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Background: Short bowel syndrome (SBS) is a malabsorptive condition that develops as a result of massive resection of the small intestine and causes morbidities such as chronic diarrhea, dehydration attacks, parenteral nutrition (PN) dependence, and recurrent infections. Kidney transplantation in this patient group may be complicated by aforementioned morbidities, as well as the absorption problems of immunosuppressive drugs. Methods: We report the first pediatric patient (18‐month‐old male) with SBS secondary to volvulus who underwent a successful living related kidney transplantation with a primary diagnosis of autosomal recessive polycystic kidney disease and had a successful 4‐year follow‐up without intestinal transplantation. Results: Tacrolimus, mycophenolate mofetil (MMF), and prednisolone were administered for maintenance of immunosuppression after transplantation. The patient reached therapeutic trough levels of tacrolimus with usual doses. The 4‐year renal survival was excellent without a clinical evidence of rejection, despite long‐term necessity of PN and intravenous fluids. Conclusions: Kidney transplantation should not be avoided in patients with SBS solely because of concerns about the effectiveness of immunosuppressive therapy. Prednisolone, tacrolimus, and MMF combination was effective in our case, and these drugs can be considered as first‐line agents in these patients. [ABSTRACT FROM AUTHOR]

Background: Long‐term renal function and survival after kidney transplantation rely on appropriate immunosuppressive treatment to prevent the risk of rejection. New biomarkers are needed to accurately assess the degree of immunosuppression in renal transplant recipients in order to avoid organ rejection and the development of opportunistic infections. Highly prevalent in humans, torque teno virus (TTV), which belongs to the family Anelloviridae, is a small, nonenveloped, single‐stranded DNA virus which has not been linked with any specific human illness, but which constitutes a major component of the human virome. Host antiviral responses allow TTV levels to be controlled; however, viral persistence remains, explaining the high prevalence in human populations, including healthy individuals. Important confounders of TTV load include time since transplantation, age, gender, obesity, and smoking status. Aims: TTV‐based guidance of immunosuppressive drug dosing could help with risk stratification, reducing the risk of infection, graft rejection and oncologic disease on an individual level, enabling long‐term patient and graft survival. Methods: Original studies were accessed by a systematic search from electronic databases including PubMed, ScienceDirect and Wiley Online Library. Results: The presented data mainly derive from adult transplant recipients showing an association between TTV plasma levels and the immune status of the host: High‐TTV load and high immunosuppression are associated with a risk of infection, and low‐TTV load and low immunosuppression indicate a risk of rejection. However, there is minimal information on pediatric transplant recipients with further research required in this cohort. To date, it has been demonstrated that longer posttransplant times are significantly associated with lower TTV levels in children with renal transplant. Meanwhile, an association between lower TTV loads and increased risk of graft reject during the first year of transplantation was also reported. More recently, Eibensteiner et al. revealed a robust, independent association between TTV plasma load and the onset of Cytomegalovirus and BK virus infections. Conclusion: Data from randomized controlled trials are still missing, even in adults, but a multicenter randomized controlled trial for TTV‐guided immunosuppression in adult kidney recipients (TTVguideIT) began in 2022. There is, therefore, great promise for TTV levels to be used as a biomarker that could potentially improve both graft and patient survival in transplantation. [ABSTRACT FROM AUTHOR]

Background: Adolescent and young adult (AYA) solid organ transplant (SOT) recipients experience increased rates of rejection and graft loss surrounding the time of health care transition, in part due to poor medication adherence. This study aims to examine the impact of a once‐daily formulation of tacrolimus, LCP‐tacrolimus (LCPT), on medication adherence for AYA SOT patients. Methods: A retrospective descriptive analysis was performed for all patients who underwent SOT and were prescribed LCPT after the age of 12 at our single‐center pediatric hospital. Medication adherence was assessed via provider documentation and the medication level variability index (MLVI). Results: Twenty‐nine patients were prescribed LCPT as part of their immunosuppression regimen. Twenty patients were converted to LCPT from immediate‐acting (IR) tacrolimus; six patients were initiated immediately following transplant, and three patients were unable to receive LCPT due to insurance denial. There was a numeric improvement in medication adherence for converted patients when measured by provider assessment (45.0% vs. 68.4%, p =.140) and MLVI (40.0% vs. 71.4%, p =.276), though these did not reach statistical significance. There were no differences in episodes of rejection or adverse effects. LCPT prescription was not associated with decreased medication burden, and two patients transitioned back to IR tacrolimus due to increased cost. Conclusions: LCPT use did not significantly improve patient adherence; however, it resulted in numerically higher perceived and measured adherence rates. LCPT appears to be safe and effective in the management of SOT recipients; however, it may not affect pill burden and may result in a higher financial burden. Use may be considered for a select group of AYA SOT recipients. [ABSTRACT FROM AUTHOR]

Background: Healthcare providers who care for adolescent and young adult transplant recipients should be aware of contraception counseling and potential for pregnancy in this at‐risk cohort. Methods: This paper will review contraceptive options in general for transplant recipients. There will also be a review of common immunosuppressive medications and their risk profile regarding pregnancy after transplantation. Data from the Transplant Pregnancy Registry International were analyzed looking at recipients conceiving under the age of 21 and were compared to overall pregnancy outcomes. Results: Overall pregnancy outcomes in recipients under the age of 21 are like the adult cohort. Conclusion: It is imperative to provide contraception counseling to the adolescent and young adult and inform their caregiver that pregnancy can happen if the recipient is sexually active. Pregnant adolescent and young adult transplant recipients should be followed by a multidisciplinary team to assure a positive outcome for the recipient, transplant, and neonate. [ABSTRACT FROM AUTHOR]

BACKGROUND: Malnutrition, including obesity and undernutrition, among children is increasing in prevalence and is common among children on renal replacement therapy. The effect of malnutrition on the pre-transplant immune system and how the pediatric immune system responds to the insult of both immunosuppression and allotransplantation is unknown. We examined the relationship of nutritional status with post-transplant outcomes and characterized the peripheral immune cell phenotypes of children from the Immune Development of Pediatric Transplant (IMPACT) study. METHODS: Ninety-eight patients from the IMPACT study were classified as having obesity, undernutrition, or normal nutrition-based pre-transplant measurements. Incidence of infectious and alloimmune outcomes at 1-year post-transplantation was compared between nutritional groups using Grays test and Fine-Gray subdistribution hazards model. Event-free survival was estimated by Kaplan-Meier method and compared between groups. Differences in immune cell subsets between nutritional groups over time were determined using generalized estimating equations accounting for the correlation between repeated measurements. RESULTS: We did not observe that nutritional status was associated with infectious or alloimmune events or event-free survival post-transplant. We demonstrated that children with obesity had distinct T-and B-cell signatures relative to those with undernutrition and normal nutrition, even when controlling for immunosuppression. Children with obesity had a lower frequency of CD8 Tnaive cells 9-month post-transplant (p

Heart transplantation has become the standard of care for pediatric patients with end‐stage heart disease throughout the world. Since the first transplant was performed in 1967, the number of transplants has grown dramatically with 13 449 pediatric heart transplants being reported to The International Society of Heart and Lung Transplant (ISHLT) between January 1992 and June 30, 2018. Outcomes have consistently improved over the last few decades, specifically short‐term outcomes. Most recent survival data demonstrate that recipients who survive to 1‐year post‐transplant have excellent long‐term survival with more than 60% of those who were transplanted as infants being alive 25 years later. Nonetheless, the rates of graft loss beyond the first year have remained relatively constant over time; driven primarily by our poor understanding and lack of treatments for chronic allograft vasculopathy (CAV). Acute rejection, CAV, graft failure, and infection continue to be the major causes of death within the first 5 years post‐transplant. In addition, renal dysfunction, malignancy, and the need for re‐transplantation remain as significant issues that require close follow‐up. Looking forward, key challenges include improving donor utilization rates (including donation after cardiac death (DCD) and the use of ex vivo perfusion devices), the development of non‐invasive biomarkers for rejection, efforts to mitigate the long‐term effects of immunosuppression, and prevention of CAV. It is not possible to cover the entire evolution of pediatric heart transplantation over the last five decades, but in this review, we hope to touch on key observations, lessons learned, and practice changes that have advanced the field, as well as glance ahead to the next decade. [ABSTRACT FROM AUTHOR]

