Impact of the Pediatric ABO Policy Change on Listings, Transplants, and Outcomes for Children Younger Than 2 Years Listed for Heart Transplantation in the United States.

BACKGROUND: We assessed the impact of the liberalized ABO pediatric policy change on candidate characteristics and outcomes for children undergoing heart transplant (HT). METHODS AND RESULTS: Children <2 years undergoing HT with ABO strategy reported at listing and HT from December 2011 to November 2020 to the Scientific Registry of Transplant Recipients database were included. Characteristics at listing, HT, and outcomes during the waitlist and post-transplant were compared before the policy change (December 16, 2011 to July 6, 2016), and after the policy change (July 7, 2016 to November 30, 2020). The percentage of ABO-incompatible (ABOi) listings did not increase immediately after the policy change (P = .93); however, ABOi transplants increased by 18% (P < .0001). At listing, both before and after the policy change, ABOi candidates had higher urgency status, renal dysfunction, lower albumin, and required more cardiac support (intravenous inotropes, mechanical ventilation) than those listed ABO compatible (ABOc). On multivariable analysis, there were no differences in waitlist mortality between children listed as ABOi and ABOc before the policy change (adjusted hazard ratio [aHR] 0.80, 95% confidence interval [CI] 0.61-1.05, P = .10) or after the policy change (aHR 1.2, 95% CI 0.85-1.6, P = .33). Post-transplant graft survival was worse for ABOi transplanted children before the policy change (aHR 1.8, 95% CI 1.1-2.8, P = .014), but not significantly different after the policy change (aHR 0.94, 95% CI 0.61-1.4, P = .76). After the policy change, ABOi listed children had significantly shorter waitlist times (P < .05). CONCLUSIONS: The recent pediatric ABO policy change has significantly increased the percentage of ABOi transplantations and decreased waitlist times for children listed ABOi. This change in policy has resulted in broader applicability and actual performance of ABOi transplantation with equal access to ABOi or ABOc organs, and thus eliminated the potential disadvantage of only secondary allocation to ABOi recipients.

Review on clinician bias and its impact on racial and socioeconomic disparities in pediatric heart transplantation.

This expert review seeks to highlight implicit bias in health care, transplant medicine, and pediatric heart transplantation to focus attention on the role these biases may play in the racial/ethnic and socioeconomic disparities noted in pediatric heart transplantation. This review breaks down the transplant decision making process to highlight points at which implicit bias may affect outcomes and discuss how the science of human decision making may help understand these complex processes.

Let's get physical: Aerobic capacity, muscle strength, and muscle endurance after pediatric heart transplantation.

BACKGROUND: Pediatric heart (HTx) and kidney transplant (KTx) recipients may have lower physical fitness than healthy children. This study sought to quantify fitness levels in transplant recipients, investigate associations to clinical factors and quality of life, and identify whether a quick, simple wall-sit test is feasible as a surrogate for overall fitness for longitudinal assessment. METHODS: Aerobic capacity (6-min walk test, 6MWT), normalized muscle strength, muscle endurance, physical activity questionnaire (PAQ), and quality of life (PedsQL™) were prospectively assessed in transplanted children and matched healthy controls. RESULTS: Twenty-two HTx were compared to 20 controls and 6 KTx. 6MWT %predicted was shorter in HTx (87.2 [69.9-118.6] %) than controls (99.9 [80.4-120] %), but similar to KTx (90.3 [78.6-115] %). Muscle strength was lower in HTx deltoids (6.15 [4.35-11.3] kg/m2) and KTx quadriceps (9.27 [8.65-19.1] kg/m2) versus controls. Similarly, muscle endurance was lower in HTx push-ups (28.6 [0-250] %predicted), KTx push-ups (8.35 [0-150] %predicted), HTx curl-ups (115 [0-450] %predicted), and KTx wall-sit time (18.5 [10.0-54.0] s) than controls. In contrast to HTx with only 9%, all KTx were receiving steroid therapy. The wall-sit test significantly correlated with other fitness parameters (normalized quadriceps strength R = .31, #push-ups R = .39, and #curl-ups R = .43) and PedsQL™ (R = .36). CONCLUSIONS: Compared to controls, pediatric HTx and KTx have similarly lower aerobic capacity, but different deficits in muscle strength, likely related to steroid therapy in KTx. The convenient wall-sit test correlates with fitness and reported quality of life, and thus could be a useful easy routine for longitudinal assessment.

Paediatric heart transplantation: life-saving but not yet a cure.

