Pediatric Solid Organ Transplant Patients Research Articles

Emergency department evaluation of transplanted children with COVID-19

BackgroundChildren usually have an asymptomatic or mild course of SARS-CoV-2 infection, studies in immunocompromised patients have shown a different evolution. The aim of this study was to describe the clinical, laboratory, and radiologic manifestations of pediatric solid organ transplant (SOT) and hematopoietic stem cell transplant (HSCT) patients testing positive for SARS-CoV-2. MethodsA multicenter retrospective, observational descriptive study was conducted in 3 tertiary hospitals in Madrid (Spain) between March 2020 and December 2022. Consecutive patients aged 0–18 attending the corresponding pediatric emergency departments with a positive result in the real-time polymerase chain reaction test or antigenic test to detect SARS-CoV-2 in the nasopharyngeal sample were included. ResultsA total of 31 children were included in the study. Sixteen (51.6%) were patients with HSCT and 15 (48.3) were patients with SOT. The median time from transplantation to COVID-19 was 1.2 years (IQR:0.5–5.1). The SOT cohort included liver (n = 4, 12.9%), kidney (n = 4, 12.9%), heart (n = 3, 9.7%), multivisceral (n = 3, 9.7%), and lung (n = 1, 3.2%). Of the 31 patients, only one was asymptomatic. The most common symptom on presentation was fever (76.7%). Abnormalities were seen on chest X-ray in 8 (66.6%) of the 12 patients. There was no significant difference in clinical manifestations, lymphopenia and radiological findings regardless of the type of transplantation or immunosuppression status. Thirteen patients (41.9%) were hospitalized. There were no patient deaths. ConclusionsIn our study, we found that the clinical course and outcome of SOT and HSCT pediatric patients with COVID-19 were generally favorable.

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

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

A scoping review of pediatric transplant education.

Education is crucial for pediatric patients and caregivers throughout the transplant continuum, yet data are lacking around which interventions are effective and in what circumstances. We undertook a scoping review with the objectives of (a) describing the types, effects, and outcomes of patient-focused educational interventions before and after pediatric transplant and (b) understanding the educational experiences of patients and caregivers. Five scientific databases were explored for relevant literature using the JBI methodology. Educational interventions published in English, targeting pediatric solid organ transplant patients (0-25 years) and their caregivers were included. Relevant data from eligible articles (n = 27) were extracted and summarized. Eighteen articles describing 17 educational interventions were identified for objective A, and nine articles qualitatively assessing patient or parental learning needs were identified for objective B. Most interventions were directed toward teenage patients and their caregivers post kidney transplant, primarily focusing on medication self-management and adherence, or providing general information on transplant using multicomponent delivery formats. Most interventions achieved statistically significant improvements in knowledge (n = 8/9) and patients or caregivers expressed satisfaction with the intervention (n = 7/7) but health-related outcomes such as medication adherence (n = 2/6) or behavior change (n = 1/3) rarely achieved statistically significant results. In objective B, patients and caregivers described the transplant process as overwhelming, but indicated that social supports and education helped them cope. Participants consistently wanted more information than they received. Caregivers and pediatric patients value transplant education, but high-quality studies are limited. Since education is a fundamental part of the transplant process, future research in this area should be prioritized.

#54 Morbidity and Mortality Associated with Respiratory Syncytial Virus (RSV) Among Pediatric Solid Organ Transplant (SOT) Recipients: Preliminary Results from a Multi-Site U.S. Study.