Background: Mycophenolate Mofetil (MMF) is an effective immunosuppressant used in kidney transplant recipients to prevent acute rejection. Complications such as diarrhea, leukopenia, and infections may necessitate the reduction or discontinuation of MMF. The objective of the study was to investigate the prevalence, timing, and reasons for MMF discontinuation and its association with outcomes in pediatric kidney transplant recipients. Methods: Seven Pediatric Nephrology Research Consortium (PNRC) centers participated in a retrospective analysis of kidney transplant recipients <21 years of age. Characteristics and outcomes of patients in whom MMF was discontinued were compared to those who continued taking MMF throughout the first 2 years post‐transplant. Results: The study population included 288 participants (mean age 11.2 years) from 7 North American transplant centers. MMF was discontinued in 93/288 (32%) of participants. Common reasons for discontinuation included infections (35%), diarrhea (32%), leukopenia (15%), and others (18%). Increased cumulative alloimmunity (55% vs. 42%, p =.02), increased number of hospitalizations (82% vs. 67%, p =.01), and viral replications (79% vs. 47%, p <.0001) were observed in the MMF discontinuation group compared to the continuation group. Greater eGFR decline also occurred in the MMF discontinuation group over 2 years of follow‐up (−7 vs. −1 mL/min/1.73 m2, p =.05). Conclusions: Almost a third of pediatric kidney transplant recipients who begin MMF for maintenance immunosuppression have it discontinued within the first 2 years post‐transplant, and this subset of patients is more likely to experience adverse outcomes. New strategies are needed to manage MMF therapy and improve post‐transplant outcomes. [ABSTRACT FROM AUTHOR]

Background: Chronic kidney disease (CKD) is a relatively rare childhood disease that is associated with a wide array of medical comorbidities. Roughly half of all pediatric patients acquire CKD due to congenital anomalies of the kidneys and urinary tract, and of those with congenital disease, 50% will progress to end‐stage kidney disease (ESKD) necessitating a kidney transplantation. The medical sequelae of advanced CKD/ESKD improve dramatically following successful kidney transplantation; however, the impact of kidney transplantation on neurocognition in children is less clear. It is generally thought that cognition improves following kidney transplantation; however, our knowledge on this topic is limited by the sparsity of high‐quality data in the context of the relative rarity of pediatric CKD/ESKD. Method: We conducted a narrative review to gauge the scope of the literature, using the PubMed database and the following keywords: cognition, kidney, brain, pediatric, neurocognition, intelligence, executive function, transplant, immunosuppression, and neuroimaging. Results: There are few published longitudinal studies, and existing work often includes wide heterogeneity in age at transplant, variable dialysis exposure/duration prior to transplant, and unaccounted cofounders which persist following transplantation, including socio‐economic status. Furthermore, the impact of long‐term maintenance immunosuppression on the brain and cognitive function of pediatric kidney transplant (KT) recipients remains unknown. Conclusion: In this educational review, we highlight what is known on the topic of neurocognition and neuroimaging in the pediatric KT population. [ABSTRACT FROM AUTHOR]

The overarching goal in the care of pediatric liver transplant recipients is to optimize allograft and patient health. Balancing immunosuppression to maintain allograft health while avoiding medication side effects is essential for long‐term survival and optimal quality of life in pediatric liver transplant recipients. Utilizing precision medicine to personalize immunosuppression, which includes minimization and withdrawal, is core to this effort. The unique anatomy and physiology of the liver make it more tolerant to immune‐mediated injury and a more favorable organ for immunosuppression minimization and withdrawal. However, several challenges exist. Standard biochemical values and histologic features may not reliably predict allograft health after a reduction in immunosuppression. Additionally, biochemical values alone do not reliably identify which patients can successfully develop operational tolerance, as there may be occult allograft injury despite normal liver enzymes. Finally, the durability of tolerance after successful reduction in immunosuppression remains uncertain over time. Innovative tools show promise in circumventing these challenges, but more research is needed to determine actual clinical utility. While immunosuppression‐free transplant may not be a current reality for most pediatric liver transplant recipients, strategies to safely minimize immunosuppression without compromising allograft health are within reach. Each liver allograft and recipient pair requires a different degree of immune modulation, and through a structured process of minimization and withdrawal, immunosuppression can indeed be tailored in a precise, personalized way to optimize outcomes. This review focuses on the progress that has been made to individualize immunosuppression in pediatric liver transplantation to ensure optimal allograft and recipient health. [ABSTRACT FROM AUTHOR]

The 12th Congress of the (IPTA) event in Austin, Texas, had over 400 attendees from 40 countries. The attendees included a diverse mix of pediatric transplant professionals from several specialties including physicians, surgeons, scientists, nurses, organ procurement personnel, advance transplant providers, pharmacists, administrators, fellows, residents, and students. The 4‐day event featured nearly 200 abstracts, 90 oral presentations, 24 mini oral presentations, and more than 80 poster presentations. All of these presentations encouraged vibrant discussions and supported the exchange of new clinical and basic science information regarding clinical care management, basic science research, socioeconomic, and ethical and organ donation issues relevant to pediatric transplantation. We briefly describe here the highest scored presented abstracts at IPTA 2023 that are divided into two categories: clinical and basic sciences. [ABSTRACT FROM AUTHOR]

Background: There is considerable variation in vaccination practices between pediatric transplant centers. This study aims to evaluate active immunization attitudes and practices among ERN‐TransplantChild centers and identify potential areas of improvement that could be addressed by shared evidence‐based protocols. Methods: A cross‐sectional questionnaire of attitudes and practices toward immunization of pediatric SOT and HSCT candidates and recipients was sent to a representative member of multidisciplinary teams from 27 European centers belonging to the ERN‐TransplantChild. Results: A total of 28/62 SOT programs and 6/12 HSCT programs across 21 European centers participated. A quarter of centers did not have an on‐site protocol for the immunizations. At the time of transplantation, pediatric candidates were fully immunized (80%–100%) in 57% and 33% of the SOT and HSCT programs. Variations in the time between vaccine administration and admission to the waiting list were reported between the centers, with 2 weeks for inactivated vaccines and variable time (2–4 weeks) for live‐attenuated vaccines (LAVs). Almost all sites recommended immunization in the post‐transplant period, with a time window of 4–8 months for the inactivated vaccines and 16–24 months for MMR and Varicella vaccines. Only five sites administer LAVs after transplantation, with seroconversion evaluated in 80% of cases. Conclusions: The immunization coverage of European pediatric transplant recipients is still inconsistent and far from adequate. This survey is a starting point for developing shared evidence‐based immunization protocols for safe vaccination among pediatric transplant centers and generating new research studies. [ABSTRACT FROM AUTHOR]

Background: This case report highlights a successful steroid‐free, low‐dose immunosuppressive protocol for renal transplantation in a pediatric patient with Schimke immuno‐osseous dysplasia with excellent 7‐year patient and graft survival. Schimke immuno‐osseous dysplasia is a rare multisystem disorder involving the kidney. Renal transplantation is a therapeutic option, but posttransplant mortality is high due to severe infections and posttransplant lymphoproliferative disease. Methods: A 10‐year‐old girl diagnosed with Schimke immuno‐osseous dysplasia and end‐stage renal disease underwent an AB0‐compatible living‐related kidney transplantation, with no donor‐specific antibodies. Our standard immunosuppression protocol was modified due to the risk of infection. Basiliximab was used as induction therapy, and a reduced dose of mycophenolate mofetil and tacrolimus was initiated following transplantation, maintaining the patient on a low tacrolimus target (3–5 μg/L). Mycophenolate mofetil was discontinued after 8 weeks due to neutropenia and the patient was kept on tacrolimus as monotherapy. Five years posttransplant the patient developed acute onset of neurological symptoms, consisting of ataxia, lack of voluntary coordination, balance, aphasia and dysphagia, and diplopia. She recovered without neurological deficits within 6 weeks. Extensive evaluation revealed no pathology. To avoid a possible a component of tacrolimus‐induced cerebral vasoconstriction, the immunosuppressive therapy was changed to everolimus. Results: Seven years posttransplant, the patient has experienced no serious infections, no rejections, and had excellent graft function, and no de novo donor‐specific antibodies. Conclusions: The present results indicate that low‐dose immunosuppressive therapy after renal transplantation with low immunological risk should be considered for patients with Schimke immuno‐osseous dysplasia. [ABSTRACT FROM AUTHOR]

