Pediatric Solid Organ Transplant Research Articles

#42 A Retrospective Study of Valganciclovir Discontinuation Due to Toxicity or Intolerance in Pediatric Solid Organ Transplant Patients

Abstract Background Cytomegalovirus (CMV) prevention strategies in pediatric solid organ transplantation (SOT) recipients include universal prophylaxis or pre-emptive therapy with valganciclovir (VGCV) based on CMV risk stratification. However, VGCV is associated with myelosuppresion and nephrotoxicity, which may result in premature termination or dose modifications of VGCV and/or discontinuation of Pneumocystis jirovecii pneumonia (PJP) prophylaxis with trimethoprim-sulfamethoxazole (TMP-SMX), which is also myelosupressive. There are no currently approved alternatives for CMV prevention in pediatric SOT patients. Thus, the specific aims of this study were to determine the frequency with which SOT recipients receiving VGCV develop neutropenia or lymphopenia, how often VGCV or TMP-SMX are discontinued or have a dose reduction, and whether changes in CMV prophylaxis are associated with increased rates of CMV DNAemia or disease. Method A retrospective, observational study of pediatric SOT recipients who were < 20 years old and who initiated VGCV prophylaxis, with the intent to receive at least 3 months of therapy, was conducted at 8 U.S. centers between January 2016 and December 2019. Each site abstracted demographic and clinical data for 1 year post-transplantation into a central REDCap electronic database hosted at St Jude. Patients with complete information as of December 2021 (n= 557) were included in this preliminary analysis. Results The cohort included 201 renal (36%), 101 cardiac (18%), 202 liver (36%), 34 lung (6%), 10 multivisceral (2%), 2 intestinal and 6 other SOT recipients. Median age at transplantation was 9.5 [IQR: 2.7- 14] years; 52% were male. VGCV was prematurely discontinued in 31 and the dose was adjusted in 168 resulting in changes in 199 (36%) recipients. TMP-SMX was discontinued prematurely in 61 and changed to an alternative therapy in 77 patients resulting in changes in 131 (24%) recipients. Seven patients discontinued both medications. No breakthrough cases of Pneumocystis pneumonia were documented. There were 119 (21%) patients with at least one episode of CMV DNAemia in the first year post-transplant, 54 (45%) of these occurred in patients who had changes to their VGCV prophylaxis. Conclusion Preliminary analysis of this large pediatric cohort suggests that CMV prophylaxis with VGCV is difficult to maintain and requires frequent dose adjustments and/or discontinuation of either VGCV and/or TMP-SMX for PJP prophylaxis. Despite alterations in PJP prophylaxis, no breakthrough infections were documented. These findings highlight the need to study the safety and efficacy of alternative prophylactic options for CMV in pediatric SOT recipients.

#46 A Multicenter Study Exploring the Epidemiology and Outcomes of COVID-19 Among Pediatric Hematopoietic Cell Transplant, Cellular Therapy and Solid Organ Transplant Recipients: Preliminary Results from the Pediatric COVID-19 U.S. Registry.