Abstract Background RSV is the most common lower respiratory tract infection (LRTI) among children. Serious adverse outcomes are more likely among immunocompromised patients, including progression to pneumonia, respiratory failure, and increased mortality rates. We present interim analyses results from a secondary data use multi-site study to characterize the morbidity and mortality associated with RSV infection among pediatric SOT patients. Method Pediatric (< 18 years old at transplant) SOT recipients from 10 U.S. transplant centers from the Pediatric Infectious Diseases Transplant Network (PIDTRAN) who underwent SOT between 2010 and 2019 and were RSV positive within 365 days of SOT were identified from medical records. Demographics, underlying condition, and clinical characteristics were abstracted and entered in an electronic REDCap survey. Descriptive statistics were used to characterize the clinical course and outcomes of RSV infection. Results In total, 40 SOT patients were eligible for analysis with 40 (93%) reporting 1 case of RSV within 365 days of transplant and 3 (7%) reported 2 episodes resulting in 43 RSV episodes. Over half (24, 60%) were male, 24 (60%) were white/Caucasian, with a median age of 2 years at the time of RSV diagnosis. The majority received 1 SOT (80%) prior to RSV diagnosis. The most common transplanted organ was liver 17 (42%) followed by heart 14 (36%) and kidney 9 (22%). Among the 43 episodes reported, almost half (46.5%) were diagnosed with LRTI at the time of RSV diagnosis and 29 (67.4%) required hospitalization. Among the 43 episodes, none received palivizumab and 1 (2.3%) received IVIG in the 4 weeks prior to RSV diagnosis. Nearly half (21, 48.8%) received oxygen support at least 4 hours per day (at least one day) with 3 (15%) requiring ventilator support. Only 2 (5%) were treated with ribavirin while 3 (7%) received IVIG within 28 days for the treatment of RSV. None received palivizumab within 28 days of diagnosis for RSV treatment. Among those who initially presented with upper respiratory tract infection, 2 (10%) progressed to LRTI after initial diagnosis of a URTI. One (2.4%) death related to RSV was reported. Conclusion Preliminary results from this continuing multi-site study demonstrate RSV is an ongoing concern among SOT recipients with approximately half developing LRTI and two thirds requiring hospitalization. These data help our understanding of RSV infections in this population and inform future prospective study designs to better define RSV risk as well as help address optimal prophylaxis and treatment strategies for SOT recipients at risk for severe illness.

COVID-19 infection in pediatric solid organ transplant patients.

BackgroundAdult SOT recipients with COVID‐19 have higher mortality rates when compared to general population. There is paucity of data on outcomes in pediatric SOT recipients.MethodsThis is a cross‐sectional study investigating the prevalence of COVID‐19 infection and outcomes in pediatric SOT (heart, liver, and kidney) recipients. We extracted demographic and clinical characteristics and COVID‐19 testing (PCR or [Ab] test) results from medical records. Clinical characteristics were compared between patients who were positive for COVID‐19 (PCR or Ab) and those who did not, using Mann‐Whitney, Student's t test, or chi‐square test. p value <.05 was statistically significant.ResultsA total of 108 SOT recipients with a median age of 13.1 (8.4, 17.8) years and median 4.2 (2.7, 7.9) years from transplant were checked for COVID‐19 via a PCR or Ab test. A positive PCR was confirmed in 10 patients (9.3%), while 12 patients (11.1%) were positive for COVID‐19 Ab. The patients who tested positive in our cohort were 9/50 (18%) heart, 6/68 (8.8%) kidney, and 7/50 (14%) liver transplant recipients. There were no differences in the clinical characteristics between patients with and without COVID‐19 infection. All patients were either asymptomatic (50%) or had self‐limiting symptoms. No changes were made to the immunosuppressive regimen. Only one patient was hospitalized and none had an oxygen requirement.ConclusionsIn our cohort of pediatric SOT recipients, COVID‐19 infection was asymptomatic or mild. This data may aid clinicians in counseling patients and families in this increased‐risk population.

Kidney Outcomes in Pediatric Non-Kidney Solid Organ Transplant Patients

Kidney Outcomes in Pediatric Non-Kidney Solid Organ Transplant Patients

Outcomes of skin cancers in pediatric solid organ transplant patients: A systematic review.