Background: Chronic kidney disease (CKD) impacts long‐term morbidity in pediatric liver transplant (LT) recipients. The prevalence of estimated glomerular filtration rate (eGFR) < 90 mL/min/1.73 m2 (eGFR < 90) at our institution was 25% at 1 year post‐LT; thus, quality improvement (QI) project was initiated, aiming to decrease the prevalence of eGFR < 90 by at least 20% at 1 year‐post LT. Methods: Children post‐LT under 19 years from 2010 to 2018 were included. Three QI interventions were implemented starting 1/2016: documentation of blood pressure percentile (BP%) and eGFR, documentation of a kidney management plan if either was abnormal, and amlodipine initiation prior to hospital discharge after LT. We compared the prevalence of eGFR < 90 at 3, 12, and 24 months after LT in the pre‐ and post‐intervention period. Results: 68 patients in pre‐ and 42 in post‐intervention periods met inclusion criteria. Pre‐intervention BP%, eGFR, and kidney management plan were documented at 25%, 10%, and 22%, compared to 71%, 83%, and 71% post‐intervention, respectively. 22% of patients were started on amlodipine prior to discharge from LT in the pre‐ versus 74% in the post‐intervention period. Prevalence of eGFR < 90 at 3 m post‐LT was 19% in pre‐ versus 14% in the post‐intervention period (p =.31); at 12 months 24% versus 7% (p =.01) and at 24 months 16% versus 6% (p =.13), respectively. Significant non‐modifiable risk factors for eGFR < 90 were malignancy (RR = 4.5, p <.0001), metabolic disorder (RR = 2.6, p =.02), and age at transplant (7% increased risk per year of age, p =.007). Conclusion: By improving documentation of BP%, eGFR, and kidney management plan, the prevalence of eGFR < 90 was decreased by a relative 74% and 60% at 12 and 24 months post‐LT, respectively. [ABSTRACT FROM AUTHOR]

Background: Tacrolimus (TAC)‐mediated renal disease occurs in up to 70% of pediatric liver transplant (LT) recipients. The safety and efficacy of renal‐sparing immunosuppression using anti‐thymocyte globulin (ATG) induction and delayed TAC administration has not been studied in children. We evaluated the safety and efficacy of ATG induction on preserving renal function in children within the first year (Y1) post‐LT in a single‐center retrospective cohort study. Methods: Children under age 18 years of who received isolated LT from 2008 to 2020 with a GFR < 70 received renal‐sparing (RS) protocol consisting of ATG with methylprednisolone (MP), delayed TAC administration, lower initial TAC trough goals, and mycophenolate mofetil (MMF). The RS group was matched 1:2 by age and LT indication with standard immunosuppression (SI) group. Changes in renal function as well as adverse events within Y1 post‐LT were compared. Results: Forty‐four pediatric patients were included in the analysis, of which 13 received RS. As expected, the RS group had significantly lower mean TAC trough levels at 30 days (10.3 vs. 13.2, p =.001) post‐LT. Renal function was significantly preserved at 6 (−0.26 vs. 0.21, p =.004) and 12 months (−0.33 vs. 0.11, p =.003) post‐LT in the RS versus SI group as measured by mean change in serum creatinine, with similar trends observed in eGFR and cystatin C. ACR, sepsis, viremia, graft loss and mortality occurred at similar rates in both RS and SI groups. Conclusion: Induction immunosuppression with ATG and delayed TAC administration in children with renal impairment is safe and effectively preserves renal function during Y1 post‐LT. [ABSTRACT FROM AUTHOR]

Background: Late airway complications, as consequence of immunosuppression following pediatric liver transplantation are uncommonly reported. Methods: In this retrospective case series, we describe two young children presenting with symptoms of airway obstruction, secondary to differing pathologies in the supraglottic airway, as a result of immunosuppression following liver transplantation. Results: Case 1, a 2‐year‐old girl who presented with stridor 12‐months following liver transplantation, was found to have a proliferative soft tissue mass involving the supraglottic larynx. Biopsies were consistent with infiltrative eosinophilic laryngitis and associated eosinophilic esophagitis. Case 2, a 12‐month‐old female who presented with stridor 5‐months following liver transplantation, was found to have an exophytic soft tissue mass involving the supraglottis and hypopharynx. Biopsies revealed polymorphic Epstein–Barr virus (EBV) driven post‐transplant lymphoproliferative disease (PTLD). Case 1 was managed with local resection and high dose oral corticosteroids. Case 2 responded to debulking of the necrotic supraglottic mass, reduction of immunosuppression and rituximab. Conclusion: A high index of suspicion needs to be maintained for complications of immunosuppression for appropriate diagnosis of airway presentations following pediatric liver transplantation. Further research is necessary to improve early detection and consolidate management strategies for these airway lesions. [ABSTRACT FROM AUTHOR]

Background: Pediatric heart transplant recipients are at risk for complications from prolonged exposure to immunosuppressive drugs, pharmacokinetic challenges in maintaining consistent immunosuppression, and medication non‐adherence. Basiliximab (BAS), an interleukin‐2 receptor antagonist, is used for induction therapy across many pediatric heart transplant centers, but use as maintenance immunosuppression has not been well described. Methods: This was a retrospective, single pediatric center cohort study of heart transplant recipients who received BAS for maintenance immunosuppression (defined as >2 monthly doses) from January 1, 2011, to December 31, 2021. Results: Ten patients met study criteria with a median age of 17.5 (5–22) years and median 9.6 (1.2–18.9) years since transplant at time of BAS initiation. The primary indications for BAS use were recurrent rejection (n = 4), fluctuating immunosuppression levels (n = 3), and renal dysfunction (n = 3). A median of 5.5 (3–32) monthly BAS doses were received. Three patients had a rejection event while on BAS. Calcineurin inhibitor exposure was reduced in 70% of patients. Three of the 10 patients were alive at last follow‐up. There was one documented infection during BAS use, and no hypersensitivity reactions. Conclusions: Monthly BAS infusions were well tolerated and allowed for reduced calcineurin inhibitor exposure in most patients. Mortality commonly occurred despite BAS use, potentially reflecting the acuity of this patient cohort. BAS can be considered for maintenance immunosuppression in pediatric patients with fluctuating immunosuppressive levels and/or renal dysfunction. More studies are needed to determine long‐term outcomes and explore expanded use of BAS in the pediatric heart transplant population. [ABSTRACT FROM AUTHOR]

Background: Insulin hypersensitivity reactions are rare but serious and significantly affect the treatment of diabetes in children. Methods: A 13‐year‐old girl with type 1 diabetes, hypoglycemic unawareness, and treatment refractory allergy to available insulin preparations underwent a solitary pancreas transplant. Before the pancreas transplantation, she was receiving a continuous subcutaneous infusion of rapid‐acting insulin with an increasing need for antihistamines and steroids, negatively impacting her cognitive and social development. Her diabetes was poorly controlled, and her quality of life was progressively worsening. Results: Following the transplant, she recovered well from surgery and achieved euglycemia without needing exogenous insulin. She had two biopsy proven episodes of acute cellular rejection, successfully treated. Her cognitive development also accelerated. Notable improvement was noted both in her personal quality of life and her family's overall well‐being. Conclusions: This is the youngest pancreas transplant recipient with over 1‐year graft survival reported in the literature. Pancreas transplant alone in a teenager without indications for kidney transplantation could be considered a last resort treatment for diabetes when continuing insulin therapy presents a high level of morbidity. A pancreas transplant is a feasible treatment modality for patients with refractory insulin allergy. [ABSTRACT FROM AUTHOR]

Background: The COVID‐19 pandemic poses an increased risk of infection, severe illness, hospitalization and mortality for young people who are immunosuppressed, including lung transplant (LTx) recipients. The aim of this study was to explore the intersection between immunosuppression and COVID‐19, through the impacts of the pandemic upon the daily lives of young LTx recipients residing in the Australian state of Victoria. Methods: An exploratory qualitative research study was undertaken via consumer engagement. A purposive sample of 11 LTx recipients, residing in Victoria, was recruited during the first year of the COVID‐19 pandemic. Semi‐structured interviews were conducted to gain insights into their daily life and healthcare experiences, including the impacts of the COVID‐19 pandemic. Data were interpreted using thematic analysis. Results: Four major themes were identified: (1) occupational deprivation due to the intersection of COVID‐19 and lung transplant; (2) resilience and acceptance of restrictions; (3) infection control and vigilance about risk; and (4) care experiences of telehealth. Conclusions: Occupational deprivation emerged as a common theme, specifically in the context of loss of access to meaningful everyday activities of developmental significance. However, participants also commonly reflected upon their ability to flexibly adjust to changing socially regulated community and healthcare environments. A high degree of acceptance and compliance with public health orders was self‐reported, may be indicative of this cohort's long‐term experience of chronic illness and their understanding of the importance of minimizing infection risks. Youth‐informed healthcare strategies were identified as keystone to engaging them in institutional change and program adaptation during a pandemic. [ABSTRACT FROM AUTHOR]

