Madigan, Theresa

Abstract Background Revaccination is required for patients who receive a hematopoietic cell transplant (HCT) to reduce vaccine preventable illness. Revaccination requires an individualized plan due to differences in immunosuppressive therapy, immune reconstitution, age, and other challenges such as graft versus host disease. A structured approach is required to ensure prompt initiation of re-vaccinations and completion of the re-vaccination schedule. This study sought to evaluate the re-vaccination process at our center as a baseline for quality improvement. Methods We conducted a retrospective chart review of pediatric patients who received an autologous or allogeneic HCT between January 2019 and March 2024 to assess time to starting re-vaccination after post-HCT medical clearance and percentage of patients up to date within each series of vaccinations per internal protocol. Results A total of 64 patients were evaluated, of whom 23 were female and 35 underwent allogeneic stem cell transplant. For analysis, 13 were excluded due to death prior to clearance for vaccination. Among those included, 42 patients were cleared for restarting vaccines, and 37 (88%) of those have received at least one vaccine, while only 25 (59%) have completed the first series of recommended vaccines. The average time from transplant to administration of the first vaccine was 431 days for autologous HCT and 459 days for allogeneic HCT. The average time from medical clearance to the first vaccine was 66 days. The mean interval between the first and second vaccine doses was 97 days. Conclusion The majority of eligible patients initiated re-vaccination after transplant, but rates for the receipt of full recommended initial series remained suboptimal, with notable delays with notable delays between transplant and the day of clearance as well as clearance and the first vaccine administered. These findings highlight significant gaps in post-transplant immunization practices and underscore the need for targeted interventions to optimize protection for this vulnerable population. Disclosures All Authors: No reported disclosures

ABSTRACT Background Patients at high risk for cytomegalovirus (CMV) infection after allogeneic hematopoietic stem cell transplant (HCT) should receive CMV prophylaxis. Historically, ganciclovir has been the preferred agent. However, its side effect profile, particularly myelosuppression, is undesirable. Letermovir is a newer agent that is not myelosuppressive and has replaced ganciclovir as the preferred agent for CMV prophylaxis in high‐risk adult patients. Methods The primary objective was to compare the incidence of dose modifications or discontinuation of CMV prophylaxis between pediatric patients who received ganciclovir versus letermovir. Secondary objectives included comparing the use of granulocyte colony‐stimulating factor (G‐CSF) support and the incidence of CMV DNAemia. We reviewed records of all pediatric patients who received an HCT at our institution between 2000 and 2024 and received either ganciclovir/valganciclovir or letermovir for CMV prophylaxis. Results Between 2000 and 2024, 65 pediatric patients receiving prophylactic ganciclovir, valganciclovir, or letermovir were evaluated. The median age at transplant was 12.2 years. No patients receiving letermovir required dose modification or discontinuation as opposed to 14 (29.2%) patients receiving ganciclovir ( p = 0.014). After engraftment, 12 (25%) patients receiving ganciclovir required G‐CSF support compared to seven (41.2%) patients receiving letermovir ( p = 0.23). In the ganciclovir group, 10 (20.8%) patients experienced CMV infection versus one (5.9%) patient receiving letermovir ( p = 0.26). Conclusion Compared with those receiving letermovir, a significantly higher proportion of patients in the ganciclovir/valganciclovir group experienced dose modifications or discontinuation of CMV prophylaxis due to adverse effects. Letermovir shows great promise as a CMV prophylactic agent in pediatric HCT patients due to its favorable side effect profile.

