Approach to suspected donor-derived infections

Prevention of donor-derived disease among pediatric solid organ transplant recipients requires judicious risk-benefit assessment. Comprehensive guidelines outline specific donor risk factors and post-transplant monitoring strategies to prevent and mitigate transmission of HIV, hepatitis B, and hepatitis C. However, elimination of unanticipated donor-derived infections remains challenging. The objectives of this review are to (1) define risk of anticipated vs. unanticipated disease transmission events in pediatric solid organ transplant recipients; (2) discuss donor presentations that confer greater risk of unanticipated disease transmission; (3) develop a matrix for consideration of donor acceptance; and (4) discuss limitations and future directions for donor screening. Although solid organ transplant confers inherent risk of infection transmission, the risk of significant disease transmission events may be mitigated by a comprehensive approach including donor assessment, consideration of recipient need, post-transplant monitoring, and early intervention

Usefulness of gene expression profiling of bronchoalveolar lavage cells in acute lung allograft rejection.

BackgroundChronic lung allograft dysfunction (CLAD) is the main limitation to long-term survival after lung transplantation. Because effective therapies are lacking, early identification and mitigation of risk factors is a pragmatic approach to improve outcomes. Acute cellular rejection (ACR) is the most pervasive risk factor for CLAD, but diagnosis requires transbronchial biopsy, which carries risks. We hypothesized that gene expression in the bronchoalveolar lavage (BAL) cell pellet (CP) could replace biopsy and inform on mechanisms of CLAD.MethodsWe performed RNA sequencing on BAL CPs from 219 lung transplant recipients with A-grade ACR (n = 61), lymphocytic bronchiolitis (n = 58), infection (n = 41), or no rejection/infection (n = 59). Differential gene expression was based on absolute fold difference >2.0 and Benjamini-adjusted p-value ≤0.05. We used the Database for Annotation, Visualization and Integrated Discovery Bioinformatics Resource for pathway analyses. For classifier modeling, samples were randomly split into training (n = 154) and testing sets (n = 65). A logistic regression model using recursive feature elimination and 5-fold cross-validation was trained to optimize area under the curve (AUC).ResultsDifferential gene expression identified 72 genes. Enriched pathways included T-cell receptor signaling, natural killer cell-mediated cytotoxicity, and cytokine-cytokine receptor interaction. A 4-gene model (AUC = 0.72) and classification threshold defined in the training set exhibited fair performance in the testing set; accuracy was 76%, specificity 82%, and sensitivity 60%. In addition, classification as ACR was associated with worse CLAD-free survival (hazard ratio = 2.42; 95% confidence interval = 1.29-4.53).ConclusionsBAL CP gene expression during ACR is enriched for immune response pathways and shows promise as a diagnostic tool for ACR, especially ACR that is a precursor of CLAD

β-Herpesviruses in Febrile Children with Cancer

These viruses should be included in the differential diagnosis of febrile disease

The Third International Consensus Guidelines on the Management of Cytomegalovirus in Solid-organ Transplantation

Despite recent advances, cytomegalovirus (CMV) infections remain one of the most common complications affecting solid organ transplant recipients, conveying higher risks of complications, graft loss, morbidity, and mortality. Research in the field and development of prior consensus guidelines supported by The Transplantation Society has allowed a more standardized approach to CMV management. An international multidisciplinary panel of experts was convened to expand and revise evidence and expert opinion-based consensus guidelines on CMV management including prevention, treatment, diagnostics, immunology, drug resistance, and pediatric issues. Highlights include advances in molecular and immunologic diagnostics, improved understanding of diagnostic thresholds, optimized methods of prevention, advances in the use of novel antiviral therapies and certain immunosuppressive agents, and more savvy approaches to treatment resistant/refractory disease. The following report summarizes the updated recommendations

COVID-19 in pediatric kidney transplantation: The Improving Renal Outcomes Collaborative.

There are limited data on the impact of COVID-19 in children with a kidney transplant (KT). We conducted a prospective cohort study through the Improving Renal Outcomes Collaborative (IROC) to collect clinical outcome data about COVID-19 in pediatric KT patients. Twenty-two IROC centers that care for 2732 patients submitted testing and outcomes data for 281 patients tested for SARS-CoV-2 by PCR. Testing indications included symptoms and/or potential exposures to COVID-19 (N = 134, 47.7%) and/or testing per hospital policy (N = 154, 54.8%). Overall, 24 (8.5%) patients tested positive, of which 15 (63%) were symptomatic. Of the COVID-19-positive patients, 16 were managed as outpatients, six received non-ICU inpatient care and two were admitted to the ICU. There were no episodes of respiratory failure, allograft loss, or death associated with COVID-19. To estimate incidence, subanalysis was performed for 13 centers that care for 1686 patients that submitted all negative and positive COVID-19 results. Of the 229 tested patients at these 13 centers, 10 (5 asymptomatic) patients tested positive, yielding an overall incidence of 0.6% and an incidence among tested patients of 4.4%. Pediatric KT patients in the United States had a low estimated incidence of COVID-19 disease and excellent short-term outcomes