Background: Atopic disorders are more common in children after heart transplant (HTx). We hypothesized that HTx at an early age and thymus excision (TE) affect development of T and B cells, especially regulatory T cells (Tregs), which help maintain tolerance. Methods: In this single‐center study including 24 patients transplanted between 2013 and 2018, we investigated lymphocyte patterns in relation to these factors using flow cytometry. Clinical data were collected from standardized questionnaires and medical charts. Patients were stratified into TE and non‐TE groups as well as patients with and without post‐transplant atopy development/worsening. Results: 64% of TE patients experienced new or worsening asthma/eczema post‐transplant compared to 20% of non‐TE patients. TE patients had higher total Treg proportions (CD4+CD25+CD127lo) than non‐TE patients (p =.043), but borderline significantly lower naïve Tregs (CD45RA+CD27−) (p =.057). Memory CD4+ T cells were higher in TE patients in trend (p =.084). Total Tregs did not differ between atopic/nonatopic groups, although naïve Tregs were significantly lower in atopic patients (p =.028). Memory CD4+ T cells were higher in atopic patients in trend (p =.082). IgM+IgD+ B cells were higher in nonatopic patients in trend (p =.064). Conclusions: New/worsening atopy is more common in thymectomized HTx children and is associated with alterations in T‐cell profiles. Avoiding TE may prevent these alterations and reduce incidence of atopy post‐HTx. [ABSTRACT FROM AUTHOR]

Background: BKV and BKVN are common in pediatric kidney transplant, but there is limited data on treatment approaches. Our objective was to study the prevalence of BKV and BKVN utilizing only plasma qPCR and report treatment outcomes with stepwise IR and IVIG. Methods: A retrospective study of all pediatric kidney transplants from 2013 to 2020. Excluded patients >21 years at transplant and immediate graft failure. Surveillance was conducted using only plasma BK qPCR at 1, 3, 6, 9, 12, 18, and 24 months and annually. BKV defined as ≥250 copies/ml and resolution as <250 copies/ml. Presumed BKVN as >10 000 copies/ml despite IR; and BKVN if confirmed on histology. Results: Fifty‐six patients were included in the study; 20 (35.7%) had BKV. BKV was associated with longer duration of stent, 40 vs. 33.5 days (p =.004). Two patients (3.5%) had confirmed, and 2(3.5%) had presumed BKVN. The first‐line treatment was IR in 100% of patients. BKVN confirmed and presumed received IVIG every month for six doses. Viral resolution was achieved in 70%, and no difference was noted in estimated glomerular filtration rate between BKV and non‐BKV group (p =.438). There were no rejection episodes, and graft survival was 100% over median follow‐up of 3 years. Conclusions: Plasma qPCR alone is adequate for screening and monitoring treatment of BKV and BKVN. A stepwise IR and IVIG resulted in BKV resolution in the majority of patients. Larger studies are required to study the role of IVIG in the treatment of BKVN. [ABSTRACT FROM AUTHOR]

Background: PTLD is a clinical condition with high mortality. Monitoring EBV replication can be a useful tool to avoid the development of PTLD. Materials and Methods: This was a retrospective analysis of 428 pediatric patients who underwent liver transplantation between 1989 and 2016. The patients were divided into 2 groups (transplanted before 2006, when PCR‐EBV was not monitored, and after 2006, when PCR‐EBV monitoring was started). Patients with continuous PCR measurements for EBV were evaluated for the impact of a reduction in immunosuppression or a change in immunosuppressants on the number of viral copies. A logistic regression model was applied to evaluate factors related to PTLD. Results: The prevalence of PTLD was 4.2%. After monitoring patients with PCR for EBV levels, a predominance of the most severe, monomorphic form of lymphoproliferative disorder was observed (p =.009). The PTLD mortality was 5%. There was a change in the PCR level after tacrolimus reduction (p =.002) and after tacrolimus exchange for mTOR (p =.008). The number of EBV copies was significantly higher (p =.029) in patients who developed PTLD. In the multiple regression model, seropositivity for CMV was an independent protective factor for lymphoproliferative disorder (OR=0.09; 95% CI 0.02–0.42), reducing the chance of having PTLD adjusted by serology for EBV by 91%. Conclusions: Monitoring the EBV viral load by PCR seems to prevent the emergence of milder forms of lymphoproliferative disorder. Pretransplant seropositivity for CMV is a protective factor for PTLD. [ABSTRACT FROM AUTHOR]

Background: Corticosteroids have been an integral part of maintenance immunosuppression for pediatric kidney transplantation. However, prolonged steroid therapy is associated with significant toxicities resulting in several SW/avoidance strategies in recent years. Method/Objective: This comprehensive review aims to discuss steroid‐related toxicities and the safety, efficacy, and benefit of steroid avoidance/withdrawal immunosuppression in pediatric kidney transplant recipients. Results: Initial studies of SW/avoidance conducted in the setting of CSA and AZA showed an increased incidence of AR but no increase in graft loss or mortality with SW/avoidance maintenance immunosuppression. Studies performed under modern immunosuppression (induction therapy, Tac, and MMF) show no significant increase in AR or graft loss with SW/avoidance immunosuppression. Furthermore, SW/avoidance immunosuppression is associated with significant improvement in growth, BMI, BP control, and lipid profile in pediatric kidney transplant recipients. Despite these data, SW/avoidance remains controversial, and only 40% of pediatric kidney transplant recipients in the United States are currently on SW/avoidance maintenance immunosuppression. Conclusion: SW/avoidance maintenance immunosuppression is safe and associated with fewer side effects compared with steroid‐inclusive maintenance immunosuppression in pediatric kidney transplant recipients. [ABSTRACT FROM AUTHOR]

Background: Impaired bone mineral density (BMD) and osteoporosis are commonly found in patients who have undergone heart transplantation (HT), which increases the risk for bone fractures which is associated with increased morbidity and mortality in adults. However, the long‐term evolution of BMD after HT in pediatric patients has not been thoroughly investigated. Method: Bone mineral density up to 10 years after HT was investigated in 30 patients who underwent HT at an age <20 years at Skåne University Hospital in Lund 1988–2016. Results: The total observed time was 235 person‐years. Before HT, 86% had low BMD for chronologic age in the lumbar spine. In lumbar spine, BMD was significantly lower than normal for chronological age before HT (p =.034), but recovered at the 4th year (p =.009). In whole body, BMD was normal at the 4th annual check‐up (p =.030) and remained so throughout the follow‐up period. The median T score in the lumbar spine and femoral neck 10 years after HT did not differ between the two groups based on age at HT (<20 years vs 20 years or older; p =.779 in the lumbar spine and p =.388 in the femoral neck). Conclusions: Patients who undergo HT at an age of <20 years have low BMD for chronological age already before HT, but BMD may recover completely within the first 4 years after HT. The results indicate no difference in BMD at 10 years after HT between pediatric and adult patients. [ABSTRACT FROM AUTHOR]

Background: The delivery of healthcare services by telemedicine decreases costs of traveling for patients, is less time‐consuming, and most importantly permits the connection between highly skilled specialists and patients. However, whether the use of telemedicine (text messaging) for LT patients was affected by the COVID‐19 pandemic is unknown. Methods: We collected data (following consent from patients and parents) from 57 patients (33 male/24 female) with a median age of 47 (IQR: 9–91) months, whom we followed up with text messaging between September 2019 and September 2020, spanning the 6 months prior to COVID‐19 and during this period. Results: In total, 723 text message mediated consultations occurred during this period, henceforth simply referred to as "messages." Three hundred and twenty‐eight (45%) messages occurred during the 6 months up to the start of the pandemic. Following the COVID‐19 outbreak, the number of messages increased to 395 (55%). The three most common reasons of messaging were post‐liver‐LT follow‐up messages (n = 215/723, 29.7%), consultations for drug use (n = 157/723, 21.7%), and medication prescriptions (n = 113/723, 15.6%). Protocol biopsy discussions (n = 33/723, 4.6%) and fever (n = 27/723, 3.7%) were among others (vaccination, rash, diarrhea, cough, fatigue, acne). During the COVID‐19 outbreak, only post‐LT follow‐up messages increased significantly to 132/395 (33%) from 83/328 (25%) (p‐value:.02). Conclusions: We found that the pandemic resulted in an increase in the total number of text message mediated consultations and specifically for the use of post‐LT follow‐up. Messaging was effective for post‐LT follow‐ups and all patients were at least satisfied. [ABSTRACT FROM AUTHOR]