BackgroundWhile most pediatric patients with COVID-19 experience mild disease, children with a history of hematopoietic cell transplant or cellular therapy (HCT/CT) or solid organ transplant (SOT) may be at increased risk for severe disease. Despite this, there is a dearth of data from multicenter studies examining COVID-19 outcomes among pediatric HCT/CT and SOT recipients. We present descriptive results from the Pediatric COVID-19 U.S. registry to characterize COVID-19 illness among pediatric HCT/CT and SOT recipients across the United States.MethodDemographic, medical history, and COVID-19 related data were extracted from HCT/CT and SOT recipient medical records and submitted to the Pediatric COVID-19 U.S. Registry, a passive surveillance registry of pediatric patients less than 21 years old diagnosed with COVID-19 between March 2020 and April 2021. Participating US centers (n=170) submitted de-identified information for inpatients and outpatients at 7- and 28-days post COVID-19 diagnosis via a publicly available REDCap electronic survey. Data were summarized descriptively to characterize COVID-19 hospitalizations among HCT/CT and SOT recipients.ResultsOf the 13,140 registry COVID-19 cases, a total of 202 (1.5%) were patients with history of HCT/CT (n=58) or SOT (n=144). Median age at COVID-19 diagnosis among HCT/CT was 9.5 years (range 0.66 to 18) and SOT was 13.5 years (range 1 to 20). Over half of HCT (64%) and SOT (53.8%) patients were White/Caucasian and 26% of HCT and 39% of SOT here Hispanic/Latino. Hospitalizations among HCT/CT and SOT accounted for approximately 12% of all hospitalizations reported to the registry (n = 1683). Almost half of the reported HCT/CT (48%) and SOT (44%) cases were hospitalized. In those hospitalized, 11 (19%) HCT and 18 (12.5%) SOT cases required ICU admission. Half (50%) of HCT hospitalized cases received oxygen support and 3 (11%) required mechanical ventilation while only 2 (0.6%) SOT cases received oxygen support, and none required mechanical ventilation. The majority of HCT/CT cases (64%) were hospitalized between Days 100 and 365 post-transplant. Approximately half (48%) of the HCT cases had received an allogenic HCT. Myeloablative conditioning was the most common regimen reported (48%) among hospitalized HCT cases. Approximately half of SOT hospitalized cases had received a kidney transplant (48%) followed by liver (30%) and heart (19%). Of the 63 hospitalized SOT cases, the majority (87%) were receiving tacrolimus at COVID-19 diagnosis. One SOT death related to COVID-19 was reported, while no related deaths were reported in the HCT/CT group.ConclusionAlthough HCT/CT and SOT cases were low in comparison to all cases submitted to the registry, almost half of these cases required hospitalization. Only one COVID-19 related death was reported (SOT group); however, up to 20% of cases received ICU care. This data may aid clinicians developing future prospective studies examining COVID-19 risk mitigation and effective treatment strategies among this increased-risk population.

Incidence of and Risk Factors for Keratinocyte Carcinoma After Pediatric Solid Organ Transplant

This cohort study identifies the risk factors for and the incidence of keratinocyte carcinoma among patients who underwent solid organ transplant during childhood compared with the general population in Ontario, Canada.

Long-term respiratory outcomes following solid organ transplantation in children: A retrospective cohort study.

Solid-organ transplantation (SOT) has become commonly used in children and is associated with excellent survival rates into adulthood. Data regarding long-term respiratory outcomes following pediatric transplantation are lacking. We aimed to describe the prevalence and nature of respiratory pathology following pediatric heart, kidney, and liver transplant, and identify potential risk factors for respiratory complications. Retrospective review involving all children under active follow-up at the provincial transplant service in British Columbia, Canada, following SOT. Of 118 children, 33% experienced respiratory complications, increasing to 54% in heart transplant recipients. Chronic or recurrent cough with persistent chest x-ray changes was the most common clinical picture, and most infections were with nonopportunistic organisms typically found in otherwise healthy children. A history of respiratory illness before transplant was significantly associated with risk of posttransplant respiratory complications. Eight percentage8% were diagnosed with bronchiectasis, which was more common in recipients of heart and kidney transplant. Bronchiectasis was associated with recurrent hospital admissions with lower respiratory tract infections, treatment of acute rejection episodes, and treatment with sirolimus. Respiratory morbidity is common after pediatric SOT, and bronchiectasis rates were disproportionately high in this patient group. We hypothesize that this relates to recurrent infections resulting from iatrogenic immunosuppression. Direct pulmonary toxicity from immunosuppression drugs may also be contributory. A high index of suspicion for respiratory complications is needed following childhood SOT, particularly in those with a history of respiratory disease before transplant, experiencing recurrent or severe respiratory tract infections, or exposed to intensified immunosuppression.

Pediatric transplantation during the COVID-19 pandemic.

Children infected by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) seem to have a better prognosis than adults. Nevertheless, pediatric solid organ transplantation (SOT) has been significantly affected by the unprecedented coronavirus disease 2019 (COVID-19) pandemic during the pre-, peri-, and post-transplant period. Undoubtedly, immunosuppression constitutes a real challenge for transplant clinicians as increased immunosuppression may prolong disease recovery, while its decrease can contribute to more severe symptoms. To date, most pediatric SOT recipients infected by SARS-CoV-2 experience mild disease with only scarce reports of life-threatening complications. As a consequence, after an initial drop during the early phase of the pandemic, pediatric SOTs are now performed with the same frequency as during the pre-pandemic period. This review summarizes the currently available evidence regarding pediatric SOT during the COVID-19 pandemic.