Abstract Background SARS-CoV-2 vaccination has been shown to prevent severe disease and subsequent secondary infections in immunocompromised patients. This study assessed the rate of SARS-CoV-2 vaccinations among pediatric solid organ transplant (SOT) recipients at a single transplant center.Figure 1.SARS-CoV-2 vaccination status among pediatric solid organ transplant recipients for all ages and by age group. Methods We retrospectively reviewed medical records of pediatric recipients of heart, kidney, and liver transplants at Mayo Clinic, Rochester, MN between January 2011 and December 2023. All SARS-CoV-2 vaccine doses administered on or before April 1, 2024 were recorded. Up-to-date (UTD) status was based on current CDC recommendations for immunocompromised patients for each age group. Deceased patients, those no longer following at Mayo Clinic and whose vaccine records were unavailable were excluded. We also assessed whether patients had been seen by an ID physician in the year prior to collection stop date. Results The study included 136 patients: 48 kidney, 58 heart and 30 liver transplant recipients; 52.9% were male. Two patients subsequently received organs of a different type. Mean age was 16.1 years. Since authorization in 2020, 90 patients (66.2%) received at least one SARS-CoV-2 vaccine. This varied by age group, with 72.8% of > =12 year olds, 40.0% of 5-11 year olds and 62.5% of under 5 year olds (p = 0.007 [Figure 1]). Seventy-three patients (53.7%) completed at least three doses. Based on current recommendations that include the 2023-2024 formulation, 30 patients (22.0%) were UTD. This did not differ between age groups (p = 0.717) or by transplanted organ type (p = 0.21). Patients that saw ID were significantly more likely to be UTD (p = 0.001). Among partially immunized patients, 95% (n = 57) needed one additional dose to be UTD. Conclusion Despite simplified guidelines with fewer doses needed, a third of pediatric SOT recipients remain unvaccinated against SARS-CoV-2 and only 22% are UTD based on current recommendations. The proportion of unvaccinated patients was highest in the 5-11 year old age group and lowest in the oldest. Those that recently saw ID were significantly more likely to be UTD. Our data suggest that continued care provided by ID physicians may increase vaccine uptake, but reasons for undervaccination and strategies to counteract this should be further explored within this vulnerable population. Disclosures All Authors: No reported disclosures

ABSTRACTIntroductionThere is a lack of data regarding SARS‐CoV‐2 vaccination rates and tixagevimab‐cilgavimab (TC) uptake among pediatric solid organ transplant recipients. The purpose of our study was to assess these rates.Materials and MethodsWe reviewed vaccination records of pediatric recipients of heart, kidney, and liver transplants at Mayo Clinic, Rochester, MN, who received a transplant between January 2011 and December 2021. All SARS‐CoV‐2 vaccines and doses of TC received on or before September 1, 2022, the date of approval of the bivalent SARS‐CoV2 vaccine, were included. We also assessed whether patients had been seen by an infectious diseases physician (ID) in the preceding 6 months.ResultsOur study included 110 patients: 47 kidney, 36 heart, and 27 liver transplant recipients. All vaccine doses recorded were monovalent SARS‐CoV‐2 vaccines. Sixty‐eight (61.8%) patients received at least one vaccine. This varied by age group, with f of ≥12 years olds, 40.9% of 5–11 year olds and 14.3% of under 5 year olds (p = 0.001). Seven patients (6.4%) were up‐to‐date (UTD) for age. There was no difference in UTD status by organ type (p = 0.335). Patients who saw ID were significantly more likely to be UTD (13.2% versus 2.8%; p = 0.047). Among those eligible, 14 (18.2%) received TC, with rates not different based on transplanted organ type (p = 0.158) or whether they saw ID (p = 0.273).ConclusionsDespite the availability of vaccines, nearly 40% of pediatric solid organ transplant recipients remained unvaccinated against SARS‐CoV‐2 at time of the bivalent vaccine release. Less than a fifth of eligible patients received TC. Strategies to increase uptake of SARS‐CoV‐2 vaccines as well as adjunctive agents among this vulnerable group should be further explored.