Background: CNI‐free immunosuppression with conversion to mTORi‐based immunosuppression has been demonstrated to reduce CNI‐toxicity and to exhibit anti‐proliferative properties. However, the experience of CNI‐free immunosuppression in paediatric heart transplantation is limited. Methods: A retrospective analysis was conducted of 129 paediatric heart transplants performed between 1997 and 2015. Fifteen patients with clinically indicated conversion from CNI‐based to CNI‐free immunosuppression were identified. Survival data, rejection episodes, renal function, post‐transplantation lymphoproliferative disorder and CAV, including examination with OCT were analysed. Results: Immunosuppression conversion was successful in all patients. Fourteen of 15 patients (93%) are currently living with good graft function. Median post‐transplant survival was 15 years (range, 5–23 years), and median follow‐up since conversion was 6 years (range, 1–11 years). Mild (grade 1R) ACR was present in three patients after discontinuation of CNIs. The recovery of renal function with a significant increase in eGFR was observed at 1 and 3 years after conversion. No patient had angiographic signs of macroscopic CAV according to the current ISHLT classification; however, OCT showed the signs of angiographically silent CAV in all patients. CAV did not progress in any patient, implying CAV was stabilised by mTORi‐based CNI‐free immunosuppression. Conclusions: CNI‐free immunosuppression based on mTORis is a safe and appropriate strategy for maintenance therapy in selected paediatric patients, significantly improves renal function and stabilises CAV. OCT revealed early development of angiographically silent CAV. [ABSTRACT FROM AUTHOR]

Background: In 2019, SARS‐CoV‐2 causing COVID‐19 emerged. Severe COVID‐19 symptoms may evolve by virtue of hyperactivation of the immune system. Equally, immunocompromised patients may be at increased risk to develop COVID‐19. However, treatment guidelines for children following liver transplantation are elusive. Methods: As a liver transplantation center, we diagnosed and followed up 10 children (male/female: 8/2) with a median age of 8.5 years (IQR: 5.2–11.0), with COVID‐19 post‐liver transplant between March 2019 and December 2020. COVID‐19 diagnosis was based on PCR test and or florid X‐ray findings compatible with COVID‐19 in the absence of other cause. We retrospectively collected clinical and laboratory data from electronic patient records following written consent from patients/parents. Results: Nine patients were diagnosed as definitive (PCR positive) with one patient being diagnosed as probable COVID‐19. Seven patients recovered without any support whereas three were admitted for non‐invasive oxygenation. Lymphopenia and/or high levels of serum IL‐6 were detected in four patients. Six patients mounted anti‐SARS‐CoV‐2 antibodies at median 30 days (IQR: 26.5–119.0) following COVID‐19 diagnosis. Antibiotic therapy, favipiravir, anakinra, and IVIG were used as treatment in 4,1,1 and 2 patients, respectively. Furthermore, we kept the tacrolimus with or without everolimus but stopped MMF in 2 patients. Importantly, liver allograft function was retained in all patients. Conclusions: We found that being immunocompromised did not affect disease severity nor survival. Stopping MMF yet continuing with tacrolimus was an apt treatment modality in these patients. [ABSTRACT FROM AUTHOR]

Advances in immunosuppression have improved graft survival in pediatric kidney transplant recipients; however, treatment‐related toxicities need to be balanced against the possibility of graft rejection. Several immunosuppressive agents are available for use in transplant recipients; however, the optimal combinations of agents remain unclear, resulting in variations in institutional protocols. Lymphocyte‐depleting antibodies, specifically ATG, are the most common induction agent used for pediatric kidney transplantation in the US. Basiliximab may be used for induction in immunologically low‐risk children; however, pediatric data are scarce. CNIs and antiproliferative agents (mostly Tac and mycophenolate in recent years) constitute the backbone of maintenance immunosuppression. Steroid‐avoidance maintenance regimens remain controversial. Belatacept and mTOR inhibitors are used in children under specific circumstances such as non‐adherence or CNI toxicity. This article reviews the indications, mechanism of action, efficacy, dosing, and side effect profiles of various immunosuppressive agents available for pediatric kidney transplantation. [ABSTRACT FROM AUTHOR]

Background: LAVV have historically been avoided in children after solid organ transplantation. However, it has been reported that post‐transplant, children without severe immunosuppression can generate anti‐varicella antibody after immunization but the duration of the response is not clear. Furthermore, the origin of the varicella virus in immunosuppressed patients who develop varicella after vaccination is often unclear. Clinical progress: A female child received LAVV 30 months after a living donor liver transplant at the age of 2 months. Varicella rash appeared on the trunk 16 days after vaccination and gradually spread over the body. The patient was treated with intravenous acyclovir followed by oral therapy and recovered fully. The virus detected in blisters was derived from the vaccine‐type strain. Paired sera before and after the onset of varicella showed an increase in antibody titer. However, 2 years after onset, the antibody titer decreased to undetectable again. Conclusions: This was an informative case of varicella due to vaccine strain attenuated virus. Antibody levels were not maintained over many years. Although varicella was caused by the vaccine‐type strain, repeated vaccinations may be necessary for post‐transplant patients who develop varicella. [ABSTRACT FROM AUTHOR]

Background: EPP is characterized by photosensitivity and by liver disease. When LT is performed in EPP, recurrence often occurs in the allograft due to ongoing protoporphyrin production in bone marrow. Therefore, curative treatment requires allogeneic HSCT after LT. Long‐term immunosuppression could be spared by using the same donor for both transplants. Methods: A 2‐year‐old girl with EPP in liver failure underwent liver transplant from her father. Transfusion and apheresis therapy were used to lower protoporphyrin levels before and after liver transplant. Ten weeks after liver transplant, she underwent HSCT, using the same donor. Conditioning was with treosulfan, fludarabine, cyclophosphamide, and ATG. GVHD prophylaxis was with abatacept, methotrexate, MMF, and tacrolimus. We followed the patient's erythrocyte protoporphyrin and liver and skin health for 2 years after transplant. Results: After hematopoietic stem cell engraftment, a decline in protoporphyrin levels was observed, with clinical resolution of photosensitivity. Liver biopsies showed no evidence of EPP. Mild ACR occurred and responded to steroid pulse. Two years post‐HSCT, the patient has been weaned off all immunosuppression and remains GVHD and liver rejection free. Conclusions: Sequential liver and HSCT from the same haploidentical donor are feasible in EPP. This strategy can allow for discontinuation of immune suppression. [ABSTRACT FROM AUTHOR]

Background: Post‐transplant lymphoproliferative disease (PTLD) is a life‐threatening complication in renal transplant recipients. Immunomodulatory and chemotherapeutic treatment potentially affect allograft function. The aim of this study was to evaluate graft function of pediatric kidney transplant recipients following diagnosis and standardized treatment of PTLD. Methods: Patients were identified from the German Ped‐PTLD registry, and data on renal function were retrospectively retrieved from patient charts. For PTLD treatment, immunosuppressive therapy was reduced and all children received rituximab (375 mg/m2) for up to six doses. Two patients required additional low‐dose chemotherapy. Renal allograft function was monitored by consecutive measurements of estimated glomerular filtration rate (eGFR) at defined time points. Follow‐up was up to 60 months after PTLD. Results: Twenty patients were included in this cohort analysis. Median time from transplantation to PTLD was 2.4 years. Histopathology showed monomorphic lesions in 16 and polymorphic in 4 patients. Two patients experienced PTLD relapse after 2 and 14 months. Range‐based analysis of variance showed stable allograft function in 17 of 20 patients (85%). Mean eGFR increased during early treatment phase. One patient experienced graft rejection 5.3 years after diagnosis of PTLD. Another patient developed recurrence of primary renal disease (focal‐segmental glomerulosclerosis) and lost his renal allograft 3.8 years post‐transplant (2.0 years after PTLD diagnosis). Conclusion: Treatment of PTLD with rituximab with or without low‐dose chemotherapy in combination with reduced immunosuppression, mostly comprising of an mTOR inhibitor‐based, calcineurin inhibitor‐free regimen, is associated with stable graft function and favorable graft survival in pediatric renal transplant patients. [ABSTRACT FROM AUTHOR]

Background: While operational tolerance has been previously described in isolated intestinal transplant, reports of this phenomenon in combined liver‐intestine transplant are lacking. Case Description: We detail a unique case of a patient who received a composite allograft including liver, pancreas, and small bowel due to short gut syndrome secondary to gastroschisis complicated by volvulus. The indication for transplantation was permanent dependence on total parenteral nutrition, end‐stage liver disease, recurrent sepsis, and persistent stomal variceal hemorrhage. The patient developed severe graft‐versus‐host disease with grade 3 skin involvement, ophthalmic, and pulmonary involvement with 53% donor T‐cell chimerism. She required aggressive therapy including high‐dose methylprednisolone, rituximab, cyclophosphamide, and alemtuzumab. Due to infection concerns following depletion of her lymphocytes, immunosuppression was discontinued with close surveillance of her allograft. Nearly 10 years later, the patient has continued off all immunosuppression without evidence of rejection or graft dysfunction and demonstrates immunocompetence with normal functional immune assays and development of appropriate live vaccination titers. Conclusion: This report of operational tolerance following pediatric composite liver‐pancreas‐intestine transplantation provides evidence that the complex immunologic balance in intestinal transplantation may on rare occasions favor immunosuppression reduction or even discontinuation. Future trials of immunosuppression minimization in this population may be warranted. [ABSTRACT FROM AUTHOR]

