Pediatric Transplant Program Research Articles

Comparison of alloimmune risk stratification method for kidney transplants: Correlation with outcomes from a single center pediatric transplant program

Comparison of alloimmune risk stratification method for kidney transplants: Correlation with outcomes from a single center pediatric transplant program

The role of donor type and pre-transplant immunosuppression on outcomes of hematopoietic stem cell transplantation in children and young adults with severe aplastic anemia.

The goal of this study was to assess the effect of donor type and pre-transplant immunotherapy (IST) on outcomes of hematopoietic stem cell transplantation (HSCT) for children and young adults with severe aplastic anemia (SAA). This retrospective, multi-center study included 52 SAA patients, treated in 5 pediatric transplant programs in Florida, who received HSCT between 2010 and 2020 as the first- or second-line treatment. The median age at HSCT for all 52 patients was 15 years (range 1-25). The 3-year overall survival (OS) by donor type were as follows: 95% [95% CI 85.4-99] for matched related donors (MRD) (N = 24), 84% [95% CI 63.5-99] for haploidentical (N = 13), and 71% [95% CI 36-99] for matched unrelated donors (MUD) (N = 7). The 3-year OS was 81% [95% CI 69.7-99] for all patients, 90.5% [95% CI 79.5-99] for non-IST patients (N = 27), and 70% [95% CI 51-99] for IST patients (N = 24) (log-rank p = .04). Survival of haploidentical HSCT (haplo-HSCT) recipients with post-transplant cyclophosphamide (PTCy) (N = 13) was excellent for both groups: 100% for non-IST patients (N = 3) and 80% for IST patients (N = 10). The 3-year OS for patients with previous IST by donor type in groups where >5 patients were available was 78.8% [95% CI 52.3-99] for haplo-HSCT (N = 10) and 66.7% [95% CI 28.7-99] for MUD (N = 6). Although it appears that patients receiving HSCT ≥6 months after the start of IST had worse survival, the number of patients in each category was small and log-rank was not significant(p = .65). Patients receiving MUD and haplo-HSCT with PTCy had similar outcomes, suggesting that haplo-HSCT with PTCy could be included in randomized trials of upfront IST versus alternative donor HSCT.

Variability in pediatric and neonatal organ offering, acceptance and utilization: a survey of Canadian pediatric transplant programs and organ donation organizations.

Solid organ transplantation in children is a lifesaving therapy, however, pediatric organ donation rates remain suboptimal. We conducted a cross-sectional survey of Canadian organ donation organizations (ODOs) and pediatric transplant programs (TPs), aiming to describe policies and practices for pediatric organ allocation, acceptance, and utilization in Canada. Response rates were 82% and 83% respectively for ODOs and transplant programs comprising 7 kidney, 3 heart, 2 lung, 2 liver and 1 intestine programs. All 9 ODOs reported offering pediatric organs following death by neurological criteria (DNC), while 8 reported offering organs following death by circulatory criteria (DCC) for some organs. Variability was found across ODOs and TPs. There was little agreement on both absolute and organ-specific donor exclusion criteria between ODOs. There was further disagreement in organ specific acceptance criteria between ODOs and TPs and between TPs themselves. Notably, despite the development of pediatric donation after DCC guidelines, organs from DCC donors are excluded by many ODOs and TPs. Further variability in pediatric specific training, policies, and allocation guidelines are also documented. Significant areas for improvement in standardization in organ acceptance, offering, and allocation in pediatric donation and transplantation across Canada were identified.

Pediatric Liver and Transplant Surgery: Results of an International Survey and Expert Consensus Recommendations.