New developments in treatment after lung transplantation

Lung transplantation has evolved as an accepted therapy in selected adults and children with end-stage lung disease. Outcomes following lung transplantation have improved in the recent era with a 5-year survival of > 70% and an overall good functional status of surviving recipients. Many of the advances have been achieved by the use of modern immunosuppressive agents. To date, multiple strategies exist that may be employed when utilizing immunosuppression. These agents can be used in a variety of roles that may include induction, maintenance or rescue therapy, many of which are illustrated in this review including the current evidence to support their use. Infections in lung transplant recipients remain a significant cause of morbidity and mortality. Special considerations are required with the substantial burden of chronic infection in candidates with CF lung disease before transplantation, which are discussed. Furthermore, recent progress and advances in prevention and treatment of post-transplantation infectious complications are detailed. Chronic lung allograft dysfunction remains to be the burden of lung transplantation in the long-term. Unfortunately, there is no well-established therapy to address it. However, therapy attempts include change/augmentation of immunosupression, use of neomacrolides and extracorporeal photopheresis, all of which are reviewed in detail

476. A Global Survey of Countermeasures Against the COVID-19 Pandemic Among Solid Organ Transplant Centers

AbstractBackgroundSolid organ transplantation (SOT) profoundly impacts vulnerable recipients with chronic end organ diseases. The COVID-19 pandemic disrupted healthcare systems, including organ transplants. We aimed to evaluate the responses of SOT centers to COVID-19 at the beginning of the pandemic around the world.MethodsWe conducted a web-based survey amongst transplant centers, sent to members of The American Society of Transplantation Infectious Diseases Community of Practice Group, between April and May 2020. The survey included basic information of each transplant center (number and types of transplants in 2019), the countermeasures employed against COVID-19 such as timing of postponing of transplantation, and management of outpatient clinics including implementation of telemedicine and screening for in-person visits.ResultsA total of 65 centers from 19 countries responded (Table 1). Regarding the percentage of hospitalized patients with COVID-19 at the time of the survey, 39 (60%) centers reported 80%. All centers reduced their services to some extent as shown in Table 2. Centers reported postponing living donor kidney transplant (50/58, 86%), deceased donor kidney transplant (20/57, 35%), living donor liver transplant (32/42, 80%), deceased donor liver transplant (17/41, 41%), lung transplant (20/31, 65%), heart transplant for LVAD (18/33, 55%) and non-LVAD patients (18/33, 55%). In March and April 2020, cancellation of pre- and post- transplant clinics were reported by 36/64 (56%) and 17/65 (26%) centers. Postponing clinic appointments were reported by 56/65 (86%) centers. Most institutions (54/64, 85%) used telemedicine. Screening for COVID-19 for clinic visits was done by telephone, in-person questionnaires and/or temperature checks.ConclusionDuring the early phase of the pandemic, when management strategies were highly uncertain, non-urgent and living donor transplants were frequently postponed. Emergent liver transplants continued regardless. These findings could help us navigate SOT in future epidemics. Limitations included a small sample and lack of assessment of clinical outcomes from postponing SOT.DisclosuresDeepali Kumar, MD, MSc, FRCPC, Astellas (Individual(s) Involved: Self): Speakers’ bureau; Atara Biotherapeutics (Individual(s) Involved: Self): Grant/Research Support; GSK (Individual(s) Involved: Self): Consultant, Grant/Research Support; Merck (Individual(s) Involved: Both Myself and my Spouse/Partner): Advisor or Review Panel member, Grant/Research Support; Oxford immunotec (Individual(s) Involved: Self): Consultant, Grant/Research Support; Pfizer (Individual(s) Involved: Self): Speakers’ bureau; Roche (Individual(s) Involved: Self): Consultant, Grant/Research Support; Sanofi (Individual(s) Involved: Self): Advisor or Review Panel member; Shire/Takeda (Individual(s) Involved: Both Myself and my Spouse/Partner): Advisor or Review Panel member, Grant/Research Support Lara Danziger-Isakov, MD, MPH, Ansun (Individual(s) Involved: Self): Scientific Research Study Investigator; Astellas (Individual(s) Involved: Self): Scientific Research Study Investigator; Merck (Individual(s) Involved: Self): Consultant, Scientific Research Study Investigator; Pfizer (Individual(s) Involved: Self): Scientific Research Study Investigator; Shire (Individual(s) Involved: Self): Consultant, Scientific Research Study Investigator; Viracor: Grant/Research Suppor

Cytomegalovirus in Pediatric Hematopoietic Stem Cell Transplantation: A Case-Based Panel Discussion of Current Challenges

Cytomegalovirus (CMV) remains a significant contributor to morbidity and death after pediatric solid and stem cell transplantation. Decisions regarding prevention and treatment often lack pediatric-specific data to drive decision making. We present here a case-based discussion around some of these specific topics and focus on approaches to CMV prevention, post-CMV secondary prophylaxis options, and identification and treatment of resistant CMV infection, including emerging antiviral agents and the use of cytotoxic CMV-specific T-cells, in the setting of pediatric hematopoietic stem cell transplantation