The most frequently reported malignancies after solid organ transplant are cutaneous, but data on the risk in pediatric populations varies across studies. To perform a systematic review including reported features and outcomes of skin cancers in pediatric solid organ transplant recipients. EMBASE and MEDLINE were systematically searched (Prospero CRD42020201659). The review summarizes data from 20studies on 337 patients, with a median age ranging from 15.0 to 19.5years as reported in 4studies, who developed skin malignancies after pediatric solid organ transplantation. Median ages at transplant and skin cancer diagnosis ranged from 1.5 to 17.0years and 15.3 to 33.5years, respectively. Squamous cell carcinoma (SCC) was most commonly reported (218 cases), followed by basal cell carcinoma (BCC) (91 cases), melanoma (18 cases), and unspecified keratinocyte carcinomas (2 cases). The median latency period between transplantation and cancer diagnosis ranged from 2.2 to 21.0years. Overall, 4studies reported 17 cases of metastasis in total, and recurrence was reported in one case. Six deaths were reported in one study related to SCC and melanoma metastases. The incidence rate of skin cancer after pediatric transplantation per 100 person-years of follow-up was 2.1 based on 5studies. The most frequent post-transplant malignancy in pediatric organ transplant recipients was SCC.

Immunologic response of mRNA SARS-CoV-2 vaccination in adolescent kidney transplant recipients.

BackgroundIn the general population, mRNA SARS-CoV-2 vaccines are highly efficacious. Early reports suggest a diminished antibody response in immunosuppressed adult solid organ transplant (SOT) patients, but this has not been reported in pediatrics.MethodsAdolescent kidney transplant recipients (KTR) at our center who received both doses of an mRNA SARS-CoV-2 vaccine had SARS-CoV-2 spike (S) protein antibody presence evaluated 4–8 weeks after their second dose of the vaccine as part of routine clinical care.ResultsThirteen of 25 fully vaccinated patients (52%) had a positive spike antibody. Median age of participants was 19 years old (IQR 18–20) and the median time from transplant was 5 years (IQR 4–9 years). KTR were treated with an immunosuppression regimen including a calcineurin inhibitor, corticosteroid, and antimetabolite (9 with mycophenolate, 3 with azathioprine, and 1 without an antimetabolite due to viremia). Of those who had an antibody response, fewer had a mycophenolate-containing immunosuppressant regimen than non-responders. There was a trend toward better vaccine response and higher anti-S antibody titers at lower doses of mycophenolate. Three patients with prior COVID-19 infection all had a positive antibody response.ConclusionOur results suggest vaccine response in adolescent KRT is lower than that of the general population, but similar to that previously described in adult SOT patients and slightly better than that seen in adult KTR. This data demonstrates vaccination is safe and supports immunizing KTR who remain hesitant. Future studies should focus on better understanding of the cellular immune response to vaccination and strategies to enhance vaccine immunogenicity in pediatric SOT patients.Graphical abstract

Examining the association of medical complications and posttraumatic stress symptoms in pediatric solid organ transplant patients and their caregivers.

Post-traumatic stress symptoms (PTSS) have been reported by pediatric solid organ transplant (SOT) patients and their caregivers well after transplantation. This study examined the relationship between PTSS, medication adherence, and medical complications in SOT patients and their caregivers. A secondary aim examined the association between patient and caregiver-reported PTSS. Pediatric SOT patients (N=69) and caregivers (N=73) reported on PTSS by completing the Child PTSD Symptom Scale (patients 8-17years) or the Impact of Events Scale-Revised (patients 18years and older and caregivers). Patient medication adherence was assessed using the Medication Level Variability Index (MLVI). Patients were dichotomized as experiencing a post-transplant medical complication (ie, transplant-related hospital admission prior to the year completing measures of PTSS) or no complications. Medication adherence was not significantly associated with patient or caregiver PTSS. A moderate effect size was found for elevated young adult and caregiver PTSS and the presence of a medical complication. Generally, the association between self-reported patient and caregiver PTSS was low. The presence of elevated PTSS in young adult patients may be partially explained by the presence of proximal medical complications and more so by comorbid psychiatric diagnoses in child and adolescent patients (based on exploratory analyses). Caregivers of patients with medical complications within the past year reported higher levels of PTSS. Overall, transplantation and its associated impact on PTSS may be unique experience for patients versus caregivers. Qualitative research may further elucidate these experiences and inform future clinical interventions.

