Publications by authors named "Madeleine R Heldman"

Article Synopsis
  • EBV DNAemia surveillance is used to prevent post-transplant lymphoproliferative disorder (PTLD) in lung transplant recipients (LTRs), but its effectiveness in adult seropositive patients is unclear.
  • A study analyzed EBV viral loads in seropositive LTRs and compared levels between those who developed PTLD and those who didn't, revealing that peak viral loads were only significantly higher after PTLD was suspected.
  • The study found low positive predictive values (PPVs) for moderate (14.7%) and high-grade (33.3%) EBV DNAemia in indicating risk for future PTLD, suggesting improved diagnostic approaches are needed.
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Article Synopsis
  • Belatacept is used to prevent rejection in lung transplant patients, but the infection risks associated with its use haven't been thoroughly studied.
  • A retrospective study analyzed infections in 52 lung transplant recipients treated with belatacept from 2011 to 2022, revealing significant rates of viral and bacterial infections, particularly cytomegalovirus (CMV).
  • The findings highlight the need for collaborative research to further investigate infection risks and management strategies for lung transplant recipients receiving belatacept.
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Article Synopsis
  • - Recent advancements in cytomegalovirus (CMV) prevention and treatment have emerged from pivotal clinical trials, focusing on tailored strategies for hematopoietic cell transplantation (HCT) and solid organ transplantation (SOT).
  • - The review highlights methods to boost CMV-specific immunity using vaccination, monoclonal antibodies, and virus-specific T-cells, alongside observational studies on CMV cell-mediated immunity assays to refine preventive and treatment approaches.
  • - Emphasizing the need to enhance CMV-specific immunity is vital for reducing CMV's detrimental effects in transplant recipients, especially as infections in CAR-T therapy patients and other immunocompromised groups rise, although these areas are not covered in this review.
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Background: Plasma microbial cell-free DNA (mcfDNA) sequencing can establish the etiology of multiple infectious syndromes by identifying microbial DNA in plasma. However, data are needed to define the clinical scenarios where this tool offers the highest clinical benefit.

Methods: We conducted a prospective multicenter observational study that evaluated the impact of plasma mcfDNA sequencing compared with usual care testing among adults with hematologic malignancies.

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Article Synopsis
  • - Researchers studied maribavir (MBV) to treat 15 cases of difficult-to-treat cytomegalovirus infections in 13 solid organ transplant patients.
  • - Nearly half of the treatment episodes (47%) faced failure because of new MBV resistance or virus returning soon after stopping the medication.
  • - On the positive side, 40% of the treatment episodes resulted in sustained viral clearance, meaning the virus was eliminated effectively.*
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The Comparison of Antiviral Preventative Strategies In Liver Transplant (CAPSIL) study showed pre-emptive therapy (PET) to be superior to antiviral prophylaxis for Cytomegalovirus (CMV) disease prevention in high-risk CMV seronegative liver transplant recipients (LTRs) with seropositive donors (DR). Despite the statistical superiority of PET over prophylaxis in research settings, PET is perceived as a logistically more complex strategy that requires careful coordination of weekly CMV PCR testing, prompt initiation of CMV antivirals upon viremia detection, and timely cessation of antivirals following viremia resolution. Transplant centers may be hesitant to use PET for CMV disease prevention in DR LTRs out of concern that PET coordination is not feasible in clinical practice.

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The authors summarize recent updates in the prevention and management of cytomegalovirus (CMV) in solid organ transplant (SOT) recipients with a focus on CMV seronegative recipients of organs from seropositive donors (CMV D+/R-) who are at highest risk of CMV infection and disease. They discuss advantages of preemptive therapy for CMV disease prevention in CMV D+/R- liver transplant recipients, letermovir for CMV prophylaxis, and updates in the development of monoclonal antibodies and vaccines as immune-based preventative strategies. They review the roles of maribavir and virus-specific T cells for management of resistant or refractory CMV infection in SOT recipients.

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Background: Plasma microbial cell-free DNA sequencing (mcfDNA-Seq) is a noninvasive test for microbial diagnosis of invasive mold infection (IMI). The utility of mcfDNA-Seq for predicting IMI onset and the clinical implications of mcfDNA concentrations are unknown.

Methods: We retrospectively tested plasma from hematopoietic cell transplant (HCT) recipients with pulmonary IMI and ≥1 mold identified by mcfDNA-Seq in plasma collected within 14 days of clinical diagnosis.

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Background: Despite superiority of preemptive therapy (PET) compared to universal prophylaxis for prevention of cytomegalovirus (CMV) disease in the CAPSIL randomized trial among CMV D+R- liver transplant recipients (LTxRs), real-world effectiveness may be lower because of logistical concerns about feasibility of PET.

Methods: We retrospectively assessed PET as standard clinical care at a single transplant center among 50 consecutive adult CMV D+R- LTxRs undergoing a first liver transplant between 4/4/2019 and 5/18/2021 and compared outcomes and adherence to those randomized to PET in the CAPSIL study (N = 100). The primary outcome was CMV disease and secondary outcomes were biopsy-confirmed acute allograft rejection, retransplant, invasive fungal infections, and death, all assessed by 1-year post-transplant.