In the 1980s, heart transplantation was the first successful treatment for infants born with hypoplastic left heart syndrome. Infants who have required heart transplantation benefit from immunologic "advantages," including long-term survival free from cardiac allograft vasculopathy. Currently ∼ 90% of children undergoing a heart transplant are reaching their first-year anniversary and the clinical practices of paediatric heart transplantation have dramatically improved. These successes are largely attributed to research sponsored by the Pediatric Heart Transplant Study Group, the International Society of Heart and Lung Transplantation and, more recently, the Non-profits Enduring Hearts and Additional Ventures. Despite these successes, the field is challenged to increase progress to achieve long-term survival into adulthood. The wait-list mortality, especially among infants, is unacceptably high often leading to palliative measures that can increase post-transplant mortality. Cardiac allograft vasculopathy remains a major cause for progressive graft loss of function and sudden death. The relative tolerance seen in immature recipients has not been translated to modifying older recipients' post-transplant outcomes. The modifiable cause(s) for the increased risks of transplantation in children of different ethnicities and races require definition. Addressing these challenges faces the reality that for-profit research favours funding adult recipients, with ∼ 10-fold greater numbers, and their more modest longevity goals. Advocacy for funding "incentives" such as the Orphan Drug rules in the United States and upholding principles of equity and inclusion are critical to addressing the challenges of paediatric heart transplant recipients worldwide.

Successful ABO incompatible heart transplantation after desensitization therapy in an older child.

BACKGROUND: ABO-incompatible heart transplantation (HTx) has become a standard procedure for children below 2 years of age due to an immunologically immature immune system and associated low isohemagglutinin titers. METHODS: We report a case of an ABO-incompatible HTx (recipient blood group O, donor blood group A) at the age of 5 years and 11 months with a fully matured immune system and previously high isohemagglutinin titers that diminished as a result of human leucocyte antigen (HLA) desensitization therapy with rituximab and immunoglobulins. RESULTS: The anti-A titer at the time of HTx was 1:16 with post-transplant isoagglutinin titers never exceeding 1:4 without any signs of rejection with now 3 years of post-HTx follow-up. CONCLUSIONS: ABO isohemagglutinin titers should be routinely assessed in children undergoing desensitization therapy since ABOi transplantation can be considered in selected cases to expand the donor pool with the option of crossing the ABO barrier to find a better-matched allograft.

Differences in medication adherence by sex and organ type among adolescent and young adult solid organ transplant recipients.

BACKGROUND: Identification of differences in medication adherence by sex or organ type may help in planning interventions to optimize outcomes. We compared immunosuppressive medication adherence between males and females, and between kidney, liver and heart transplant recipients. METHODS: This multicenter study of prevalent kidney, liver and heart transplant recipients 14-25 years assessed adherence 3 times (0, 3, 6 months post-enrollment) with the BAASIS self-report tool. At each visit, participants were classified as adherent if they missed no doses in the prior 4 weeks and non-adherent otherwise. Adherence was also assessed using the coefficient of variation (CV) of tacrolimus trough levels; CV < 30% was classified as adherent. We used multivariable mixed effects logistic regression models adjusted for potential confounders to compare adherence by sex and by organ. RESULTS: Across all visits, males (n = 150, median age 20.4 years, IQR 17.2-23.3) had lower odds of self-reported adherence than females (n = 120, median age 19.8 years, IQR 17.1-22.7) (OR 0.41, 95% CI 0.21-0.80) but higher odds of adherence by tacrolimus CV (OR 2.50, 95% CI 1.30-4.82). No significant differences in adherence (by self-report or tacrolimus CV) were noted between the 184 kidney, 58 liver, and 28 heart recipients. CONCLUSION: Females show better self-reported adherence than males but greater variability in tacrolimus levels. Social desirability bias, more common in females than males, may contribute to better self-reported adherence among females. Higher tacrolimus variability among females may reflect biologic differences in tacrolimus metabolism between males and females rather than sex differences in adherence. There were no significant differences in adherence by organ type.

Organ Donation in Canadian PICUs: A Cross-Sectional Survey, 2021-2022.

