Evaluation of a Reverse Transcription-Quantitative Polymerase Chain Reaction (RT-qPCR)-Based Microneutralization Assay for Assessing Clinical Human Cytomegalovirus-Neutralizing Antibody Activity.

Development of a vaccine for human cytomegalovirus (hCMV) is critical because of the severe consequences of infection in congenitally infected newborns and immunocompromised patients. The assessment of hCMV-neutralizing antibody activity is crucial for vaccine development. This study evaluated a RT-qPCR assay targeting the immediate-early gene transcript of hCMV for determining microneutralizing antibody activity.

The IPTA Nashville consensus conference on Post-Transplant lymphoproliferative disorders after solid organ transplantation in children: II-consensus guidelines for prevention.

The International Pediatric Transplant Association (IPTA) convened an expert consensus conference to assess current evidence and develop recommendations for various aspects of care relating to post-transplant lymphoproliferative disorder after solid organ transplantation in children. In this report from the Prevention Working Group, we reviewed the existing literature regarding immunoprophylaxis and chemoprophylaxis, and pre-emptive strategies. While the group made a strong recommendation for pre-emptive reduction of immunosuppression at the time of EBV DNAemia (low to moderate evidence), no recommendations for use could be made for any prophylactic strategy or alternate pre-emptive strategy, largely due to insufficient or conflicting evidence.

The IPTA Nashville consensus conference on post-transplant lymphoproliferative disorders after solid organ transplantation in children: I-Methodology for the development of consensus practice guidelines.

The International Pediatric Transplant Association (IPTA) Consensus Conference on Practice Guidelines for the Diagnosis, Prevention, and Management of Post-Transplant Lymphoproliferative Disorders after Solid Organ Transplantation in Children took place on March 12-13, 2019, and the work of conference members continued until the end of December 2021. The goal was to produce evidence-based consensus guidelines on the definitions, diagnosis, prevention, and management of PTLD and related disorders based on the critical review of the literature and consensus of experts. This report describes the goals, organization, and methodology of the consensus conference and follow-up activities.

Hyperammonemia syndrome post-lung transplantation: Case series and systematic review of literature.

Background: Hyperammonemia syndrome (HS) is a rare post-transplant complication associated with high morbidity and mortality. Its incidence appears to be higher in lung transplant recipients and its pathophysiology is not well understood. In addition to underlying metabolic abnormalities, it is postulated that HS may be associated with Ureaplasma or Mycoplasma spp.

Tumor Infiltrating Lymphocytes Predict Survival in Solid Organ Transplant Recipients With Monomorphic Post-transplant Lymphoproliferative Disorders.

Introduction: The tumor microenvironment (TME) in post-transplant lymphoproliferative disorders (PTLDs) remains unexplored. Tumor infiltrating lymphocytes (TILs) are prognostic in other lymphomas. We assessed the prognostic impact of TILs in monomorphic B-cell PTLD.

Cytomegalovirus transmission in mismatched solid organ transplant recipients: Are factors other than anti-viral prophylaxis at play?

Although antiviral prophylaxis has reduced cytomegalovirus (CMV) DNAemia and disease in seronegative solid organ transplant (SOT) recipients (R-) receiving seropositive donor organs (D+), its impact on CMV transmission is uncertain. Transmission, defined as CMV antigenemia/CMV DNAemia and/or seroconversion by year 2, and associated demographic risk factors were studied retrospectively in 428 D+/R- and 429 D-/R- patients receiving a SOT at our center. The cumulative transmission incidence was higher for lung (90.

Association between Mycoplasma and Ureaplasma airway positivity, ammonia levels, and outcomes post-lung transplantation: A prospective surveillance study.

Hyperammonemia syndrome (HS) is a rare complication with high mortality described after lung transplantation. Its pathophysiology is still unclear, but previous studies, including murine models, have linked the identification of Mycoplasmataceae in airway specimens with HS occurrence. This study explores the association between Mycoplasmataceae polymerase chain reaction (PCR) positivity, ammonia levels, HS, and mortality post-lung transplant.

Using blood donors and solid organ transplant donors and recipients to estimate the seroprevalence of cytomegalovirus and Epstein-Barr virus in Canada: A cross-sectional study.