Pediatric liver surgery is a complex and challenging procedure and can be associated with major complications, including mortality. Best practices are not established. The aims of this study were to evaluate surgeons' individual and institutional practices in pediatric liver surgery and make recommendations applicable to the management of children who require liver surgery. A web-based survey was developed, focusing on the surgical management of children with liver conditions. It was distributed to 34 pediatric surgery faculty members of the Biliary Atresia and Related Disorders (BARD) consortium and 28 centers of the European Reference Network-Rare Liver. Using the Delphi method, a series of questions was then created to develop ideas about potential future developments in pediatric liver surgery. The overall survey response rate was 70.6% (24/34), while the response rate for the Delphi questionnaire was 26.5% (9/34). In centers performing pediatric liver surgery, most pediatric subspecialties were present, although pediatric oncology was the least present (79.2%). Nearly all participants surveyed agreed that basic and advanced imaging modalities (including ERCP) should be available in those centers. Most pediatric liver surgeries were performed by pediatric surgeons (69.6%). A majority of participants agreed that centers treating pediatric liver tumors should include a pediatric transplant program (86%) able to perform technical variant grafts and living donor liver transplantation. Fifty-six percent of responders believe pediatric liver transplantation should be performed by specialized pediatric surgeons. Pediatric liver surgery should be performed by specialized pediatric surgeons and should be centralized in regional centers of excellence where all pediatric subspecialists are present. Pediatric hepatobiliary and transplant training needs to be better promoted amongst pediatric surgery fellows to increase this subspecialized workforce.

Opening a Crack in the Door: An Interview with Haydar Frangoul

Opening a Crack in the Door: An Interview with Haydar Frangoul

Exploring the Ethical Considerations of Direct Contact in Pediatric Organ Transplantation: A Qualitative Study

Background Nonanonymized direct contact between organ recipients and donor families is a topic of international interest in the adult context. However, there is limited discussion about whether direct contact should be extended to pediatric settings due to clinician and researcher concerns of the potential harms to pediatric patients. Methods We interviewed pediatric organ recipients, their families, and donorfamilies in British Columbia, Canada, to determine their views on direct contact. Interviews were conducted in two stages, with those who were further removed from the transplant process informing the approach to interviews with those who more recently went throughthe transplant process. Results Twenty-nine individuals participated in twenty in-depth interviews. The study included participants from three major organ systems: kidney, heart, and liver. Only five participants expressed that direct contact might cause harm or discomfort, while twenty-three indicated they saw significant potential for benefits. Nearly half focused on the harms to others rather than themselves, and nearly two-thirds focused on the benefits for others rather than themselves. Conclusion There appears to be a community desire for direct contact in pediatric organ transplant programs among those living in British Columbia, Canada. These results suggest a need to revisit the medical community’s assumptions around protection and paternalism in our practice as clinicians and researchers.

1096. Riding the Waves: Infection by SARS-CoV-2 Variants in Solid Organ Transplant Recipients at Texas Children’s Hospital

Abstract Background Texas Children’s Hospital is the largest pediatric solid organ transplant (SOT) program in the US, performing heart, kidney, liver, and lung transplants. Limited data exist about SARS-CoV-2 infection (COVID-19) in the pediatric SOT population. We evaluated the impact of different SARS-CoV-2 variants in a cohort of PCR positive SOT recipients. Methods SOT recipients with a positive SARS-CoV-2 PCR test from 3/1/2020 to 2/28/2022 were included in the cohort. The study period was divided into 3 eras based on the predominant circulating variant of SARS-CoV-2: 3/20-6/21 original strain/Alpha, 7/21-11/21 Delta, and 12/21-2/22 Omicron variants. Retrospective medical record review was performed; Chi-squared and Fischer exact test were used to compare groups. Results A total of 269 of 1031 (26%) SOT recipients tested positive for SARS-CoV-2 during the study period. By organ, 87/335 (26%) heart, 57/224 (25%) kidney, 92/405 (23%) liver, and 25/67 (37%) lung recipients had COVID-19 infection. By era, there were 99 (37%) original strain/ Alpha, 65 (24%) Delta, and 105 (39%) Omicron. The patients’ median age was 12.72 years (IQR 6.6, 15.1) with a minority of recipients being female (42%). Common comorbidities included hypertension (50%), obesity (13%), diabetes (10%), and chronic kidney disease (10%); 34% had no comorbidities aside from chronic immunosuppression post-transplant. Overall, 80% of recipients were symptomatic (Figure 1), and 50 (19%) required hospitalization. Hospitalization rates were highest (29%) during Delta, compared with 18% for original/Alpha and 13% for Omicron (p=0.02) eras. Need for respiratory support, ICU admission, and all-cause mortality did not vary by era (Table 1). Three SOT recipients (2 original/Alpha and 1 Delta) were diagnosed with multi-inflammatory syndrome in children (MIS-C). Conclusion Our study suggests that pediatric SOT recipients have a high risk for hospitalization and short-term complications with COVID-19; Omicron appears to cause less severe disease, including MIS-C. Additional studies are needed to understand long-term complications of COVID-19 in SOT recipients. Disclosures Elizabeth A. Moulton, MD, PhD, Pfizer: Grant/Research Support Flor M. Munoz, MD, MSc, Gilead: Grant/Research Support|Moderna: DSMB|Pfizer: DSMB.