Abstract Background Vaccine preventable infections (VPIs) are a significant cause of hospitalizations and morbidity and mortality for pediatric solid organ transplant (SOT) recipients. In this single-center study, we assessed up-to-date (UTD) status of routine childhood immunizations among our institution’s pediatric SOT recipients. Methods We collected immunization data on all pediatric patients who underwent liver, kidney, or heart transplants between January 1, 2011 and December 31, 2021 at Mayo Clinic, Rochester, MN by retrospectively reviewing electronic medical record data. We also assessed whether patients were evaluated by a pediatric infectious diseases (PID) specialist within 1 year of transplant. Immunization status was determined using the CDC child and adolescent immunization schedule, excluding seasonal influenza and SARS-CoV-2 immunizations. Results A total of 143 patients were included in our study (n = 45 liver, 54 kidney, 44 heart recipients); 49.7% were male. At the time of transplant, 39 patients were considered UTD (27.3% [Figure 1]). There was no difference by organ type (p = 0.59) and whether patients had seen PID prior to transplant (p = 0.17). Excluding live viral vaccinations, 45 patients were UTD (31.5%). Human papillomavirus was the least UTD vaccine series (Figure 2). Most patients were not UTD in just one or two series (Figure 1). A significant difference in UTD status was found based on age at transplant (p = 0.03), with younger patients having higher rates of UTD status (mean age 7.1 [SD 5.75] vs 9.9 [SD 5.92] years).Figure 1.Vaccination status of pediatric SOT recipients at time of transplant and number of incomplete series.Figure 2.Vaccination status by series for eligible pediatric SOT recipients. Conclusion To date, this study is the largest cohort of pediatric SOT recipients of three organ types assessing routine childhood vaccination status. In this single-center cohort spanning 11 years, we found that less than a third of patients were UTD on routine childhood immunizations at the time of transplant. While some immunizations can be given post-transplant, every effort should be made to update vaccines among transplant candidates to optimize efficacy and protection, thereby reducing the consequences of VPIs within this vulnerable population. Further studies are needed to address reasons for under-immunization and develop strategies to improve vaccination rates. Disclosures All Authors: No reported disclosures

Introduction: Invasive candidiasis has a high morbidity and mortality among premature neonates. Antifungal prophylaxis with fluconazole significantly lowers the risk of invasive fungal infection in this population. We noted the use of fluconazole prophylaxis in our level IV neonatal intensive care unit (NICU) was variable and sought to standardize prescribing of prophylactic fluconazole. Methods: We formed a multidisciplinary team to develop an evidence-based protocol using literature and expert consensus to guide appropriate use of fluconazole prophylaxis in our level IV NICU. After determining baseline fluconazole prophylaxis prescribing before protocol implementation, we used plan-do-study-act (PDSA) cycles to introduce protocolized prescribing and incorporate it into daily practice. A 6-month intervention phase was followed by a 2-year control phase, in which monthly audits were performed to evaluate protocol adherence. Results were displayed in a statistical process control chart. Results: Before protocol implementation, fluconazole prophylaxis prescribing adhered to the protocol in 81% of patients. During the first PDSA cycle, adherence increased significantly to 94.5% (86/91 patients), which further increased to 98.7% (74/75 patients) during the second PDSA cycle and remained at 96% (120/125 patients) during the control phase (P < 0.0001). Conclusions: A multidisciplinary group-designed protocol was successful in standardizing fluconazole prophylaxis prescribing for infants in the level IV NICU. Adherence to protocol was high following implementation and was sustained for the duration of the project. There were no cases of invasive candidiasis noted.

AbstractBackgroundSolid organ transplant (SOT) recipients are at increased risk of vaccine‐preventable illness due to the high degree of immunosuppression required following transplantation. The current recommendation is to vaccinate with live attenuated vaccines, including Measles, Mumps, and Rubella (MMR) and Varicella (VAR) vaccines, at least 4 weeks prior to transplant. However, data to support the time interval between vaccine and transplant are limited.MethodsWe conduct a literature review of the natural history of the viruses and length of viremia following live‐attenuated viral vaccines, and we describe a series of 5 cases from 2 pediatric transplant centers in which live attenuated viral vaccines were administered within 21 days prior to SOT.ResultsNone of the 5 children who received MMR or VAR 8‐21 days prior to liver (2) and heart (3) transplant suffered from vaccine‐related viral illness after transplant, even in the presence of significant immunosuppression with T‐cell‐depleting agents.ConclusionThese cases support that shorter intervals of live vaccine administration prior to transplant may be safe, allowing the vaccination of a larger cohort of SOT candidates. Increasing pretransplant vaccinations is crucial since, in most cases, live viral vaccines are contraindicated posttransplantation, and the most effective vaccine approaches utilize prime‐boost strategies, priming before and boosting after transplant.