Background: Successful renal transplantation requires complex medication regimens that rely on strict adherence to be effective. Variability in immunosuppression exposure, specifically tacrolimus, is associated with poor allograft outcomes. Wide intra‐patient variability of tacrolimus trough concentrations (Vtac) is likely, in part, attributable to regimen complexity and poor medication adherence. Once‐daily tacrolimus formulations create opportunity to simplify therapeutic regimens, and this study aims to evaluate their impact on Vtac and ultimately transplant outcomes. Methods: This retrospective cohort study investigated stable (AYA) renal transplant recipients converted from (IR‐Tac) to (ER‐Tac). Subjects served as their own controls. Vtac was assessed by measuring the (SD) of serial tacrolimus trough concentrations prior to and at four time points post‐conversion to ER‐Tac over 24‐month follow‐up. Secondary outcome measures included graft function, infection rates, and effect on modifiable treatment‐related factors. Results: Twenty‐eight AYA subjects were converted from IR‐Tac to ER‐Tac. Vtac significantly improved following conversion and was sustained for 24 months (Vtac0 2.32 vs. Vtac24 1.11, p.017). Renal function remained stable, and (BPAR) rates were modest (14%). Mean pill burden was reduced by 15%, and 42.9% of subjects achieved a once‐daily medication regimen. Conclusions: Conversion from IR‐Tac to ER‐Tac in this AYA population significantly improved Vtac with sustained effect over 2 years. This effect is likely attributable in part to simplification of the medication regimen and presumably improved medication adherence. Such conversion does not appear to compromise graft function for at least 2 years post‐conversion. [ABSTRACT FROM AUTHOR]

ER‐Tac, taken once per day, is associated with improved adherence. This study examined the potential patient and clinical factors that influence clinicians to convert pediatric patients from immediate‐release to ER‐Tac. This prospective multi‐center observational study followed Canadian pediatric kidney transplant recipients up to 5 years post‐transplant. Cox Proportional Hazards Regression was used to examine the influence of factors on conversion to ER‐Tac. Sixty‐six participants were included in this analysis. For every additional year of age at the time of transplant, the likelihood of conversion was more than doubled (HR 2.54, CI 1.83, 3.54, P < 0.001). The impact of age reduced by three percent for every month after transplant (HR 0.97, CI 0.95, 0.98, P < 0.001). Girls were more likely to be converted than boys (HR 3.78, CI 1.35, 10.6, P 0.01). Adherence measures (MAM‐MM and tacrolimus trough variability), individual barriers to adherence, renal function, HLA mismatch, and rejection were not significant predictors of conversion in the final regression model. ER‐Tac was preferentially prescribed to older age and female patients. Female sex and adolescence are both associated with worse graft outcomes, but we found no link between individualized markers of adherence/graft risk and conversion. Clinicians appeared to be using demographic features to distinguish patients at perceived higher risk and converted accordingly, without a case‐by‐case evaluation of who is more susceptible to poor outcomes. [ABSTRACT FROM AUTHOR]

Background: We studied the association of induction immunosuppression and pediatric deceased‐donor kidney recipient and graft survival. Methods: We utilized the SRTR to evaluate all primary pediatric deceased‐donor kidney transplants from January 1st, 2000, through December 2018. We included only recipients who were maintained on tacrolimus and mycophenolate. Recipients were grouped by induction type: alemtuzumab n = 320, r‐ATG n = 2091 and IL‐2RA n = 2165. Recipient and allograft survival, and their predictors, were examined. Models were adjusted for age, sex, ethnicity, HLA‐antigen mismatches, transplant year, steroid maintenance, pre‐emptive transplantation and payor type, with the transplant center included as a random effect. Results: Rejection rates at 6 months (alemtuzumab 8.6% vs r‐ATG 7.8% vs IL2‐RA 9.2%; P =.30) and 12 months (alemtuzumab 17.2% vs r‐ATG 15.7% vs IL2‐RA 16.5%; P =.70) were not significantly different between induction groups. In the multivariable models, compared to IL‐2RA neither alemtuzumab nor r‐ATG was associated with improved recipient [alemtuzumab (HR 1.06, P =.88); r‐ATG (HR 1.03, P =.84)] or graft survival [alemtuzumab (HR 1.18, P =.32); r‐ATG (HR 1.10, P =.21)]. Conclusion: In this large cohort of standard immunological risk primary pediatric deceased‐donor kidney recipients on tacrolimus and mycophenolate maintenance, depletional induction regimens were not associated with better rejection rates, recipient, or graft survival compared to IL‐2RA induction. Racial, payor type, and sex‐related outcome disparities were significant in this group independent of the induction choice. [ABSTRACT FROM AUTHOR]

Background: Variation in IS exists among pediatric liver transplant centers. While individual centers may publish their practice paradigms, current data on practices as a whole are lacking. This study sought to ascertain the IS protocols of pediatric liver transplant centers within the SPLIT to better understand variability and similarities among peer institutions. Methods: A 27‐item questionnaire was developed within the SPLIT Quality Improvement and Clinical Care Committee. The survey collected data regarding center demographics, IS practices, and treatment of acute cellular rejection. Results: Twenty‐eight (64%) SPLIT centers responded with 22 (79%) centers performing more than 10 transplants per year and 17 (61%) following more than 100 post‐transplant recipients. All centers use a written protocol, and 25 (89%) have a dedicated transplant pharmacist/PharmD. Twenty‐five (89%) centers use steroids for induction alone or in combination with thymoglobulin/interleukin‐2 antibodies. All centers use tacrolimus for initial maintenance therapy. Most centers have specialized protocols for ABO‐incompatible transplants, recipients with renal dysfunction, autoimmune liver diseases, and liver tumors. Treatment of rejection varied but was associated with escalation in IS. Conclusion: IS practices among pediatric liver transplant centers are similar including the use of written protocols, pharmacy involvement, steroids for induction, tacrolimus as initial IS, tacrolimus reduction/delay for renal dysfunction, and escalation of IS with rejection severity. However, other IS practices show wide variability including treatment for ABO‐incompatible grafts and presumed rejection. This study serves as a foundation to guide prospective research linking IS practice to outcomes to determine best practice. [ABSTRACT FROM AUTHOR]

Background: Due to a lack of consensus on SB for pediatric kidney transplant recipients, we evaluated the yield and clinical utility of SB findings at various time points post‐transplant. Methods: Patients transplanted at a single institution between 2014 and 2020 with at least one SB at 1.5, 3, 6, 12, and 24 months post‐transplant were included. Additional biopsies were done for indication (IB). TCMR was classified by Banff criteria (score ≥i1t1). Results: Forty‐seven patients had 142 biopsies (SB = 113, IB = 29); 19 (40.4%) of whom experienced at least one TCMR episode in the first‐year post‐transplant. The greatest SB yield of any pathologic abnormality was at 6 months (57.1%; P <.001). Six months also had the highest yield for TCMR (42.9%), compared with 3.3%, 20.8%, 15.0%, and 9.1% at 1.5, 3, 12 months, and 24 months, respectively (P =.003). SB instigated intensification of immunosuppression (28.3% cases), reduction of immunosuppression (2.7% cases), and other non‐immunosuppressant changes (1.8% cases). The 6‐month SB led to the greatest number of changes in management (53.6%), compared with 1.5, 3, 12, and 24 months (13.3, 20.8, 25.0, and 36.4%, respectively; P =.012). There were no major biopsy‐related complications. Conclusions: SBs identify an important burden of subclinical rejection and other pathology leading to changes in clinical management. The greatest yield was at 6 months, whereas the least utility was at the 1.5 months. Selection of SB timing may be tailored such that the optimal yield is balanced against the procedural risk. [ABSTRACT FROM AUTHOR]

Pediatric transplant recipients are on multiple prescription and non‐prescription drugs. Many patients also use dietary, nutritional, and herbal supplements. This manuscript researched formulations of immunosuppressive drugs currently available and presents information on generic immunosuppressive drugs, commonly used non‐prescription medications, dietary supplements, and herbal supplements. Immunosuppressive drugs are available in various formulations. Not all formulations are interchangeable. A number of FDA‐approved generic formulations are available commercially in the United States. Generally generic formulations produce similar blood concentration vs time profiles compared to brand name products in adults and are considered to be bioequivalent. NSAID should be avoided in transplant patients due to potential drug interactions and increased risk associated with NSAID use; and appropriate doses of acetaminophen should be used for treatment of pain. Over‐the‐counter medications, such as guaifenesin and dextromethorphan, antihistamine medications, including diphenhydramine, loratadine, cetirizine, and fexofenadine, can be safely used in pediatric solid organ transplant population. Many safe and effective over‐the‐counter options exist for stool softening and as laxative. Diarrhea can lead to an increase in calcineurin inhibitor levels. Food can alter the absorption of immunosuppressive drugs. Several herbal products can alter immune status of the patients or alter the blood concentration of immunosuppressive drugs or may produce renal or hepatic toxicities and should be avoided in pediatric transplant recipients. It is important to educate pediatric transplant recipients and their families about not only immunosuppressive drug therapy but also about non‐prescription drugs, dietary, and herbal supplement use. [ABSTRACT FROM AUTHOR]