In Memoriam Tribute to Jeffrey Robbins, PhD (1950-2022).

In Memoriam Tribute to Jeffrey Robbins, PhD (1950-2022).

Improved Outcomes for Infants and Young Children Undergoing Lung Transplantation at Three Years of Age and Younger.

Rationale: Since its inception, older children and adolescents have predominated in pediatric lung transplantation. Most pediatric lung transplant programs around the world have transplanted few infants and young children. Early mortality after lung transplantation and inadequate donor organs have been perceived as limitations for success in lung transplantation at this age. Objectives: Our aim was to describe our experience in a large pediatric lung transplant program with respect to lung transplantation in infants and young children, focusing on diagnosis, waitlist, and mortality. Methods: We performed a retrospective review of infants and young children under 3 years of age at the time of transplant in our program from 2002 through 2020. Results: The patient cohort represented a severely morbid recipient group, with the majority hospitalized in the intensive care unit on mechanical ventilation just before transplantation. There was a marked heterogeneity of diagnoses distinct from diagnoses in an older cohort. Waitlist time was shorter than in older age cohorts. There was a decrease in early mortality, lowerincidence of allograft rejection, and satisfactory long-term survival in this age group compared with the older cohort and published experience. Severe viral infection was an important cause of early mortality after transplant. Nonetheless, survival is comparable to older patients, with better enduring survival in those who survive the early transplant period in more recent years. Conclusions: Carefully selected infants and young children with end-stage lung and pulmonary vascular disease are appropriate candidates for lung transplantation and are likely underserved by current clinical practice.

Pediatric Hematopoietic Stem Cell Transplantation in Lithuania - 20 Years of Progress through Collaboration.

Hematopoietic stem cell transplantation (HSCT) is a complex procedure that is curative for several fatal pediatric malignancies and non-malignant diseases. Despite its complexity, potential toxicity, and high costs HSCT has become a standard procedure worldwide for several decades. Pediatric HSCT programs encounter several specific challenges. The rarity and heterogeneity of primary diseases, result in an almost 10-fold inferior number of pediatric HSCT as compared to adults. In contrast to the adult programs, where autologous HSCT is more common, allogeneic HSCT (that is more complex) prevails in pediatric setting which is underpinned by a higher number of inborn disorders transplanted in early childhood.In Lithuania, the pediatric HSCT program (EBMT CIC* 508) was launched at Vilnius University Hospital Santaros Klinikos in February 2002. Currently, this is the only specialized pediatric HSCT center in Lithuania and in the Baltic countries. Since 2011 it is a reference center for Latvian children who need autologous or allogeneic transplantation.Here we summarize conference proceedings presented at the scientific event “Pediatric hematopoietic stem cell transplantation in Lithuania – 20 years of progress through collaboration”. The meeting held on September 22-23, 2022, in Vilnius and aimed at commemorating 20 years of the launch of the pediatric transplant program in Lithuania. The event pursued sharing the experience in the field of pediatric HSCT in the Baltic countries. Given a very small population in all three Baltic countries, Lithuania, Latvia, and Estonia face an additional challenge in maintaining sufficient transplant volume and gaining experience. Several distinguished speakers from USA, Denmark, Italy, Germany, Spain, UK and Ukraine shared their expertise in the field and emphasized the crucial role of national and international collaboration to achieve progress in the management of this very rare and complex procedure that offers cure for otherwise fatal pediatric conditions.

Medication Barriers and Adherence: Experiences of Pediatric Transplant Recipients.