Anesthetic considerations for pediatric abdominal solid organ transplantation

While many pediatric patients undergo abdominal solid organ transplants every year worldwide, each is unique due to varying age, size, and comorbidities; thus, they require a careful anesthesia plan to undergo surgery safely. This article reviews the anesthetic considerations and management of patients undergoing liver and kidney transplantation. Preoperative, intraoperative, and post-operative management are discussed, including induction, access, monitoring, and maintenance. Blood transfusion is also addressed.

The impact of COVID-19 on the pediatric solid organ transplant population

The coronavirus disease 2019 (COVID-19) pandemic caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has significantly impacted all aspects of healthcare including solid organ transplantation. In this review, we discuss the specific impact of COVID-19 on the pediatric solid organ transplant population including access to grafts for pediatric transplant candidates as well as COVID-19 disease manifestations in pediatric transplant recipients. We address the current knowledge of prevention and management of COVID-19 in pediatric transplant recipients and provide additional information regarding social distancing, infection prevention and return to school.

Transitional care models in adolescent kidney transplant recipients-a systematic review.

Adolescence is a time of significant change for patients, guardians and clinicians. The paediatrician must ensure patients develop the necessary skills and knowledge required to transition and to function as an independent entity, with autonomy over their own care. The transfer from paediatric to adult care carries an increased risk of graft-related complications attributable to a multitude of reasons, particularly non-adherence to immunosuppressive medicines and poor attendance at scheduled appointments. This systematic review was conducted to ascertain the transitional care models available to clinicians caring for kidney transplant recipients and to compare the approach in each respective case. A systematic review was performed, in a methodology outlined by the PRISMA guidelines. OVID MEDLINE and EMBASE databases were searched for studies that outlined valid, replicable models pertaining to transitional care of paediatric kidney transplant recipients between 1946 and Quarter 3 of 2021. The reference lists of selected articles were also perused for further eligible studies and experts in the field were consulted for further eligible articles. Two investigators assessed all studies for eligibility and independently performed data extraction. Any discrepancies were settled by consensus. A total of 1121 abstracts were identified, which was reduced to 1029 upon removal of duplicates. A total of 51 articles were deemed appropriate for full-text review and critical appraisal. A total of 12 articles that described models for transition pertaining to kidney transplant patients were included in qualitative synthesis. Every paper utilized a different transition model. All but one model included a physician and nurse at minimum in the transition process. The involvement of adult nephrologists, medical social work, psychology and psychiatry was variable. The mean age for the initiation of transition was 13.4 years (range: 10-17.5 years). The mean age at transfer to adult services was 18.3 years (range: 16-20.5 years). Despite the well-established need for good transitional care for paediatric solid-organ transplant recipients, models tailored specifically for kidney transplant recipients are lacking. Further research and validation studies are required to ascertain the best method of providing effective transitional care to these patients. Transitional care should become a standardized process for adolescents and young adults with kidney transplants.

Our Pediatric Liver and Kidney Transplant Activities in 2021.