Immune profiling of COVID-19 infection in pediatric solid organ transplantation

Abstract Background: We describe the clinical presentation &amp; immune response to COVID-19 infection in pediatric SOT. Method: Medical records of COVID-19 PCR+ &amp; seropositive patients (SP) were reviewed for details of their disease course. Blood was obtained during PCR or seropositivity for immunophenotyping. Controls were pediatric solid organ transplant (SOT) patients with negative COVID-19 (NCs) status. As induction of immunological memory is central to anti-pathogen adaptive immunity induced by infection, immunohistochemistry of liver tissue for tissue resident memory cells (TRM) was performed. Results: 15 patients had COVID positive status (7 PCR+ &amp; 8 SP) between March 2020 &amp; January 2021. 4 symptomatic PCR+ patients were hospitalized for 24–72-hours &amp; 1 symptomatic SP patient had a prolonged PICU stay. Infrequent TRM were seen in liver biopsies of PCR+ &amp; SP patients vs. biopsies from same patients that pre-date a COVID-19+ status. Patients with COVID + status appeared to segregate into 2 groups: 1 group with activated CD4+ response, &amp; the 2nd group lacking obvious activated CD4+ response, similar to NC patients (n=16). The PCR+ patients expressed significantly less CD4+ &amp; CD8+ IFN-γ compared to the SP patients (p=0.009; p=0.01 respectively). Similarly, activated CD8 “EMRAs” was significantly lower in PCR+ patients compared to SP patients (p=0.01). Conclusion: COVID-19 infection in pediatric SOT patients is generally mild with notable increased frequency of CD8+ “EMRAs” &amp; IFN-γ in SP patients, presumably a result of antigen-experienced cells.

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

PurposePatient-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.MethodsQualitative 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.ResultsThe 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.ConclusionsThis 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.

Vaccine-induced protection against hepatitis B in pediatric solid organ transplant patients.

Vaccination against hepatitis B virus (HBV) has led to a worldwide reduction in disease burden and mortality. Vaccine immunogenicity data in transplanted children are limited, and vaccine-induced protection may be reduced. We evaluated HBV vaccination coverage, seroprotection rates, and factors influencing vaccine immunity among pediatric solid organ transplant (SOT) patients. We retrospectively identified patients ≤21years of age evaluated for SOT and/or transplanted at our center between January 1, 2015, and December 31, 2018. A detailed chart review was conducted using a standard questionnaire to gather information on demographic, clinical, and laboratory features of patients' HBV vaccination, and hepatitis B surface antibody (HBsAb) titers. A total of 381 patients undergoing evaluation and/or transplantation were included: 139 (36.5%) liver, 138 (36.2%) kidney, and 104 (27.3%) heart. Overall, HBsAb at evaluation was reactive in 216 (56.7%), indeterminate in 17 (4.5%), non-reactive in 138 (36.2%), and not available in 10 (2.6%). Of those that completed a primary HBV vaccine series (n=304), HBsAb was reactive in 164 (53.9%), indeterminate in 13 (4.3%), non-reactive in 119 (39.1%), and not available in 8 (2.6%). For those up to date for age on HBV vaccinations with non-reactive/indeterminate titers at evaluation, revaccination and a follow-up HBsAb were available in 45 patients of which 33 (73.3%) seroconverted to a reactive HBsAb titer. Vaccine-induced protection against HBV infection among high-risk pediatric SOT recipients can be improved by serology-based intervention. Though the absence of HBsAb does not always indicate loss of protection, boosting or completing primary series is recommended.

Exploring the potential for online peer support mentorship: Perspectives of pediatric solid organ transplant patients.