This study examined associations between scores on the Adolescent Medication Barriers Scale (AMBS) and the Parent Medication Barriers Scale (PMBS), patient and family factors, and medication adherence outcomes. Patients and caregivers from a pediatric solid organ transplantation (SOT) program were recruited for participation. Pediatric SOT recipients ages 10 to 21 years were eligible for participation. Analyses included reliability analyses and regression modeling with posttransplant medication adherence measured by Medication Level Variability Index scores. Seventy-three patients and caregivers completed an AMBS or PMBS questionnaire. Patient-caregiver inter-rater reliability was poor to fair. Greater medication barriers were reported among younger and female patients and families with more children. AMBS scores predicted greater nonadherence, while the PMBS was not predictive of adherence. Results point to the difficulty of assessing barriers to medication adherence and the lack of agreement between adolescent patients and caregivers. AMBS scores were more closely aligned with medication nonadherence, whereas PMBS scores may have been more influenced by family social factors. Adolescent reports of medication barriers may offer multidisciplinary transplant teams greater clinical utility when addressing these challenges with patients. Transplant social workers and psychologists should engage adolescents and caregivers in efforts to address medication nonadherence.

Vaccines, Antibodies and Donors: Varying Attitudes and Policies Surrounding COVID-19 and Heart Transplantation

IntroductionThere are varied opinions in the United States regarding many aspects of care related to COVID-19. The purpose of this study was to examine the opinions of health care personnel and the policies of heart transplant centers concerning practices for the prevention and treatment of COVID-19 in donors and recipients of heart transplants.MethodsTwo anonymous, electronic web-based surveys were developed: 1 was administered to health care personnel through a mailing list maintained by the Heart Failure Society of America (HFSA); another was administered to U.S. medical adult and pediatric heart transplant (HT) program directors. Individual and group e-mails were sent with an embedded link to the respective surveys in February 2022.ResultsA total of 176 individuals (8.6%) responded to the survey administered through the HFSA. Of medical directors of transplant programs, 78 (54% response rate) completed a separate survey on their centers’ policies. Although 95% (n = 167) of individuals indicated vaccination against COVID-19 should be required prior to HT, only 67% (n = 52) of centers mandated that practice. Similarly, 61% of individuals thought vaccination should be required prior to HT for caregivers, but only 13% of transplant centers mandated caregiver vaccination. Of the centers, 63% reported considering donors despite histories of recent COVID-19 infection (within 3 months), and 47% considered donors with current positive polymerase chain reaction tests. Regarding post-transplant care, only 22% of programs routinely measured antibodies to COVID-19, and 71% used tixagevimab/cilgavimab (Evusheld) for pre-exposure prophylaxis.ConclusionsThere were significant differences between individual preferences and centers’ practices with respect to COVID-19 management of candidates for and recipients of HT. Additionally, there was wide variation in policies among centers, reflecting the need for further study to inform consistent guidance and recommendations across centers to optimize equitable care for this high-risk patient population.

276. SARS-CoV-2 Infection in Solid Organ Transplant Candidates and Recipients at Texas Children’s Hospital: A Retrospective Review