In children with end-stage renal disease, chronic liver failure, or acute liver failure, liver transplant and kidney transplant are the most effective modalities for better clinical outcomes compared with other therapies. However, children are particularly susceptible to surgical complications, so pediatric solid-organ transplants should be reserved for centers with substantial experience and multidisciplinary expertise. Here, we assessed liver and kidney transplants performed at our center in 2021. From November 3, 1975, to December 31, 2021, we performed 701 liver transplants and 3290 kidney transplants. From January 1, 2021, to December 31, 2021, we performed 21 liver transplants (19 in children) and 114 kidney transplants (12 in children). We recorded age, sex, body mass index, comorbidities, etiologies, laboratory values, and clinical outcomes. For the year 2021, we performed 19 pediatric liver transplants and 12 pediatric kidney transplants. Mean age of liver recipients was 3.4 years, and 8 were male patients. The most common etiology was biliary atresia (n = 7). All liver grafts were from living related donors who were first-degree (n = 16) or second- degree (n = 3) relatives of the recipients. Mean hospital stay was 17.6 days. All but 2 liver transplant recipients were discharged successfully (2 died from sepsis in the early postoperative period). Mean age of kidney transplant recipients was 14.1 years, and 4 were male patients. The most common etiology was vesicoureteral reflux (n = 3). One kidney graft was from a deceased donor, with the rest from living related donors who were first-degree relatives of the recipients (n = 11; mother for 8 recipients and father for 3 recipients). Mean hospital stay was 4.3 days. All kidney transplant recipients were discharged successfully. Solid-organ transplants for young children are often complex but can be performed successfully at experienced transplant centers.

Quadratus lumborum blocks for abdominal transplant surgeries at UPMC Children's Hospital of Pittsburgh-A five year experience.

Adequate perioperative analgesia for pediatric abdominal transplant surgery is essential for patient recovery. However, the risks of commonly used medications such as hepatotoxicity, nephrotoxicity, bleeding concerns, and poor graft results with opioids limit pain management in this population. Thoracic epidural, continuous erector spinae plane, and type-1 quadratus lumborum blocks (QLBs) have been described and utilized in the adult population in this setting. The safety and benefits of regional anesthetic techniques in pediatrics have been widely documented for different types of procedures except pediatric abdominal transplantation, where data remains scarce. Our primary goal was to determine if QLBs provided adequate perioperative analgesia when part of a multimodal approach. Secondary objectives were to examine complications and effects on the intensive care unit (ICU) and hospital stay. We performed a retrospective, observational study of pediatric patients who underwent abdominal transplant surgeries at the University of Pittsburgh Medical Center Children's Hospital of Pittsburgh from January 2015 to July 2021 and received a single injection QLB for pain control. Data collected included: demographics, nerve block characteristics, perioperative opioid consumption, use of non-opioid analgesia, daily pain scores, and hospital and ICU stay. Forty-two patients met the inclusion criteria for our study. Our results suggest that QLBs decrease opioid consumption, facilitate early extubation, prevent reintubation in the ICU, and reduce ICU and hospital stay. QLB is feasible and can be used as a multimodal approach for postoperative pain control in pediatric solid organ transplantation.

Presentation and outcomes of post-transplant lymphoproliferative disorder at a single institution pediatric transplant center.

This study aimed to characterize features present at the time of diagnosis and describe outcomes in patients with post-transplant lymphoproliferative disorder (PTLD) following pediatric solid organ transplantation. We performed a retrospective review of solid organ transplant patients who developed pathologically confirmed PTLD at our center from 2006 to 2016. Of 594 patients included in this study, 41(6.9%) were diagnosed with PTLD. Median age at transplant was 5.6(IQR 1.7-16.1) years. Proportion of PTLD cases by organ transplanted and median time (IQR) to disease onset were: heart 11/144(7.6%) at 13.6(8.5-55.6) months, lung 7/52(13.5%) at 9.1(4.9-35) months, kidney 8/255(3.1%) at 39.5(13.9-57.1) months, liver 12/125(9.6%) at 7.7(5.5-22) months, intestine 0/4(0%), and multi-visceral 3/14(21.4%) at 5.4(5.4-5.6) months. No significant correlation was seen between recipient EBV status at transplant and timing of development of PTLD. There were six early lesions, 15 polymorphic, 19monomorphic, and one uncharacterizable PTLD. Following immunosuppression reduction, 30 patients received rituximab, and 14 required chemotherapy. At median 25(IQR 12-53) months follow-up from the onset of PTLD, eight patients died secondary to transplant related complications, three are alive with active disease, and 30have no evidence of disease. PTLD is a significant complication following pediatric solid organ transplantation. EBV levels in conjunction with symptomatic presentation following transplant may assist in detection of PTLD. Most patients can achieve long-term disease-free survival through immunosuppression reduction, anti-CD20 treatment, and chemotherapy in refractory cases.