Self-management for patients who have undergone solid organ transplantation is demanding and a challenge for adolescents transitioning into adult-oriented healthcare systems. This study explores whether adolescent and young adult solid organ transplant patients support the use of online peer support programs that encourage peer mentorship as an approach to improve disease self-management. A qualitative descriptive design comprised of semi-structured interviews with adolescent and young adult transplant patients. Individual interviews were audio-recorded, transcribed verbatim, and subject to content analysis. Emergent categories and themes were refined through member checking and team consensus following saturation. Interviews were conducted across organ groups with 15 participants (60% female) ages 14 to 22years. Participants expressed unanimous support for an online peer support mentorship program to aid disease self-management in the pediatric transplant patient population. Three themes emerged from the interviews: (a) self-management care can be "taxing"; (b) there would be value in peer mentorship for adolescent transplant patients; and (c) online peer mentorship is the "best" option but still requires relationship building. Logistical preferences of an online peer mentorship program were solicited. The preferred peer "match" was someone of the same organ transplant group and gender who was able to have weekly contact via texting. Creating tailored, online peer mentorship programs is gaining evidence to justify further development. Findings from this study will support program modifications for adolescent and young adult solid organ transplant patients. Next steps will involve usability and feasibility testing of an adapted online program for this patient group.

Improving the Care for Pediatric Transplant Patients through Integration of Patient-Reported Outcome Measures into Clinical Practice

Subjective evaluation of medical care and treatment from the patient's perspective is increasingly important. Patient-reported outcome measures (PROMs) are "any report of the patient's health condition that comes directly from the patient, without interpretation of the patient's response by a clinician or anyone else" and can comprise information about symptoms, functional status, and quality of life. PROMs have the ability to engage patients meaningfully, give them a voice in their healthcare, and capture their experiences and attitudes. This study explores the perspectives of pediatric solid organ transplant patients, caregivers and healthcare providers on implementing PROMs into clinical practice. Semi-structured interviews were conducted at five Canadian pediatric transplant centres. Maximum variation sampling was used to provide concurring and confirming data, and ensure saturation. An iterative coding process was applied with constant comparative data analysis to identify themes. A total of 20 patients, 22 caregivers and 20 healthcare providers participated. Nearly all participants (n = 59, 95%) were supportive of implementing PROMs with the primary goals to 1) enhance patient-provider communication - "Opens conversations"; "[Patients] state what they're feeling", and 2) increase patient engagement - "Like you're part of the team". Participants discussed the potential impact of PROMs as the provision of preventative - "You'll be proactive", and holistic care - "You cannot separate medical from other aspects. [Patients] are struggling from a mental health perspective". Participants identified selected PROMs, the PedsQLTM Generic Core Scales - "Covers aspects I wouldn't usually include in my assessment" and the PedsQLTM Transplant Module - "More related to transplant patients". Recommendations included 1) PROM data collection for patients eight years of age and older, 2) remote administration and completion of electronic PROMs, prior to clinical appointments, and 3) visual data representation. Findings highlight support for the implementation of PROMs into pediatric solid organ transplantation. Future research is needed to develop implementation strategies to effectively integrate PROMs into clinical workflow and assess the impact on patient health outcomes.

Variability of Pneumocystis jirovecii prophylaxis use among pediatric solid organ transplant providers.