Background: Cytomegalovirus (CMV) and Epstein-Barr virus (EBV) infections are common, causing significant morbidity in pregnancy (congenital CMV) and transplant recipients (CMV, EBV). Canadian prevalence data are needed to model disease burden and develop strategies for future vaccines. We estimated prevalence using screening data from blood donors and solid organ transplant (SOT) donors and recipients.

Classic Hodgkin lymphoma post-transplant lymphoproliferative disorders (PTLD) are often preceded by discordant PTLD subtypes.

Classic Hodgkin lymphoma (CHL) is the rarest post-transplant lymphoproliferative disorder (PTLD) subtype. Few cases of patients with metachronous discordant PTLD episodes including CHL-PTLD have been reported, but the incidence of and risk factors for this phenomenon are unknown. Patients with CHL-PTLD were identified from an institutional PTLD database.

Donor Cytomegalovirus Transmission Patterns in Solid Organ Transplant Recipients With Primary Infection.

Background: The epidemiology of single versus multiple cytomegalovirus (CMV) strain transmission from donor (D+) to seronegative solid organ transplant (SOT) recipients (R-) is uncertain, as is whether "relapsing" recipient infection represents changing strain predominance when multiple strains are transmitted. Here we characterized CMV strain transmission patterns in D+/R- SOT recipients.

Methods: We studied pairs or groups of D+/R- SOT recipients who received organs from a common donor (group A) and recipients who experienced ≥2 waves of CMV DNAemia (group B).

Transfusion-transmitted and community-acquired cytomegalovirus infection in seronegative solid organ transplant recipients receiving seronegative donor organs.

Solid organ transplant (SOT) recipients who are cytomegalovirus (CMV) seronegative (R-) and receive seronegative donor (D-) organs have a small but currently unquantified risk of both transfusion-transmitted CMV (TT-CMV) and community-acquired CMV (CA-CMV). We retrospectively studied the incidence and clinical symptoms of TT-CMV (infection <1 year posttransplant) and CA-CMV (infection >1 year posttransplant) in a cohort of D-/R- adult and pediatric SOT recipients receiving leukoreduced blood products not screened for CMV seronegativity transplanted at our center between 2000 and 2011. CMV infection was defined as IgG seroconversion or detectable CMV antigenemia/DNAemia.

Post-transplant lymphoproliferative disorders, Epstein-Barr virus infection, and disease in solid organ transplantation: Guidelines from the American Society of Transplantation Infectious Diseases Community of Practice.

These updated guidelines from the American Society of Transplantation Infectious Diseases Community of Practice review the diagnosis, management, and prevention of post-transplant lymphoproliferative disorders (PTLD) and other Epstein-Barr virus (EBV) syndromes after solid organ transplantation. PTLD are a heterogeneous spectrum of predominantly B-cell disorders, often extra-nodal, with complex distinct pathogeneses and variable clinical presentations determined by pathologic subtype. Recent epidemiologic studies report a decrease in early EBV-positive (+) PTLD and an increase in late EBV-negative (-) PTLD.

High incidence of clinically significant cytomegalovirus infection in CMV D+/R+ lung transplant recipients receiving 3 months of antiviral prophylaxis.

Background: Universal antiviral prophylaxis is the preferred preventive strategy for lung transplant recipients (LTRs) at risk of CMV infection. We compared the risk of CMV infection between CMV D+/R + and D-/R + LTRs after 3 months of prophylaxis.

Methods: This was a retrospective review of CMV R + LTRs transplanted between 2005 and 2013.

CMV-specific T-cells and CD27-CD28-CD4+ T-cells for assignment of cytomegalovirus (CMV) status in adults awaiting organ transplant.

Background/objectives: Determination of Cytomegalovirus (CMV) status in solid organ transplant (SOT) candidates is essential to stratify risk of post-transplant CMV disease. Passive transfusion-acquired antibodies can make serologic determination of CMV status unreliable. We evaluated 3 assays, not affected by passive antibodies (PA), in assignment of CMV status: quantification of CMV-specific CD4 + T-cells (CMV-TC) and exhausted CD27-CD28- CD4 + T-cells, and detection of CMV DNA with Nucleic Acid Amplification Testing (NAAT).