BackgroundTexas Children’s Hospital (TCH) is the largest pediatric solid organ transplant (SOT) program in the US, performing heart, kidney, liver, and lung transplants. Limited data exists about SARS-CoV-2 infection (COVID-19) in the pediatric SOT populations. We evaluated the impact of COVID-19 in a cohort of PCR positive SOT candidates and recipients. We hypothesized that COVID-19 would more severely impact SOT recipients compared to transplant candidates. MethodsPatients with SOT or transplant candidates at TCH with a positive SARS-CoV-2 RT-PCR test since March 1, 2020 to April 12, 2021 were included in the cohort. Retrospective medical record review was performed, and descriptive statistics were used. ResultsA total of 103 SOT patients were identified, 13 candidates and 90 recipients. Of the SOT candidates, there were 1 heart, 3 kidney, and 9 liver transplant candidates. The SOT recipient cohort included 33 heart, 6 lung, 20 kidney, 33 liver and 2 multi-visceral recipients. A significant difference in age was observed between candidates and recipients with candidates being younger with median age of 4.5 years as opposed to recipient’s median age of 12.8 years (p=0.0003). The majority of patients, 70 of 101 (69%), were symptomatic. Most common symptoms reported were fever in 34/70 (49%), cough in 31/70 (44%), and headache in 19/70 (27%). A higher percentage of candidates (31%, 4 of 13) were hospitalized for acute COVID-19 infection compared to (17%, 15 of 90) of recipients. A transplant candidate who ultimately died from underlying illness and COVID-19 was the only patient in the cohort who required mechanical ventilation. More deaths (2/13, 15%) occurred in transplant candidates with COVID-19 compared to transplant recipients with COVID-19 (1/90, 1%, p=0.04); however, 2 of the deaths occurred after recovery from acute COVID-19 illness.ConclusionOur study suggests that pediatric candidates who are actively listed for transplant with underlying conditions have more severe acute COVID-19 illness than pediatric SOT recipients despite their immunosuppression based on the higher mortality observed in the transplant candidates. Prospective studies are needed to better understand which specific patients are at increased risk for mortality from COVID-19.Disclosures Leanne Petters, MSN, APRN, CPNP-AC, Pfizer (Scientific Research Study Investigator) Flor M. Munoz, MD, Biocryst (Scientific Research Study Investigator)Gilead (Scientific Research Study Investigator)Meissa (Other Financial or Material Support, DSMB)Moderna (Scientific Research Study Investigator, Other Financial or Material Support, DSMB)Pfizer (Scientific Research Study Investigator, Other Financial or Material Support, DSMB)Virometix (Other Financial or Material Support, DSMB) Elizabeth A. Moulton, MD, PhD, Pfizer (Scientific Research Study Investigator)

An Italian survey on the use of T-tube in liver transplantation: old habits die hard!

There is enough clinical evidence that a T-tube use in biliary reconstruction at adult liver transplantation (LT) does not significantly modify the risk of biliary stricture/leak, and it may even sustain infective and metabolic complications. Thus, the policy on T-tube use has been globally changing, with progressive application of more restrictive selection criteria. However, there are no currently standardized indications in such change, and many LT Centers rely only on own experience and routine. A nation-wide survey was conducted among all the 20 Italian adult LT Centers to investigate the current policy on T-tube use. It was found that 20% of Centers completely discontinued the T-tube use, while 25% Centers used it routinely in all LT cases. The remaining 55% of Centers applied a selective policy, based on criteria of technical complexity of biliary reconstruction (72.7%), followed by low-quality graft (63.6%) and high-risk recipient (36.4%). A T-tube use > 50% of annual caseload was not associated with high-volume Center status (> 70 LT per year), an active pediatric or living-donor transplant program, or use of DCD grafts. Only 10/20 (50%) Centers identified T-tube as a potential risk factor for complications other than biliary stricture/leak. In these cases, the suspected pathogenic mechanism comprised bacterial colonization (70%), malabsorption (70%), interruption of the entero-hepatic bile-acid cycle (50%), biliary inflammation due to an indwelling catheter (40%) and gut microbiota changes (40%). In conclusion, the prevalence of T-tube use among the Italian LT Centers is still relatively high, compared to the European trend (33%), and the potential detrimental effect of T-tube, beyond biliary stricture/leak, seems to be somehow underestimated.

A systematic approach to transplanting non-resident, non-citizens in an established US pediatric lung transplant program.

IntroductionThe Texas Children’s Hospital Lung Transplant Program undertook consideration of its first non-resident, non-citizen for lung transplantation in 2011.MethodsFour referrals from the Royal Embassy of Saudi Arabia were received, and two patients were evaluated from 2011 to 2013.ResultsAfter a suitable candidate and family was identified, the program adopted a systematic approach to ensure that all the necessary elements of pre-transplant care, informed consent, and post-transplant care could be effectively delivered.ConclusionThe use of hospital translation services and the development of a strong professional relationship with a well-trained pediatric respirologist in Saudi Arabia combined with an excellent early post-transplant clinical course provide lessons that may be of help to other transplant programs considering international patients as candidates for solid organ transplantation.

Impact of COVID-19 Pandemic on Pediatrics and Pediatric Transplantation Programs.