Paediatric living-donor liver and kidney transplantation during COVID-19

Dear Editor, The coronavirus disease 2019 (COVID-19) pandemic has impacted global healthcare including paediatric solid organ transplantation (SOT). We report our experience of resuming paediatric living-donor SOT during COVID-19, which took into account safety considerations for living donors, paediatric recipients and the transplant healthcare team. The US Centers for Disease Control and Prevention has categorised

The case against COVID-19 vaccine mandates in pediatric solid organ transplantation.

BackgroundThe American Society of Transplantation in conjunction with the International Society for Heart and Lung Transplantation released a joint statement on August 13, 2021 in which they strongly recommend that solid organ transplant (SOT) recipients and their eligible household members and close contacts be vaccinated against SARS‐CoV‐2 with an approved COVID‐19 vaccine. Some SOT programs have gone further and will refuse to list or transplant candidates unless the candidate and their household are vaccinated against SARS‐CoV‐2.MethodsTwo general pediatrician‐ethicists use current best evidence and moral theory to argue why it is unethical to mandate COVID‐19 vaccination for pediatric SOT candidates, their primary support person, and their households.ResultsPediatric vaccine mandates are most justifiable when they prevent the harm of a serious vaccine preventable disease (VPD) in children in settings where transmission is highly likely and there are no alternatives that are effective in preventing transmission that intrude less on individual freedom. An additional justification for a vaccine mandate in the SOT context is stewardship of a scarce resource if there is significant risk of graft loss from the VPD to an unvaccinated SOT candidate or recipient. Current evidence does not support fulfillment of these criteria in pediatric solid organ transplantation.ConclusionsMaking SOT listing contingent on COVID‐19 vaccination is problematic. Though there is some risk of harm to a pediatric SOT candidate in remaining unvaccinated, the risk of harm of not being listed and transplanted is greater and overriding.

Updates From the NASPGHAN/SPLIT SARS-CoV2 International Registry.

Reply: We acknowledge the authors of “SARS-CoV-2 in pediatric liver transplant recipients: the European experience” response to our article reporting the NASPGHAN/SPLIT SARS-CoV2 registry experience (1). In contrast, they note that liver transplant (LT) recipients had higher rates of hospitalization, including intensive care unit (ICU) admission, than patients with chronic liver disease (LD). The NASPGHAN/SPLIT SARS-CoV2 international registry has increased to 180 LT recipients and 76 patients with LD (Table 1). In this expanded cohort, LT recipients were still less likely to require hospitalization (odds ratio [OR] = 0.32, 95% confidence interval [CI]: 0.17–0.59, P < 0.0001) or ICU level care (OR = 0.05, 95% CI: 0.010.17, P < 0.001) compared with LD patients. No LT recipients required mechanical ventilation or died of SARS-CoV2. Nine patients with LD required mechanical ventilation, and three patients with LD died. Differences between registry outcomes may be partially explained by the higher proportion of patients with obesity and NAFLD with LD in our cohort. Obesity is associated with worse outcomes in children with SARS-CoV2 infection (1,2–5). Buescher et al additionally suggest a role of combined immunosuppression leading to increased hospitalization in LT recipients. In our larger LT cohort, the degree of immunosuppression was not associated with higher odds of hospitalization (OR = 1.6, 95% CI: 0.69–3.8, P = 0.20). TABLE 1 - Baseline characteristics and clinical data for patients with disease of the native liver and liver transplant recipients with positive test for the severe acute respiratory syndrome coronavirus 2 Disease of the native liver (N = 76) Liver transplant recipient (N = 180) P value Baseline characteristics Age (y), median (IQR) 9.5 (4–16) 11.5 (5–17) 0.05 Male gender (%) 45 (59) 93 (52) 0.2 Primary liver condition (%) <0.001 NAFLD 13 (17) 0 Biliary atresia 18 (24) 85 (47) Acute liver failure 4 (5) 16 (9) Autoimmune hepatitis 13 (17) 7 (4) Metabolic 6 (8) 23 (13) Malignancy 3 (4) 18 (10) Other cholestatic liver disease 15 (20) 21 (12) Other 4 (5) 10 (6) Comorbid conditions (%) None 20 (26) 97 (54) Overweight/obesity 18 (24) 13 (7) <0.001 Cardiac 10 (13) 22 (12) 0.8 Gastrointestinal 11 (14) 10 (6) 0.03 Pulmonary 6 (8) 11 (6) 0.6 Renal 2 (3) 16 (9) 0.07 Endocrine 4 (5) 5 (3) 0.4 Other autoimmune conditions 2 (3) 5 (3) Time since LT (y), median (IQR) – 4.5 (2–11) Clinical data Presenting symptoms (%) Fever 27 (36) 49 (27) Respiratory symptoms 36 (47) 65 (36) Constitutional symptoms 11 (14) 23 (13) Gastrointestinal symptoms 18 (24) 29 (16) Asymptomatic 16 (21) 63 (35) Highest level of care (%) Outpatient 28 (37) 147 (82) <0.001 Hospital floor 29 (38) 30 (16) <0.001 ICU 19 (25) 3 (12) <0.001 Highest respiratory support (%) <0.001 None 60 (79) 177 (98) Nasal cannula/CPAP/BiPAP 7 (9) 3 (2) Mechanical ventilation 6 (8) 0 High frequency oscillatory ventilation 3 (4) 0 Final clinical outcome (%) 0.02 Death 3 (4) 0 Recovery 67 (88) 175 (97) Still active in clinical course/pending 7 (8) 5 (3) ICU = intensive care unit; IQR = interquartile range; LT = liver transplant; N = number; NAFLD = non-alcoholic fatty liver disease. We agree with Buescher et al regarding the utility of collaborative registry studies to inform the care of pediatric LT recipients and children with LD. Our registry continues to collect data (https://bit.ly/NASPGHAN_SPLIT_COVIDregistry). Ongoing submissions remain critical as we continue to explore variants, breakthrough infections, and antibody response to SARS-CoV2 vaccination in pediatric solid organ transplant recipients (6,7).