Pneumocystis jirovecii pneumonia (PJP) prophylaxis after pediatric solid organ transplant (SOT) is routinely recommended, but practice varies. Online survey was sent in 2018 to 707 members of the International Pediatric Transplant Association. A total of 105 responded, representing 47 institutions in 18 countries consisting of transplant physicians (66%), transplant surgeons (19%), nurse practitioners (6%), infectious disease physicians (5%), or pharmacists (4%). PJP prophylaxis was reported by 88%, while 12% did not routinely give prophylaxis. The majority not using PJP prophylaxis performed renal transplants (67%) citing low incidence of PJP (62%). Trimethoprim/sulfamethoxazole was first-line agent (95%). PJP prophylaxis for 4-6months was the most frequent duration following kidney (48%, 27/56), liver (42%, 13/31), and heart (40%, 10/25) transplant. Abdominal multivisceral providers equally gave 10-12months (47%) or lifelong (47%); most lung transplant providers gave lifelong prophylaxis (85%). Across all organs, 21% provided lifetime prophylaxis. After completion of prophylaxis, 32% do not restart for any reason; majority of the rest would restart for treatment of acute graft rejection. 83% reported no PJP cases in the prior 12months; 14% reporting 1-5 infections. Only 3% reported a case of PJP infection on prophylaxis; none in SOT. PJP prophylaxis is routinely provided to pediatric SOT patients though practice and duration vary by center and organ type. Durations of 4-6months were most common for renal, liver, and heart transplant recipients, while 10-12months or lifelong prophylaxis were commonly reported for abdominal multivisceral recipients and most lung transplant recipients are given lifelong prophylaxis.

Digital medicine program with pediatric solid organ transplant patients: Perceived benefits and challenges.

Given the complexity of the pediatric post-transplant medication regimen and known medication adherence difficulties within the solid organ transplant population, interventions to improve adherence continue to be explored and fine-tuned. Advances in technology have led to the development of new programs aimed at improving medication adherence and the overall care of transplant patients. This manuscript describes implementation of a DMP where transplant patients' medications were co-encapsulated with ingestible sensors, and adherence was monitored via a patient mobile application and a provider portal. The benefits and challenges of the DMP as reported by patients, caregivers, and medical providers are explored in this manuscript. Participant feedback regarding best practices highlighted these benefits: ease of use/intuitive technology, sense of improved communication with medical team, increased knowledge and motivation around treatment regimen, and positive self-reports of medication adherence. Challenges included reluctance to participate (n=43, 54.43% of patients approached declined participation) and patch wearability difficulties reported by participants (n=20; 68.97%). Other notable challenges included the following: limited drug profile compatibility with the DMP technology and concerns about privacy and electronic data sharing for patients who chose not to participate. DMP implementation highlighted how technological advances offer novel methods to assess adherence, enhance medical decision-making, and can potentially improve clinical outcomes. Although numerous benefits of the program were recognized by participants, challenges were identified and the DMP technology and medication panel continues to be refined; further investigation of such programs continues to be warranted.

Patient-reported outcome measures within pediatric solid organ transplantation: A systematic review.

Subjective evaluation of medical care and disease outcomes from patients' perspectives has become increasingly important. Patient-reported outcome measures (PROMs) play a prominent role in engaging patients, capturing their experiences and improving patient care. This systematic review sought to identify PROMs that are used in the field of pediatric solid organ transplantation, with the aim to inform the implementation of PROMs into clinical practice for this population. A systematic review of English language, peer-reviewed articles was performed on key health science databases to identify publications using PROMs in pediatric solid organ transplantation. The search yielded 3670 articles, with a final data set of 62 articles that included 47 different PROMs. The three most frequently used PROMs included the following: (a) PedsQL™ Generic Core Scales (n=25); (b) Children's Depression Inventory (n=6); and (c) Child Health Questionnaire (n=6). Of the 47 PROMs, 42 were generic and five were disease-specific; only six PROMS had a documented psychometric evaluation within a pediatric solid organ transplant population. This review outlines the attributes of the instruments (eg, domains captured), as well as the psychometric properties of those evaluated. PROMs are increasingly used in the field of pediatric transplantation; however, there are limited details in the current literature about their conceptual underpinnings and psychometric properties. This review highlights the need for additional psychometric evaluation of identified measures to establish the necessary foundation to inform the implementation of PROMs into clinical care for pediatric solid organ transplant patients.