OBJECTIVES: To understand contemporary pediatric organ donation programs in Canadian PICUs, including: policies and practices, data collection and reporting, and system and process barriers. DESIGN: A cross-sectional survey carried out 2021-2022. SETTING: Canadian PICUs affiliated with a donor physician network. SUBJECTS: Pediatric intensivists identified as the donation program lead, or most knowledgeable about donation for their institution. MEASUREMENTS AND MAIN RESULTS: A 19-item survey was developed through collaboration with stakeholders from the organ donation and transplantation community within Canada. Domains and items were generated and reduced iteratively during an in-person workshop. Pretesting and pilot testing were completed to ensure readability, flow, clinical sensibility, and construct validity. Fifteen of 16 (94%) invited Canadian PICUs from seven provinces completed the survey representing 88% (15/18) of all noncardiac Canadian PICUs. Surveys were completed between June 2021 and September 2022. All units support donation after death by neurologic criteria (DNC); 14 of 15 indicated donation policies were in place and 1 of 15 indicated no policy but the ability to facilitate donation. Thirteen of 15 units (87%) support donation after death by circulatory criteria (DCC) with policies in place, with 11 of 13 of these indicating routine support of donation opportunities. The majority (13/15) of units identified a donation champion. Of the 16 identified champions across these centers, 13 were physicians and were registered nurses or nurse practitioners. Eight of 13 units (62%) with donation champions had positions supported financially, of which 5 units came from the Organ Donation Organization and the other 3 came from the provincial health authority. Finally, only 3 of 15 PICU donation programs have a pediatric donation committee with family involvement. Variability exists in identification (including determination of death practices), referral, and approach for donation between units. CONCLUSIONS: Although all Canadian PICUs support donation after DNC donation, and most support donation after DCC, variability exists in the identification, referral, and approach of potential donors. There is a notable lack of family involvement in pediatric donation programs. There are many opportunities for standardization of PICU donation programs which may result in improved rates of pediatric organ donation in Canada.

Patient and care provider inclusion in the development of an educational graphic novel for heart transplanted teenagers.

PURPOSE: Teenagers experience high rates of rejection and organ failure after heart transplantation due to non-adherence to medications, poor transition into adult care, and difficulties communicating with adults including healthcare providers. This project aimed to creatively bridge this gap-including teenage patients, their parents, and healthcare providers in the development of a new resource meant to motivate teenage heart-transplant-patients to take interest and ownership of their long-term health. METHODS: Four teenage heart-transplanted patients, four parents, and three healthcare providers provided insight into relevant content for an educational resource through semi-standardized questionnaires and interviews. Their input guided the style and substance of the resource developed under the supervision of Fine Arts professors and the pediatric heart transplant team. RESULTS: Parents and healthcare providers were concerned about teenagers' health choices and lack of perspective while patients were more bothered by parental nagging and being careful about infections than worrying about post-transplant risks. The resource that was developed therefore used subtlety within a narrative medium: a graphic novel that involved mutant worms, secret plots, and daring escapes, to address identified medical concerns and encouragements without triggering teenage resistance to instruction. CONCLUSION: The discrepancies between the priorities of healthcare providers, parents, and teenage heart-transplant-patients illustrate the significance of basing resource-development on input from the target population. We developed the first graphic novel written for teenage heart-transplant-patients with patient input and interdisciplinary cooperation, using the subtlety of a narrative medium as a model for integrating medical content within an appealing, motivational, patient-centered, and age-appropriate resource.

The experiences of children with a cardiac transplant, their families and health care providers in the COVID-19 pandemic.

BACKGROUND: The COVID-19 pandemic has had deleterious impacts on pediatric patients and families, as well as the healthcare providers who have attended to their care needs. METHODS: In this qualitative study, children with a cardiac transplant, as well as their families and healthcare providers were interviewed to explore the impact of the COVID-19 pandemic on pediatric care, as well as on patients' and their families' daily lives. Participants were recruited from a children's hospital in western Canada. Fifteen caregiving parents of transplanted children, 2 young patients, and 8 healthcare providers participated in interviews. RESULTS: Findings highlighted how families and their healthcare providers experienced pandemic-related shifts. Themes highlighted experiences, which entailed (1) initially hearing about the COVID-19 pandemic; (2) learning about their new reality; (3) adjusting to the pandemic; (4) adjusting to shifts in pediatric services; (5) evolving a view on the future, and (6) offering recommendations for cardiac care in a pandemic. CONCLUSIONS: Study implications emphasize the need to critically reflect on, and advance, methods of helping young patients and their families in pandemic circumstances, and supporting healthcare providers.

Ventricular assist device support following pediatric heart transplantation.