Update on COVID-19 vaccination in pediatric solid organ transplant recipients.

COVID-19 vaccination has been successful in decreasing rates of SARS-CoV-2 infection in areas with high vaccine uptake. Cases of breakthrough SARS-CoV-2 infection remain infrequent among immunocompetent vaccine recipients who are protected from severe COVID-19. Robust data demonstrate the safety, immunogenicity, and effectiveness of several COVID-19 vaccine formulations. Importantly, Pfizer-BioNTech BNT162b2mRNA COVID-19 vaccine studies have now included children as young as 5years of age with safety, immunogenicity, and effectiveness data publicly available. In the United States, emergency use authorization by the Federal Drug Administration and approval from the Centers for Disease Control/Advisory Committee on Immunization Practices have been provided for the 5- to 11-year-old age group. Members of the International Pediatric Transplant Association (IPTA) provide an updated review of current COVID-19 vaccine data with focus on pediatric solid organ transplant (SOT)-specific issues. This review provides an overview of current COVID-19 immunogenicity, safety, and efficacy data from key studies, with focus on data of importance to pediatric SOT recipients. Continued paucity of data in the setting of pediatric transplantation remains a challenge. Further studies of COVID-19 vaccination in pediatric SOT recipients are needed to better understand post-vaccine COVID-19T-cell and antibody kinetics and determine the optimal vaccine schedule. Increased COVID-19 vaccine acceptability, uptake, and worldwide availability are needed to limit the risk that COVID-19 poses to pediatric solid organ transplant recipients.

Long-Term Varicella Zoster Virus Immunity in Paediatric Liver Transplant Patients Can Be Achieved by Booster Vaccinations-A Single-Centre, Retrospective, Observational Analysis.

