriers and facilitators to implementing the new guidelines, as well as acceptability of LAVV among healthcare providers (HCPs) and parents. HCPs and parents of transplant recipients were recruited from four sites using purposive sampling. Data from semi-structured interviews were analyzed using an Interpretive Description approach that incorporated data from the interviews, academic knowledge and clinical experience, and drew from Grounded Theory and Thematic Analysis. The theoretical framework used was Adaptive Leadership. Thirty-four participants (16 HCPs and 18 parents) were included in the analysis. Parents developed skills in adaptive leadership that included strategies to protect their child against infectious diseases. Foundational information that live vaccines were absolutely contraindicated post-transplant "stuck" with parents and led them to develop strategies other than vaccination to keep their child safe. Some parents struggled to understand that information previously presented as a certainty (contraindication of LAVV) could change. Their approach to adaptive leadership informed their appraisal of the new vaccination guidelines and willingness to accept vaccination. HCPs should adopt a family-centered approach to communicating changing guidelines that considers parents' approach to adaptive leadership and discusses the changing nature of medical evidence. Trust between HCPs and parents can facilitate these conversations.

A quick algorithmic review on management of viral infectious diseases in pediatric solid organ transplant recipients.

Pediatric solid organ transplant is a life-saving procedure for children with end-stage organ failure. Viral infections are a common complication following pediatric solid organ transplantation (SOT), which can lead to increased morbidity and mortality. Pediatric solid organ transplant recipients are at an increased risk of viral infections due to their immunosuppressed state. The most commonly encountered viruses include cytomegalovirus (CMV), Epstein-Barr virus (EBV), herpes simplex virus (HSV), varicella-zoster virus (VZV), adenoviruses, and BK polyomavirus. Prevention strategies include vaccination prior to transplantation, post-transplant prophylaxis with antiviral agents, and preemptive therapy. Treatment options vary depending on the virus and may include antiviral therapy and sometimes immunosuppression modification. This review provides a Quick Algorithmic overview of prevention and treatment strategies for viral infectious diseases in pediatric solid organ transplant recipient.