BACKGROUND: VAD support for early graft failure after HTx is a rare event in pediatrics. METHODS: We retrospectively describe our single-center experience with post-HTx VAD support in a cohort of patients transplanted between 01/05 and 12/20. RESULTS: Nine patients underwent VAD insertion in the early post-HTx period [median age 6.1 years (Range 0.3-20.3), median weight 17.6 kg (Range 3.5-65.0), and congenital heart disease (67%)]. Of the nine patients with early graft failure, almost half (44%) were implanted after 2015 and all of these patients had a pre-HTx plan for possible post-transplant VAD insertion. Time to VAD implant was a median of 0 day (Range 0-11). Total time on VAD support was a median of 12 days (Range 3.0-478.0). Two-thirds (n = 6; 67%) of the patients were weaned from support, retransplanted (11%) and two patients died (22%). In all of the patients where post-HTx VAD was anticipated there was 100% survival. CONCLUSIONS: In this small patient series, post-HTx VAD was a useful measure in selected patients especially with pre-HTx planning. However, more shared experiences to verify these findings are needed.

Alterations in the immune phenotype of thymectomized children and the development of atopic disorders after heart transplantation.

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.

Clinical approach to antibody-mediated rejection from the pediatric heart transplant society.

OBJECTIVE: This document is designed to outline the definition, pathogenesis, diagnostic modalities and therapeutic measures to treat antibody-mediated rejection in children postheart transplant METHODS: Literature review was conducted by a Pediatric Heart Transplant Society (PHTS) working group to identify existing pediatric and adult studies on antibody-mediated rejection (AMR). In addition, the centers participating in PHTS were asked to submit their approach to diagnosis and management of pediatric AMR. This document synthesizes information gathered from both these sources to highlight a practical approach to diagnosing and managing a child with AMR postheart transplant. This document may not represent the practice at all centers in the PHTS and serves as a starting point to understand an approach to this clinical scenario.

Mental health impacts of the COVID-19 pandemic on children with underlying health and disability issues, and their families and health care providers.

Objectives: The COVID-19 pandemic has impacted mental health at a population level. Families of children with health vulnerabilities have been disproportionately affected by pandemic-related policies and service disruptions as they substantially rely on the health and social care system. We elicited the impact of the COVID-19 pandemic on children with health and disability-related vulnerabilities, their families, and their health care providers (HCPs). Methods: Children with diverse health vulnerabilities (cardiac transplantation, respiratory conditions, sickle cell disease, autism spectrum disorder, mental health issues, and nearing the end of life due to a range of underlying causes), as well as their parents and HCPs, participated in semi-structured interviews. Data were analyzed using qualitative content analysis in determining themes related to impact and recommendations for practice improvement. Results: A total of 262 participants (30 children, 76 parents, 156 HCPs) were interviewed. Children described loneliness and isolation; parents described feeling burnt out; and HCPs described strain and a sense of moral distress. Themes reflected mental health impacts on children, families, and HCPs, with insufficient resources to support mental health; organizational and policy influences that shaped service delivery; and recommendations to enhance service delivery. Conclusion: Children with health vulnerabilities, their families and HCPs incurred profound mental health impacts due to pandemic-imposed public health restrictions and care shifts. Recommendations include the development and application of targeted pandemic information and mental health supports. These findings amplify the need for capacity building, including proactive strategies and mitigative planning in the event of a future pandemic.

Post-operative fluid overload as a predictor of hospital and long-term outcomes in a pediatric heart transplant population.

BACKGROUND: Pediatric patients undergoing heart transplant have a number of factors predisposing them to become fluid-overloaded, including capillary leak syndrome. Capillary leak and FO are associated with organ injury and may influence both short- and long-term outcomes. This study aimed to 1) determine the extent, timing, and predictors of post-operative FO and 2) investigate the association of FO with clinically important outcomes. METHODS: Between 2000 and 2012, 70 children less than 6 years old had a heart transplant at our institution. This was a secondary analysis of data from an ongoing prospective cohort study. RESULTS: FO, defined as cumulative fluid balance greater than 10% of body weight in the first 5 post-operative days, occurred in 16/70 patients (23%); 7 of these had more than 20% FO. Shorter donor ischemic time and longer cardiopulmonary bypass time were independently associated with increased risk of FO. FO >20% was a statistically significant independent predictor of mortality (P = .005), ventilation time, and PICU length of stay. There was no statistically significant association between identified neurodevelopment domains and FO. CONCLUSIONS: Our single-center experience demonstrates that FO was common after pediatric heart transplant and was associated with worse clinical outcomes. FO is a potentially modifiable factor, and research is needed to better determine risk factors and whether intervention to reduce FO can improve outcomes in pediatric heart transplant patients.