Varicella is one of the most common vaccine-preventable infections after paediatric solid organ transplantation; thus, vaccination offers simple and cheap protection. However, children with liver disease often progress to liver transplantation (LT) before they reach the recommended vaccination age. As a live vaccine, varicella zoster virus (VZV) vaccination after transplantation is controversial; however, many case series demonstrate that vaccination may be safe and effective in paediatric liver transplant recipients. Only limited data exists describing long-term vaccination response in such immunocompromised patients. We investigated retrospectively vaccination response in paediatric patients before and after transplantation and describe long-term immunity over ten years, including the influence of booster-vaccinations. In this retrospective, single-centre study, 458 LT recipients were analysed between September 2004 and June 2021. Of these, 53 were re-transplantations. Patients with no available vaccination records and with a history of post-transplant lymphoproliferative disease, after hematopoietic stem cell transplantation and clinical chickenpox were excluded from this analysis (n = 198). In total, data on 207 children with a median annual follow-up of 6.2 years was available: 95 patients (45.9%) were unvaccinated prior to LT. Compared to healthy children, the response to vaccination, measured by seroconversion, is weaker in children with liver disease: almost 70% after one vaccination and 93% after two vaccinations. One year after transplantation, the mean titres and the number of children with protective antibody levels (VZV IgG ≥ 50 IU/L) decreased from 77.5% to 41.3%. Neither diagnosis, gender, nor age were predictors of vaccination response. Booster-vaccination was recommended for children after seroreversion using annual titre measurements and led to a significant increase in mean titre and number of protected children. Response to vaccination shows no difference from monotherapy with a calcineurin inhibitor to intensified immunosuppression by adding prednisolone or mycophenolate mofetil. Children with liver disease show weaker seroconversion rates to VZV vaccination compared to healthy children. Therefore, VZV-naïve children should receive basic immunization with two vaccine doses as well as those vaccinated only once before transplantation. An average of 2–3 vaccine doses are required in order to achieve a long-term seroconversion and protective antibody levels in 95% of children.

Vaccination in pediatric solid organ transplant: A primer for the immunizing clinician.

Pediatric solid organ transplant (SOT) recipients are at a uniquely elevated risk for vaccine preventable illness (VPI) secondary to a multitude of factors including incomplete immunization at the time of transplant, inadequate response to vaccines with immunosuppression, waning antibody titers observed post-SOT, and uncertainty among providers on the correct immunization schedule to utilize post-SOT. Multiple guidelines are in existence from the Infectious Diseases Society of America and the American Society of Transplantation, which require use in adjunct with additional published references. We summarize the present state of SOT vaccine recommendations from relevant resources in tandem with the Centers for Disease Control and Prevention Advisory Committee on Immunization Practices guidance utilizing both routine and rapid catch-up schedules. The purpose of this all-inclusive review is to provide improved clarity on the most optimal pre- and post-transplant vaccine management within a one-stop-shop for the immunizing clinician.

A Smartphone App to Increase Immunizations in the Pediatric Solid Organ Transplant Population: Development and Initial Usability Study

BackgroundVaccine-preventable infections result in significant morbidity, mortality, and costs in pediatric transplant recipients. However, at the time of transplant, less than 20% of children are up-to-date for age-appropriate immunizations that could prevent these diseases. Smartphone apps have the potential to increase immunization rates through their ability to provide vaccine education, send vaccine reminders, and facilitate communication between parents and a multidisciplinary medical group.ObjectiveThe aim of this study was to describe the development of a smartphone app, Immunize PediatricTransplant, to promote pretransplant immunization and to report on app functionality and usability when applied to the target population.MethodsWe used a mixed methods study design guided by the Mobile Health Agile Development and Evaluation Lifecycle. We first completed a formative research including semistructured interviews with transplant stakeholders (12 primary care physicians, 40 parents or guardians of transplant recipients, 11 transplant nurse coordinators, and 19 transplant subspecialists) to explore the acceptability of an immunization app to be used in the pretransplant period. Based on these findings, CANImmunize Inc developed the Immunize PediatricTransplant app. We next held 2 focus group discussions with 5-6 transplant stakeholders/group (n=11; 5 parents of transplant recipients, 2 primary care physicians, 2 transplant nurse coordinators, and 2 transplant subspecialists) to receive feedback on the app. After the app modifications were made, alpha testing was conducted on the functional prototype. We then implemented beta testing with 12 stakeholders (6 parents of transplant recipients, 2 primary care doctors, 2 transplant nurse coordinators, and 2 transplant subspecialists) to refine the app through an iterative process. Finally, the stakeholders completed the user version of the Mobile Application Rating Scale (uMARS) to assess the functionality and quality of the app.ResultsA new Android- and Apple-compatible app, Immunize PediatricTransplant, was developed to improve immunization delivery in the pretransplant period. The app contains information about vaccine use in the pretransplant period, houses a complete immunization record for each child, includes a communication tool for parents and care providers, and sends automated reminders to parents and care providers when immunizations are due. During usability testing, the stakeholders were able to enter a mock vaccine record containing 16 vaccines in an average of 8.1 minutes (SD 1.8) with 87% accuracy. The stakeholders rated engagement, functionality, aesthetics, and information quality of the app as 4.2/5, 4.5/5, 4.6/5, and 4.8/5, respectively. All participants reported that they would recommend this app to families and care teams with a child awaiting solid organ transplant.ConclusionsThrough a systematic, user-centered, agile, iterative approach, the Immunize PediatricTransplant app was developed to improve immunization delivery in the pretransplant period. The app tested well with end users. Further testing and agile development among patients awaiting transplant are needed to understand real-world acceptability and effectiveness in improving immunization rates in children awaiting transplant.