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Background: Epstein-Barr virus (EBV) seronegative solid organ transplant recipients (SOTRs) are at increased risk for post-transplant lymphoproliferative disorder (PTLD). Assays for EBV serostatus assess antibody to both EBV viral capsid antigen (VCA) and Epstein-Barr nuclear antigen-1 (EBNA-1), but PTLD risk among SOT recipients with discordant VCA and EBNA-1 results is unknown.

Methods: We performed a retrospective, single-center cohort study to determine the risk of PTLD among adult (≥ 18 years) SOTRs with discordant pre-transplant VCA and EBNA-1 IgG compared to that of SOTRs with concordantly negative or concordantly positive serology using univariable and multivariable Cox-proportional hazards models.

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Introduction: Most studies of solid organ transplant (SOT) recipients with COVID-19 focus on outcomes within one month of illness onset. Delayed mortality in SOT recipients hospitalized for COVID-19 has not been fully examined.

Methods: We used data from a multicenter registry to calculate mortality by 90 days following initial SARS-CoV-2 detection in SOT recipients hospitalized for COVID-19 and developed multivariable Cox proportional-hazards models to compare risk factors for death by days 28 and 90.

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Background: Herpes simplex virus (HSV) 1 and 2, varicella zoster virus (VZV), and human herpesvirus 6 (HHV-6) cause severe infections in immunocompromised hosts. Interventions to optimize virus-specific adaptive immunity may have advantages over antivirals in the prophylaxis and treatment of these infections.

Objectives: We sought to review adaptive immune responses and methods for assessing and replenishing cellular and humoral immunity to HSV, VZV, and HHV-6 in solid organ transplant and hematopoietic cell transplant recipients.

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Purpose Of Review: Management of Epstein-Barr virus posttransplant lymphoproliferative disorder (EBV PTLD) is complex, involving risk stratification, prevention and/or preemptive measures involving monitoring EBV DNAemia and balancing treatment options, using a combination of reduction of immune suppression, anti-B cell therapy, and cytotoxic T lymphocytes (CTLs).

Recent Findings: The highest risk factor for the development of EBV PTLD in hematopoietic cell transplant (HCT) remains T cell depletion, with increasing use of antithymocyte globulin (ATG) or alemtuzumab in conditioning. In solid organ transplantation (SOT), the incidence of PTLD is highest among EBV seronegative recipients who are at risk for primary EBV infection following transplant in the first 12 months.

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Mortality among patients hospitalized for COVID-19 has declined over the course of the pandemic. Mortality trends specifically in solid organ transplant recipients (SOTR) are unknown. Using data from a multicenter registry of SOTR hospitalized for COVID-19, we compared 28-day mortality between early 2020 (March 1, 2020-June 19, 2020) and late 2020 (June 20, 2020-December 31, 2020).

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Pneumonia due to cytomegalovirus and herpes simplex virus-1 caused substantial morbidity after hematopoietic cell transplantation before the institution of preventative approaches. End-organ disease from herpesviruses is poorly described after chimeric antigen receptor-modified T-cell immunotherapy. We report 2 cases of cytomegalovirus pneumonia and 1 case of herpes simplex virus-1 gingivostomatitis, esophagitis, and pneumonia after chimeric antigen receptor-modified T-cell immunotherapy for the treatment of hematologic malignancies.

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"Outcomes of COVID-19 in solid organ transplant (SOT) recipients: a matched cohort study" by Pereira et al found similar 28 day mortality among hospitalized SOT recipients and comorbidity matched controls, shedding light on the relationship between immunosuppression and Covid-19 outcomes.

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Purpose Of Review: The approach to ongoing organ transplantation and management of COVID-19 in solid organ transplant recipients (SOTR) has evolved tremendously since the pandemic's beginning. We summarize the current literature surrounding the virology of SARS-CoV-2, epidemiology of COVID-19 in transplant recipients, review the clinical features and complications of COVID-19 in SOTR, and discuss the safety and efficacy of current therapies and candidate vaccines in this population.

Recent Findings: Despite initial suspensions in organ transplantation during early 2020, routine donor testing and de-crowding of hospitals have allowed transplant activity to resume at pre-pandemic rates.

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Reactivation of human herpesvirus 6 (HHV-6) after allogeneic hematopoietic cell transplantation (HCT) is associated with neurologic complications, but the impact of donor and/or recipient inherited chromosomally integrated HHV-6 (iciHHV-6) on post-HCT central nervous system (CNS) symptoms and diagnostic and therapeutic interventions is not well understood. The aims of the present study were (1) to compare the cumulative incidence of CNS symptoms in the first 100 days following allogeneic HCT among patients with donor and/or recipient iciHHV-6 (iciHHV-6)with that of patients with neither donor nor recipient iciHHV-6 (iciHHV-6) and (2) to assess the role of HHV-6 detection in driving potentially unnecessary interventions in iciHHV-6 patients. We performed a retrospective matched cohort study of 87 iciHHV-6 and 174 iciHHV-6 allogeneic HCT recipients.

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Lung transplant recipients (LTR) with coronavirus disease 2019 (COVID-19) may have higher mortality than non-lung solid organ transplant recipients (SOTR), but direct comparisons are limited. Risk factors for mortality specifically in LTR have not been explored. We performed a multicenter cohort study of adult SOTR with COVID-19 to compare mortality by 28 days between hospitalized LTR and non-lung SOTR.

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