Background: Immunosuppression is considered a risk factor for more severe clinical presentation of COVID‐19. Limited data regarding clinical outcome exist in adults, whereas very little is known about the spectrum of the disease in pediatric heart transplant recipients. Methods: We retrospectively reviewed the charts of young heart transplant patients from our tertiary care center during the coronavirus pandemic in New York City and identified patients infected with SARS‐CoV‐2. Results: We present four cases with COVID‐19 disease and elaborate on their presentation and clinical course. Conclusions: Although far from conclusive and limited by the small sample size and selection bias, these cases demonstrate mild and self‐limited disease despite immunosuppressive therapy and various comorbidities that are expected to increase the severity of the clinical picture based on extrapolation from the adult experience with this novel disease. [ABSTRACT FROM AUTHOR]

Most children with hepatoblastoma manifest, at the time of LT, a decrease in renal function due to chemotherapy that could be further deteriorated by the use of calcineurin inhibitors. The purpose of this work was to examine the long‐term follow‐up of renal function in a cohort of children transplanted for unresectable hepatoblastoma. We present a retrospective observational study of 10 pediatric patients who received a LT for unresectable hepatoblastoma between 1996 and 2016. All patients included in this study were followed up on a regular basis and were assessed for GFR before transplantation and at least once a year during follow‐up. All patients received standardized chemotherapy treatment for hepatoblastoma and immunosuppression according to hospital protocols. There was a marked decrease in GFR at the time of the LT in five patients presenting renal complications during the pretransplant cycles of chemotherapy. Three patients, one of them with prior kidney involvement, presented complications after LT, namely acute kidney failure and decrease in GFR. Those patients who presented with the lowest GFR at the time of LT eventually recovered renal function at levels similar to the rest of the group on follow‐up. Chemotherapy‐induced nephrotoxicity is a concern in patients treated for hepatoblastoma. Some individuals will develop low GFR after chemotherapy; therefore, strict follow‐up is recommended, as low GFR may affect the doses of subsequent chemotherapy and immunosuppression. Stabilization of GFR levels and occasional improvement can be observed in the post‐transplant period. [ABSTRACT FROM AUTHOR]

Post‐transplant lymphoproliferative disorders (PTLD) are the main malignancy seen after pediatric heart transplant and are a significant cause of morbidity and mortality. Prior to the development of detailed guidelines, we sought to identify trends in screening, diagnosis, and treatment of pediatric PTLD. All Pediatric Heart Transplant Society (PHTS) institutions were surveyed. No identifiable patient information was shared. From 56 PHTS centers, 22 responses were received (39.3%). 100% agree PTLD cannot be diagnosed solely based on elevated Epstein‐Barr virus (EBV) load. All respondents routinely screen for EBV by blood PCR, but frequency of screening varies. There was intermediate consensus regarding the use of computed tomography (CT) and/or positron emission tomography (PET) in surveillance management for PTLD. Most centers require a diagnostic biopsy before initiating new treatment for PTLD (14 of 18, 77.8%), but many reduce immune suppression based on elevated EBV without pathologic PTLD (16 of 22, 72.7%). Beyond immune modulation, rituximab is most commonly used (9 of 13, 69.2%). Consultation with oncology is common (17 of 17, 100%), but timing varies widely. Our survey highlights significant elements of agreement and significant practice variation among PHTS institutions regarding pediatric PTLD. Reduction of immune suppression prior to pathologic diagnosis of PTLD is a common management strategy. When this fails, rituximab is used, but is most often reserved until after confirmation of the diagnosis. Oncology subspecialists are commonly involved in these cases. Our findings highlight the need to develop improved guidelines for evaluation and treatment of pediatric PTLD. [ABSTRACT FROM AUTHOR]

Background: Little data exist on re‐hospitalization rates in pediatric kidney recipients (KTx) particularly with the evolution of transplant immunosuppression. Methods: In a single‐center, retrospective study of pediatric KTx between 2006 and 2016, we assessed re‐hospitalization after KTx admission, stratified by whether the re‐admit was early (<30 days post‐KTx discharge) or late (>30 days), and compared two different immunosuppression eras (one with and one without steroids). Results: Of 197 KTx, 156 (79%) patients were re‐hospitalized in 1st year, 85 (56%) within 30 days of discharge (total 490 1st year re‐hospitalizations). Younger age was associated with early and late re‐hospitalizations. African American race was associated with early re‐hospitalizations. Of the 123 and 74 discharged on steroid‐avoidance (maintenance immunosuppression included MMF in 95%; FK in 50%; CSA in 50%) and steroid‐inclusive (AZA in 66%; MMF in 34%; FK in 30%; CSA in 70%), re‐hospitalization rates, timing post‐transplant, length, and number were not significantly different (P.38;.1;.56;.11). Admission diagnoses analysis demonstrated that steroid‐avoidance recipients had anemia/leucopenia/thrombocytopenia, significantly more often, as one of their admission diagnoses (16% vs 4%; P <.001) and had a rejection diagnosis significantly less often (6% vs 18%; P <.001). Infection diagnoses were not statistically different between groups. Re‐hospitalization, early or late, did not predict worse graft/ patient survival but predicted further hospitalizations. Conclusions: Re‐hospitalization is common after pediatric transplant discharge and predicts further hospitalization regardless of discharge on or off steroids. [ABSTRACT FROM AUTHOR]

Background: LTX in children is associated with increased risk of food allergy, and the mechanisms underlying this are unknown. We wanted to study whether plasma cytokine profile differed in liver transplanted children, with and without food allergy, and whether it differed from untransplanted children with CLD. Methods: Plasma cytokines, total and specific IgE in nine patients with food allergy were compared with 13 patients without food allergy following LTX, and also with seven untransplanted patients with CLD. Results: No difference was found in the cytokine profile between liver transplanted patients with and without food allergy. Transplanted patients with food allergy having received a prescription of epinephrine had a significantly higher total IgE (2033 [234‐2831] vs 10 [5‐41] IU/L, P =.002) and MIP‐1b (52 [37‐96] vs 36 [32‐39], P =.035) compared with transplanted patients without food allergy. Two patients with severe food allergy responded favorably to conversion from tacrolimus‐based immunosuppression to MMF and corticosteroids with reduction in clinical symptoms, total IgE, specific IgE, IL‐1ra, IL‐4, RANTES, PDGF, MIP‐1a, and TNFα. The transplantation group had higher levels of IL‐1b, IL‐5, IL‐7, IL‐13, GCSF, IFNγ, and MIP‐1a compared with the CLD group. Conclusions: No overall difference was found in plasma cytokine profile between patients with and without food allergy. Patients with severe food allergy had significant elevation of MIP‐1b. Discontinuation of tacrolimus reduced total and specific IgE and changed plasma cytokine profile. The plasma cytokine profile in liver transplanted children was different compared with children with CLD. [ABSTRACT FROM AUTHOR]

PTLD is a rare but potentially life‐threatening condition, which shows a higher prevalence in children than in adults. From 129 children who underwent LT, we reported 5 cases with biopsy‐proven PTLD at a single teaching hospital. Four patients had shared clinical presentations including fever, lymphadenopathy, and splenomegaly. They were noted to be given a prolonged course of IS due to the management of comorbid complications such as acute cellular rejection or severe food allergy or eosinophilic gastrointestinal disease. The other one patient presented with upper gastrointestinal bleeding from gastric mass during an early post‐transplantation period. Notably, hypoalbuminemia was noted in all reported patients. Similar to previous studies, both EBV serology mismatch between the donor and recipient with high EBV viral load were noted in all except one case, whose EBV serology was unknown before LT. At least one episode of CMV reactivation was also observed in 3 of 5 patients prior to the PTLD diagnosis. The histopathology revealed 1 of 5 early PTLD, 1 of 5 polymorphic PTLD, and 3 of 5 monomorphic PTLD. The treatment included IS withdrawal, chemotherapy, and/or rituximab. One patient died of multiorgan dysfunction, one remains in complete remission, and three patients are either still on treatment or await response evaluation. Even though most of our reported PTLD cases had shared manifestations with fever, lymphadenopathy, splenomegaly, EBV serology mismatch, and high EBV viral load, various initial presentations such as respiratory symptoms, hypoalbuminemia, and prolonged use of IS from other causes such as significant food allergy were noted. [ABSTRACT FROM AUTHOR]