CMV infection and management among pediatric solid organ transplant recipients.

Cytomegalovirus (CMV) is an important cause of morbidity and mortality in pediatric solid organ transplant (SOT) recipients. However, the impact of asymptomatic CMV infections (ie, DNAemia) on clinical outcomes is not well established. We performed a retrospective cohort study of children undergoing first SOT at our institution from January 2012 to June 2018. We evaluated the epidemiology of CMV infections and performed multivariable Cox regression to assess the association between CMV DNAemia without disease or CMV disease (syndrome or end-organ disease) on negative outcomes (death, re-transplantation, or moderate/severe rejection) within the first year after SOT. Among 271 individuals, 43 (15.9%) developed ≥1 CMV infection during the first year after SOT. There were 56 unique CMV infections including 14 episodes of CMV disease. In 167 patients offered CMV prophylaxis, only 8 (4.8%) developed their first CMV DNAemia episode while on prophylaxis 32 developed CMV DNAemia after prophylaxis completion; only 1 episode of CMV disease occurred while on antiviral prophylaxis. When accounting for receipt of ATG, oral steroids, and number of immunosuppressives on a given day, CMV disease was more strongly associated with negative outcomes (Hazard Ratio (HR): 3.28, 95% CI: 0.73-14.64; p=.12) than CMV DNAemia without disease (HR 1.42, 95% CI: 0.19- 10.79; p=.74), although not to a statistically significant degree. Most CMV infections occurred after completion of antiviral prophylaxis. CMV disease was more strongly associated with negative outcomes than asymptomatic CMV DNAemia and should be the focus of CMV prevention practices.

Epidemiology and long-term outcomes of cytomegalovirus DNAemia and disease in pediatric solid organ transplant recipients

Despite prevention strategies, cytomegalovirus (CMV) remains a common infection in pediatric solid organ transplant recipients (SOTR). We sought to determine the frequency, associations with, and long-term outcomes of CMV DNAemia in pediatric SOTR. We performed a single-center retrospective cohort study, including 687 first time SOTR ≤21years receiving universal prophylaxis from 2011 to 2018. Overall, 159 (23%) developed CMV DNAemia, the majority occurring after completing primary prophylaxis. CMV disease occurred in 33 (5%) SOTR, 25 (4%) with CMV syndrome and 10 (1%) with proven/probable tissue-invasive disease. CMV contributed to the death of three (0.4%) patients (all lung). High-risk (OR 6.86 [95% CI, 3.6-12.9]) and intermediate-risk (4.36 [2.3-8.2]) CMV status and lung transplantation (4.63 [2.33-9.2]) were associated with DNAemia on multivariable analysis. DNAemia was associated with rejection in liver transplant recipients (p<.01). DNAemia was not associated with an increase in graft failure, all-cause mortality, or other organ-specific poor outcomes. We report one of the lowest rates of CMV disease after SOTR, showing that universal prophylaxis is effective and should be continued. However, we observed CMV morbidity and mortality in a subset of patients, highlighting the need for research on optimal prevention strategies. This study was IRB approved.