A Systematic Literature Review of Real-World Evidence in Post-Transplant Lymphoproliferative Disorder

Introduction: Recipients of solid-organ transplant (SOT) or allogeneic hematopoietic stem cell transplantation (HCT) have an increased risk of cancers from Epstein-Barr virus (EBV), specifically lymphomas due to immunosuppression. Post-transplant lymphoproliferative disorder (PTLD) is a disease with a range of clinical presentations, including that of an aggressive lymphoma, that occurs after transplantation. PTLD occurs rarely after transplantation and is associated with poor survival outcomes. Publications on the clinical evidence for PTLD are scarce; therefore, a systematic literature review (SLR) was conducted to better understand the real-world evidence in PTLD.Methods: An SLR was performed following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, with the scope defined in terms of Population, Intervention Comparators, Outcomes and Study design (PICOS) criteria. Studies were identified based on a systematic search using key biomedical literature databases: EMBASE, MEDLINE, and Cochrane. The literature search was conducted on July 19, 2018 and included studies published between database inception in January 1, 1959 and July 19, 2018. Relevant congress abstracts published between January 2015 and June 2018 were also identified. The PICOS-based inclusion and exclusion criteria were used to review identified citations. To ensure inclusion of all relevant evidence, no treatment limitations were imposed; however, the study designs were limited to prospective and retrospective observational studies. Case reports were included regardless of sample size. Two independent reviewers screened all citations and full-text articles; any discrepancies were resolved by a third independent reviewer. Data from included studies were extracted into a pre-defined template, and results were summarized using the PRISMA flow diagram.Results: A total of 447 articles were identified that met the SLR criteria: 350 SOT, 70 HCT, and 27 that included both SOT and HCT. Among 97 studies of PTLD post HCT, 81 involved allogeneic HCT, 2 involved autologous HCT, and 14 did not report the type of HCT. Of the 376 identified studies with PTLD post-SOT, the most prevalent SOTs involved were: kidney (193 studies), heart (126 studies), liver (91 studies), lung (84 studies), pancreas (43 studies), and intestine (25 studies). Data on the risk of PTLD, treatment patterns for PTLD, and utilization and survival outcomes following PTLD were reported in 334, 331, and 210 studies, respectively.There was notable clinical and methodological heterogeneity among studies. For example, there was variability in the study populations: 114 were adult populations, 136 were pediatric populations, and 197 did not specify age. Most of the studies were retrospective (419 studies) versus prospective (28 studies), and most were single-center studies (340 studies) versus multicenter studies/registries (98 studies), limiting the generalizability of the results. In addition, the sample sizes were small among most PTLD studies, with fewer than 50 patients in 376 studies, 50-100 patients in 9 studies, and more than 100 patients in 46 studies. The clinical and methodological heterogeneity noted above may explain the large variations in reported risk of PTLD in both HCT and SOT. Among adult SOT patients, the risk of developing PTLD was 0.2% to 11.5%, while among pediatric SOT patients, the risk was 0.3% to 25.0%. Among adults with HCT, the risk of developing PTLD was 1.0 to 20.0%, while among pediatric patients with HCT, the risk was 1.3% to 23.5%.Conclusions: To the best of our knowledge, this is the first comprehensive SLR to examine the published real-world evidence in patients with PTLD. Our SLR reveals important differences with respect to methodology and reporting of real-world published studies assessing the current landscape in PTLD. Additional large, high-quality studies employing more rigorous study methodology are required to understand the current landscape of PTLD in the real-world setting. DisclosuresXu:Atara Biotherapeutics, Inc: Employment, Equity Ownership. Forsythe:Novartis: Consultancy. Barlev:Atara Biotherapeutics, Inc: Employment, Equity Ownership. Watson:Atara Biotherapeutics, Inc: Employment, Equity Ownership.