COVID-19 has dramatically altered the health care landscape and disrupted global health and world economics in ways that are still being measured. Its impact on children with chronic conditions or those undergoing transplantation is evolving. The organ specific manifestations in children will be reviewed and treatment strategies outlined. The impact on pediatric transplantation in the United States over the initial 6 months of the pandemic has shown significant regional variation and lags persist in resumption of normal transplant activity, particularly for living related transplantation. Finally, guidelines regarding return to school will be discussed.

Pediatric HCT in Florida (2014 -2016): A report from the FPBCC.

FPBCC was formed in 2018 by five pediatric transplant programs in Florida. One of the key objectives of the consortium is to provide outcome analyses by combining HCT data from all the participating centers in order to identify areas for improvement. In this first FPBCC landscape report we describe the patient and transplant characteristics of pediatric patients undergoing first allo and auto HCT between 2014 and 2016 in Florida. The source of data was eDBtC of the CIBMTR. Over the span of 3years, a total of 230 pediatric patients underwent allo-HCT and 104 underwent auto-HCT at the participating centers. The most significant predictor of survival in allo-HCT recipients with malignant disorders was the degree of HLA- match, while in the recipients of allo-HCT with non-malignant disorders the predictors of survival included age, donor relationship and degree of HLA match. Our analyses identified the need to improve reporting of primary cause of death and improve on donor selection process given that the degree of HLA match remains the most important predictor of survival. This first FPBCC-wide review describes the trends in pediatric HCT activity between 2014 and 2016 among the participating centers in Florida and confirms feasibility of using eDBtC data platform and collaborative approach in order to identify areas for improvement in outcomes.

Variability in Surveillance Monitoring and Management of Donor-Specific Antibodies Among Pediatric Transplant Programs Participating in the Improving Renal Outcomes Collaborative (IROC)

Variability in Surveillance Monitoring and Management of Donor-Specific Antibodies Among Pediatric Transplant Programs Participating in the Improving Renal Outcomes Collaborative (IROC)

Considerations for Pediatric Heart Programs During COVID-19: Recommendations From the Congenital Cardiac Anesthesia Society.

Considerations for Pediatric Heart Programs During COVID-19: Recommendations From the Congenital Cardiac Anesthesia Society.

Preparing for the Implementation of an Agnis Enabled Data Reporting System and Comprehensive Research Level Data Repository for All Cellular Therapy Patients

Background Dana-Farber Cancer Institute (DFCI) includes both a pediatric and adult transplant program. Though there are many shared resources each program is accredited individually, and they are separate CIBMTR reporting centers. With consistent growth and increasingly demanding reporting requirements, it was determined that one comprehensive internal database that filled the needs of both programs was necessary. Aim/Goals Establish a comprehensive internal database that streamlined multiple unmet needs within two large cellular therapy programs including: • Pre and post therapy case management data • Ability to fulfill all CIBMTR regulatory reporting requirements • A comprehensive research level data repository for all cellular therapy patients Methods • Workgroups were formed to map out the current and future state workflow • Gaps in the workflow and areas of vulnerability and data entry duplication were identified • Testing scripts were developed and data entry into the test environment began • During the testing period end user job aids were created and modified • Entry into historical data systems halted prior to • Electronic and manual data conversion began • Data management staff validated the historical data converted to the new system • End users were trained in preparation of software go-live • Full production database was successfully launched • Throughout this process meetings were held between the pediatric and adult joint working group to share best practices and pinpoint opportunities for collaboration. Conclusions • You don't what you don't know • The amount of time dedicated to rolling out the new system and the magnitude of change that accompanied this was far larger than anyone could anticipate • The time commitment required of team members placed significant constraints on completion of their day-to-day responsibilities • Adapting to the new system with confidence and ease took much longer than originally projected • Data managers shifted pre-transplant data entry to real time, allowing case coordinators and clinical staff to access data during the patient's work-up period • A better understanding of the correlation between the pre and post transplant data was realized Next steps • Continue progress on the work flow mapping project to solidify job roles • Maintain system stability by implementing change control policies • Preserve data integrity with newly developed audit and validation guidelines