Impact of donor and recipient cytomegalovirus serology on long-term survival of heart transplant recipients.

Background: Some studies have shown that pre-transplant cytomegalovirus (CMV) serostatus is associated with heart transplant patient survival while others have not. We analyzed the relationship between pre-transplant donor/recipient CMV serostatus and long-term mortality in a retrospective cohort of heart transplant recipients at our center.

Methods: Adult (Age >17 years) heart recipients transplanted between July 1985-December 2015 were analyzed.

Epstein-Barr virus associated smooth muscle tumors in solid organ transplant recipients: Incidence over 31 years at a single institution and review of the literature.

Introduction: Epstein-Barr virus (EBV) associated smooth muscle tumors (EBV-SMT) are a rare complication of solid organ transplantation (SOT). Incidence data related to this EBV-SMT are limited. EBV DNA is universally present in these tumors.

Impact of donor and recipient cytomegalovirus serology on long-term survival of lung transplant recipients.

Background: Pre-transplant cytomegalovirus (CMV) serostatus has been associated with lung transplant patient survival. We retrospectively analyzed the relationship between pre-transplant donor/recipient CMV serostatus and long-term mortality in a cohort of lung transplant recipients at our center.

Method: Adult (Age >17 years) lung recipients transplanted between July 1985-December 2015 were analyzed.

Assigning Cytomegalovirus Status in Children Awaiting Organ Transplant: Viral Shedding, CMV-Specific T Cells, and CD27-CD28-CD4+ T Cells.

Passive antibodies, maternal or transfusion-acquired, make serologic determination of pretransplant cytomegalovirus (CMV) status unreliable. We evaluated 3 assays unaffected by passive antibodies, in assignment of CMV infection status in children awaiting solid organ transplant and in controls: (1) CMV nucleic acid amplification testing (NAAT), (2) quantification of CMV-specific CD4+ T cells, and (3) quantification of CD27-CD28-CD4+ T cells. Our results highlight that CMV NAAT, from urine and oropharynx, is useful in confirming positive CMV status.

Assignment of cytomegalovirus infection status in infants awaiting solid organ transplant: Viral detection methods as adjuncts to serology.

Assignment of CMV infection status in infants awaiting SOT is challenging as passive maternal antibody can lead to false-positive serology. Since 2000, our protocol has recommended sending throat and urine samples for CMV viral detection, culture, or NAAT, for CMV-seropositive infants <18 months awaiting SOT. We reviewed pretransplant CMV serology for 152 infants and, for CMV seropositives, examined relationships between CMV IgG OD values, age, and CMV viral detection to explore time to clearance of maternal CMV IgG and evaluate viral detection in assignment of pretransplant CMV infection status.

The Changing Epidemiology of Posttransplant Lymphoproliferative Disorder in Adult Solid Organ Transplant Recipients Over 30 Years: A Single-center Experience.

Background: Posttransplant lymphoproliferative disorders (PTLD) are a complication of solid organ transplantation (SOT) associated with Epstein-Barr virus (EBV).

Methods: We analyzed the incidence of and risk factors for PTLD among adult SOT recipients at our center over 30 years (1984-2013). We also compared PTLD incidence before and after a prevention strategy of EBV viral load monitoring in EBV serology mismatched patients was adapted in 2001 (ie, transplant era 1 [1983-2001] vs era 2 [2002-2013]).

Determination of the Biological Form of Human Cytomegalovirus DNA in the Plasma of Solid-Organ Transplant Recipients.

Background: Whether cytomegalovirus (CMV) DNA exists in plasma as virion-associated or free DNA is uncertain.

Methods: An assay combining DNase I digestion and CMV quantitative polymerase chain reaction (DNase-CMV-qPCR) was developed to differentiate free naked DNA from virion DNA. One hundred three frozen and 10 fresh CMV DNA-positive plasma samples from solid-organ transplant recipients (SOTRs) were tested.

Radiation Exposure from Diagnostic Imaging in a Cohort of Pediatric Transplant Recipients.

Recipients of solid organ transplants (SOT) have extensive diagnostic imaging (DI). The purpose of this study was to quantify this exposure. Children from northern Alberta with SOTs at Stollery Children's Hospital, Edmonton, Alberta January 1, 2006, to July 31, 2012, were included.