1590. A Hybrid CMV Prevention Strategy Is Effective in Preventing CMV Disease Outcomes in Pediatric Solid Organ Transplant Patients

BackgroundOptimal CMV prevention strategies for pediatric solid-organ transplant (SOT) patients have not been clearly defined for early and late post-transplant periods.MethodsWe analyzed CMV prevention strategies in liver, kidney, heart, lung and intestinal SOT patients from 2005 to 2015 in our institution. A hybrid strategy was defined as prophylaxis for ≤6 months post-transplant and then transition to a pre-emptive strategy.ResultsOf 833 patients, 769 were prophylaxis and 62 were hybrid strategies. Compared with prophylaxis, hybrid patients were more likely to have a D−/R− CMV serology status, be ≤1 year old and have a heart transplant (P < 0.001). We found no significant differences in CMV disease frequency, rejection or mortality between hybrid and prophylaxis groups. In total, we found 13 cases of CMV disease, of which 1 was a hybrid and the rest a prophylaxis strategy. The median time to CMV disease was 1.5 years from transplant. We found more allograft rejection (n = 9) in patients with CMV disease compared with patients with CMV infection or no Infection. For the same comparisons, no significant difference was found for age or type of organ transplant. Late rejection was frequent (n = 6/13, 67%) in patients with CMV disease, and the majority were not started on empiric anti-virals with the rejection episode. In contrast, no CMV disease was found in patients who had late rejection and received empiric anti-viral with the rejection episode, even though these patients had increasing CMV DNAemia (P = 0.04).ConclusionIn the early post-transplant period, a hybrid CMV prevention strategy is effective with similar clinical outcomes compared with a prophylaxis strategy, even in younger CMV naïve patients and relatively more immune suppressed heart transplant patients. A hybrid strategy may provide effective long-term control of intermittent CMV replication as suggested by the low frequency of CMV disease in this group compared with prophylaxis. In the late post-transplant period, administering episodic empiric anti-virals with a rejection diagnosis may be necessary to prevent CMV disease associated with late rejection episodes.Disclosures All authors: No reported disclosures.

2484. Pre-Transplant Vaccination Adherence in Pediatric Solid Organ Transplant Patients at a Large Academic Medical Center

BackgroundAdherence rates for recommended pre-transplant (pre-txp) vaccinations in pediatric solid-organ transplant (SOT) patients are variable and practice-dependent. Cleveland Clinic Children’s Hospital (CCCH) pre-txp adherence rates for select vaccines have not been described. The purpose of this study was to evaluate pre-txp adherence rates for the following vaccines: hepatitis B, influenza, pneumococcal conjugate (PCV13), pneumococcal polysaccharide (PPSV23), and hepatitis A (if at-risk).MethodsThis retrospective cohort study included patients undergoing initial pediatric heart, kidney, liver, or intestine/multi-visceral transplant at CCCH between 1/1/14 and 7/31/17. Data collected from the electronic medical record and Ohio Department of Health Statewide Immunization Information System included demographics, transplant-related data, immunization administration history, and quantitative/qualitative values for titer/serology. The primary objective of vaccination adherence rate was defined as the aggregate of patients who had completed the vaccine series, had positive titer/serology data, or were ineligible to receive the vaccine due to age or administration restrictions. Data are descriptive in nature and reported as number (percent) or median (interquartile range), as appropriate.Results64 pediatric SOT recipients met inclusion criteria. Median age was 7.9 (2.1, 15.8) years. Majority of patients were American (73%) and male (63%). Most common organ was heart (41%), followed by liver (25%), kidney (21%), and intestine/multi-visceral (13%). Sixty-three (98%) patients underwent ID pre-txp evaluation. CCCH adherence rates were highest for hepatitis B at 92%, followed by PCV13 and PPSV23 at 84%, and influenza at 72%. Thirty-two (50%) patients were indicated to receive the hepatitis A vaccine and the respective adherence rate was 91%. Vaccination adherence by SOT team is described in Figure 1.ConclusionCCCH pre-txp vaccination adherence rates are higher than previously reported. Opportunities for improvement include influenza vaccination adherence across all SOT teams and PCV13/PPSV23 vaccination adherence in intestine/multi-visceral transplant patients. Figure 1: CCCH SOT team vaccination adherence rates.Disclosures All authors: No reported disclosures.