Care processes and structures associated with higher medication adherence in adolescent and young adult transplant recipients.

BACKGROUND: We aimed to identify care processes and structures that were independently associated with higher medication adherence among young transplant recipients. METHODS: We conducted a prospective, observational cohort study of 270 prevalent kidney, liver, and heart transplant recipients 14-25 years old. Patients were ≥3 months post-transplant, ≥2 months post-discharge, and followed in one of 14 pediatric or 14 adult transplant programs in Canada. Patients were enrolled between June 2015 and March 2018 and followed for 6 months. Adherence was assessed at baseline, 3, and 6 months using the BAASIS© self-report tool. Patients were classified as adherent if no doses were missed in the prior 4 weeks. Transplant program directors and nurses completed questionnaires regarding care organization and processes. RESULTS: Of the 270 participants, 99 were followed in pediatric programs and 171 in adult programs. Median age was 20.3 years, and median time since transplant was 5 years. At baseline, 71.5% were adherent. Multivariable mixed effects logistic regression models with program as a random effect identified two program-level factors as independently associated with better adherence: minimum number of prescribed blood draws per year for those >3 years post-transplant (per 1 additional) (OR 1.12 [95% CI 1.00, 1.26]; p = .047), and average time nurses spend with patients in clinic (per 5 additional minutes) (OR 1.15 [1.03, 1.29]; p = .017). CONCLUSION: Program-level factors including protocols with a greater frequency of routine blood testing and more nurse time with patients were associated with better medication adherence. This suggests that interventions at the program level may support better adherence.

Patient-reported outcome measures in pediatric solid organ transplantation: Exploring stakeholder perspectives on clinical implementation through qualitative description.

PURPOSE: Patient-reported outcome measures (PROMs) are standardized instruments used to collect data about the subjective assessment of medical care from the patient perspective. Implementing PROMs within pediatric clinical settings has gained increasing importance as health services prioritize patient-centred pediatric care. This study explores the perspectives of pediatric solid organ transplant patients, caregivers, and healthcare practitioners (HCPs) on implementing PROMs into clinical practice. METHODS: Qualitative description methods were used to elicit stakeholder perspectives. Semi-structured interviews were conducted across five Canadian transplant centres. Purposive sampling was used to obtain maximum variation across age, gender, and transplant program for all participants, as well as discipline for HCPs. RESULTS: The study included a total of 63 participants [patients (n = 20), caregivers (n = 22) and HCPs (n = 21)]. Nearly all participants endorsed the implementation of PROMs to enhance pediatric transplant clinical care. Three primary roles for PROMs emerged: (1) to bring a transplant patient's overall well-being into the clinical care conversation; (2) to improve patient communication and engagement; and, (3) to inform the practice of clinical pediatric transplant care. Insights for effective implementation included completing electronic PROMs remotely and prior to clinical appointments by patients who are eight to 10 years of age or older. CONCLUSIONS: This study contributes to current research that supports the use of PROMs in clinical pediatric care and guides their effective implementation into practice. Future directions include the development, usability testing, and evaluation of a proposed electronic PROM platform that will inform future research initiatives.

Health-related quality of life after pediatric heart transplantation in early childhood.

BACKGROUND: There is limited information about HRQL after pediatric heart transplantation at a young age. METHODS: Prospective follow-up study of children who received a heart transplant at age ≤4 years. HRQL was assessed using the PedsQLTM 4.0 at age 4.5 years. This cohort was compared with healthy children, children with CHD, and with chronic conditions. Peri-operative factors associated with HRQL were also explored. RESULTS: Of 66 eligible patients, 15 (23%) died prior to the HRQL assessment and 2 (3%) were lost to follow-up, leaving 49 patients. Indication for transplantation was CHD in 27 (55%) and CMP in 22 (45%). Median age (IQR) at transplant was 9 (5-31) months. HRQL was significantly lower in transplanted children compared to population norms (65.3 vs 87.3, P < .0001), children with chronic conditions (65.3 vs 76.1, P = .001), and children with CHD (65.3 vs 81.1, P < .0001). Transplanted children with CHD had lower HRQL than those with a prior diagnosis of CMP (59.5 vs 72.5, P-value = .020). Higher creatinine pretransplant and higher lactate post-operatively were associated with lower HRQL. CONCLUSION: Children after heart transplant had significantly lower HRQL, as reported by their parents, than the normative population, children with chronic conditions, and children with CHD.