OS of tacrolimus prepared from tacrolimus powder is not licensed for children. A licensed GF for OS allows flexibility for body weight‐based dose adjustments. This study aimed at exploring the efficacy of conversion from OS to the GF of tacrolimus in stable pediatric renal transplant recipients. Records of 25 pediatric renal transplant recipients aged under 18 years who were switched from an unlicensed tacrolimus OS to GF were reviewed. At day 0, 1 week, and 4‐8 weeks post‐conversion, there were no differences regarding daily tacrolimus dose (3.4 ± 3 vs 3.5 ± 2.9 vs 3.5 ± 2.9 mg/day), trough tacrolimus levels (4.5 ± 2.7 vs 4.2 ± 2.7 vs 4.4 ± 3.1 ng/mL), dose‐normalized trough tacrolimus levels (1.7 ± 1.1 vs 1.5 ± 1.0 vs 1.7 ± 1.3 ng/mL/mg), PCr (65.6 ± 29.4 vs 67.9 ± 30.4 vs 69.8 ± 27.9 μmol/L), and eGFR (73 ± 24.9 vs 68.7 ± 20.2 vs 65.5 ± 18.2 mL/min/1.73 m2) (P > .05). GF dose adjustment was required in 52% of participants. Eighty‐eight percent of patients had to return for repeat tacrolimus levels following dose modifications, generating 33 extra visits (≥2 extra visits for 1/3 of subjects). No rejection episodes occurred in the year after conversion. In conclusion, conversion from tacrolimus OS to GF in stable pediatric renal transplant recipients is safe and efficacious. However, close therapeutic drug monitoring in the immediate post‐conversion period is necessary. [ABSTRACT FROM AUTHOR]

Histological abnormalities, including chronic hepatitis, fibrosis, and steatosis, are increasingly reported in liver biopsies of children after LT. These changes may be progressive and represent a form of rejection. Liver biochemistry is often initially normal. Our LT program began in 2002, utilizing tacrolimus and low‐dose steroids for the first year post‐LT. Patients undergo a protocol biopsy at 1 year post‐LT prior to stopping steroids, then at 5 years and every 5 years thereafter. Target tacrolimus levels are 5‐8 μg/L and 3‐5 μg/L after 3 and 12 months, respectively. Between 2002 and 2009, 51 LT were performed; 50 (98%) and 49 (96%) patients survived for 1 and 5 years, respectively. A total of 43 patients (median age at LT 2.3 years) underwent a protocol biopsy at 1 year (16 male; median time post‐LT 12.5 months), and 44 (20 male; median time post‐LT 5.1 years) at 5 years. By 5 years, 3 had transferred to adult services; 1 was re‐transplanted for graft failure and 1 moved overseas. Biopsies were reviewed by 2 pathologists. Most patients (31/44) were on tacrolimus monotherapy at 5 years. At 1 and 5 years, 29 of 43 (67.5%) and 31 of 44 (71%) biopsies were normal, respectively. Two of 44 had chronic allograft hepatitis at 5 years. Two of 43 and 1 of 44 had isolated fibrosis, 3 of 43 and 3 of 44 steatosis, and 3 of 43 and 4 of 44 acute rejection at 1 and 5 years, respectively. Other findings included predominantly biliary changes (6/43 & 3/44 at 1 and 5 years, respectively). Tacrolimus levels at 5 years were slightly higher than anticipated (median trough level 5.8 μg/L). With an immunosuppressive regimen of tacrolimus and low‐dose steroids for 1 year followed by tacrolimus monotherapy thereafter, the majority of PLB were normal and no progressive changes were observed at 5 years. Compared to other LT programs, we have lower rates of chronic allograft hepatitis, steatosis, and fibrosis at 5 years. However, the tacrolimus levels at 5 years were higher than planned and this may have played a role. Further evaluation is also required to determine the potential long‐term adverse effects of corticosteroid use on linear growth and bone mineral density. [ABSTRACT FROM AUTHOR]

Intestinal transplantation is a successful treatment for children with intestinal failure, but has many potential complications. PTLD, a clinically and histologically diverse malignancy, occurs frequently after intestinal transplantation and can be fatal. The management of this disease is particularly challenging. The rejection‐prone intestinal allograft requires high levels of immunosuppression, a precondition for PTLD. While EBV infection clearly plays a role in disease pathogenesis, the relatively naïve immune system of children is another likely contributor. As a result, pediatric intestine recipients have a higher risk of developing PTLD than other solid organ recipients. Other risk factors for disease development such as molecular and genomic changes that precipitate malignant transformation are not fully understood, especially among children. Studies on adults have started to describe the molecular pathogenesis of PTLD, but the genomic landscape of the malignancy remains largely undefined in pediatric intestinal transplant patients. In this review, we describe what is known about PTLD in pediatric patients after intestinal transplant and highlight current knowledge gaps to better direct future investigations in the pediatric population. [ABSTRACT FROM AUTHOR]

HEV infection can lead to chronic hepatitis in immunosuppressed patients; extrahepatic manifestations are rarely seen. Here, we report a 13-year-old renal transplant patient with chronic hepatitis E and renal involvement. Ribavirin therapy led to temporary virus clearance and amelioration of kidney function. However, ribavirin therapy caused severe hyporegenerative anemia, which has so far only been reported in patients treated with a combination of ribavirin and interferon alpha. [ABSTRACT FROM AUTHOR]

Uncontrolled studies suggest a benefit of nitazoxanide for the treatment of norovirus gastroenteritis in immunocompromised individuals. Here, we report the use of nitazoxanide in a 13-year-old male kidney transplant recipient who developed intractable norovirus gastroenteritis. Reduction of immunosuppression was not possible due to refractory TCMR. Administration of oral immunoglobulin and switching from tacrolimus to sirolimus failed to produce a meaningful clinical response. Treatment with a 14-day course of nitazoxanide resulted in prompt resolution of diarrhea as well as clearance of norovirus from the stool despite intense immunosuppression. Nitazoxanide may be considered as an option for the treatment of intractable norovirus gastroenteritis in pediatric transplant patients when reduced immunosuppression is not feasible or other treatment options have failed. Further studies to evaluate the safety and effectiveness of nitazoxanide in immunocompromised children are needed. [ABSTRACT FROM AUTHOR]

Abstract: Controversy exists whether NE after LT are more frequently observed in children or adults. We aimed to compare the incidence and outcomes for NE after LT in pediatric and adult recipients. A single‐center cohort study, including all LT between 2001 and 2013, was performed. Definition of NE included impaired consciousness, delirium, seizures, focal neurologic deficit, visual impairment, or slurred speech. A cohort of 443 consecutive LT recipients was included: 307 adults and 136 children. Cumulative incidence of NE was similar between adults 15% (n = 41) and children 16% (n = 20; P = .73) with a complete neurological recovery in 62% and 95% of the patients, respectively (P < .0001). Adults with NE had significantly lower survival (70% vs 76%; P = .015) with a HR of 2.36; this was similarly observed in children (45% vs 66%; HR 2.05, CI 0.66; 6.34). Independent risk factors for NE in adults were pre‐LT ascites, delta sodium, and post‐LT hypomagnesemia, whereas in children pre‐LT encephalopathy ≥II and serum albumin were associated with NE. Although a similar incidence of NE after LT was observed, children were more likely to achieve neurological recovery. Risk factors for the development of NE are difficult to assess in both populations. [ABSTRACT FROM AUTHOR]

Abstract: Alemtuzumab is a humanized mAb targeted to CD52. Alemtuzumab is highly immunosuppressive with the ability to deplete T and B cells (in addition to other immune cell lines). A growing understanding of the PKs, dosing, and timing of administration of alemtuzumab has allowed for the study of its use as a conditioning agent for allogeneic HCT. The highly immunosuppressive properties of the drug are particularly appealing in the setting of non‐malignant HCT, where GVHD provides no clinical benefit and relapse of malignancy is not applicable. In addition, the degree of immune suppression achieved with alemtuzumab has allowed for a reduction in the intensity of myeloablative cytotoxic agents included in some HCT conditioning regimens, allowing for fewer acute and late toxicities. This review paper will provide a comprehensive summary of the mechanism of action, PKs, dosing, and timing of alemtuzumab, a brief description of its use in various allogeneic HCT protocols for non‐malignant conditions and a summary of the data regarding its use for GVHD therapy. The goal of this review was to provide an understanding as to how alemtuzumab might be safely incorporated into HCT conditioning regimens for children with non‐malignant disease, allowing for expanded access to curative HCT therapy. [ABSTRACT FROM AUTHOR]