Self-reported and Accelerometer-Measured Physical Activity in Children With Cardiomyopathy.

PURPOSE: Children with cardiomyopathy are at risk of heart failure with reduced physical activity (PA) as a cardinal manifestation. Clinical assessment of PA in children is challenging due to the limited validity of subjective reports. The aim of the study was to compare accelerometery measurement with parental report and to identify factors associated with movement behavior (PA, sedentary time, steps per day). METHOD: Fifteen patients with cardiomyopathy (mean, 9.7 years; 64% male) were asked to wear an Actigraph GT3X accelerometer in Edmonton, Canada. Demographics, clinical characteristics, parental-reported PA, and health-related quality of life data were also collected. RESULTS: Participants engaged in a median of 38 minutes of moderate-vigorous PA per day with higher levels in boys versus girls (73.9 [25.03, 78.91] vs 4.13 [2.53, 37.67] minutes, P = .03). Children participating in recreational sports showed a higher level of moderate-vigorous PA (73.92 min/d) compared with those who did not participate (73.9 vs 22.7 min/d, P = .05), and positive family outlook on the child's health was associated with less sedentary time (P = .04). CONCLUSION: Accelerometer measurement in children with cardiomyopathy is an achievable and more objective measure of PA compared with parental report alone and highlighted low levels of PA among these children.

Characteristics, risks, and outcomes of post-transplant lymphoproliferative disease >3 years after pediatric heart transplant: A multicenter analysis.

Post-transplant lymphoproliferative disorder (PTLD) is a significant complication after pediatric heart transplantation (HT), occurring in 5%-15% of patients within 3 years. Data >3 years from HT are limited. We sought to describe the prevalence, risk factors, and outcomes of PTLD occurring late (>3 years) after pediatric HT in the Pediatric Heart Transplant Study from 1993 to 2010. Among 3844 primary HT patients, 110 (3%) developed late, nonrecurrent PTLD. The hazard rate for late PTLD was constant at 0.01 events/year out to 20 years after HT. Risk factors for late PTLD were younger age at HT (HR 1.06, P = 0.003) and Epstein-Barr virus (EBV) naivety (HR 1.65, P = 0.02). Survival after late PTLD was 86% and 68% at 1 and 5 years, with nonwhite race (HR 2.27, P = 0.03) and earlier year of HT (HR 1.03, P = 0.04) independently associated with mortality. Acute rejection and infection were both common after late PTLD, occurring in 26% and 34% of patients. The constant late hazard and contribution of EBV to late PTLD suggest that vigilance for development of PTLD, including for EBV conversion, should persist indefinitely after pediatric HT. The reasons for elevated risk of death for nonwhites after late PTLD are unclear and warrant further investigation.

Epstein-Barr virus associated smooth muscle tumors in solid organ transplant recipients: Incidence over 31 years at a single institution and review of the literature.

INTRODUCTION: Epstein-Barr virus (EBV) associated smooth muscle tumors (EBV-SMT) are a rare complication of solid organ transplantation (SOT). Incidence data related to this EBV-SMT are limited. EBV DNA is universally present in these tumors. How these cells get infected with EBV, whether this is a result of primary EBV infection vs reactivation, and how persistent active EBV infection post-transplant influences EBV-SMT pathogenesis remains unknown. METHODS: Among 5006 SOT recipients (474 pediatric, 4532 adult) receiving SOT at our center between Jan 1984 and Dec 2015, three cases of post-transplant EBV-SMT were identified. RESULTS: All cases were pediatric heart transplants who were EBV seronegative prior to transplant, and experienced primary EBV infection with persistently elevated EBV viral loads, despite antiviral therapy. Two are deceased at 3.2 and 0.9 years post-diagnosis, while one remains alive 6.2 years post diagnosis. The overall local incidence of post-transplant EBV-SMT at our institution was 0.7 (95% CI, 0.2-1.7) per 1000 patient years, and 2.6 (95% CI, 0.6-6.7) per 1000 patient years in pediatric heart transplants. A literature review identified 36 pediatric and 51 adult cases of post-transplant EBV-SMT. CONCLUSIONS: We hypothesize that pre-transplant EBV seronegativity, followed by primary EBV infection and persistently high EBV viral loads, represents a unique risk factor for post-transplant EBV-SMT. Pediatric heart transplant recipients were found to be disproportionately affected by post-transplant EBV-SMT at our institution.