American Society Of Transplantation Research Articles

Summary of a consensus conference on heart-liver transplantation

Patients with severe heart disease may have coexisting liver disease from various causes. The incidence of combined heart-liver transplant (CHLT) is increasing as more patients with congenital heart disease survive to adulthood and develop advanced heart failure with associated liver disease from chronic right-sided heart or Fontan failure. However, the criteria for CHLT have not been established. To address this unmet need, a virtual consensus conference was organized on June 10, 2022, endorsed by the American Society of Transplantation. The conference represented a collaborative effort by experts in cardiothoracic and liver transplantation from across the United States to assess interdisciplinary criteria for liver transplantation in the CHLT candidate, surgical considerations of CHLT, current allocation system that generally results in the liver following the heart for CHLT, and optimal post-CHLT management. The conference served as a forum to unify criteria between the different specialties and to forge a pathway for patients who may need dual organ transplantation. Due to the continuing shortage of available donor organs, ethical issues related to multiorgan transplantation were also debated. The findings and consensus statements are presented.

518. Comparable Outcomes of Remdesivir and Sotrovimab among High-risk Patients with Mild to Moderate COVID-19 During the Omicron BA.1 Surge

Abstract Background Two independent placebo-controlled clinical trials conducted prior to SARS-CoV-2 Omicron demonstrated that sotrovimab and remdesivir reduced hospitalization among high-risk outpatients with mild to moderate COVID-19. However, their effectiveness have not been directly compared. Methods This retrospective study examined all high-risk outpatients with mild to moderate COVID-19 who received either remdesivir or sotrovimab at Mayo Clinic during the Omicron BA.1 surge from January to March 2022. COVID-19-related hospitalization or death within 28 days were compared between the two treatment groups. Results Among 3,257 patients, 2,158 received sotrovimab and 1,099 received remdesivir. Patients treated with sotrovimab were younger (median age, 60 vs. 69 years) and had lower comorbidity (Monoclonal Antibody Screening Score, 5 vs. 6; Charlson Comorbidity Index, 3 vs. 4), but were more likely to be immunocompromised (47.3% vs. 30.2%) than remdesivir-treated patients. The majority (89%) had received at least one dose of COVID-19 vaccine (median, 3 doses [IQR 2-3] for both groups). COVID-19-related hospitalization (1.5% and 1.0% in remdesivir and sotrovimab groups, respectively, p=.15) and mortality within 28 days (0.4% in both groups, p=.82) were similarly low. A propensity score weighted analysis demonstrated no significant difference in the rates of COVID-related hospitalization and death within 28 days between the two groups. Conclusion This study demonstrated favorable outcomes that were not significantly different between patients treated with remdesivir or sotrovimab. As sotrovimab is no longer authorized, these results support the continued use of remdesivir for treating high-risk patients with COVID-19 during the current Omicron-predominant epoch. Disclosures Christina G. Rivera (O'Connor), Pharm.D, Gilead Sciences: Advisor/Consultant|Gilead Sciences: Board Member|Gilead Sciences: Grant/Research Support|Gilead Sciences: Honoraria Maria Gonzalez Suarez, M.D., Ph.D., Gilead: Grant/Research Support Ravindra Ganesh, M.B.B.S., M.D., Alpaca Health: Advisor/Consultant Raymund R. Razonable, MD, Allovir: Endpoint Adjudication Committee|American Society of Transplantation: Board Member|Gilead: Grant/Research Support|Novartis: DSMB|Regeneron: Grant/Research Support|Roche: Grant/Research Support

Early and Consistent CRS Detection Using Wearable Device for Remote Patient Monitoring Following CAR-T Therapy in Relapsed/Refractory Multiple Myeloma (RRMM): Early Results of an Investigator-Initiated Trial

The administration of Chimeric Antigen Receptor T-cell (CAR-T) therapy for relapsed refractory multiple myeloma (RRMM) predominantly takes place in the inpatient setting to monitor for adverse effects like cytokine release syndrome (CRS) and neurotoxicity leading to increased healthcare utilization, infection risk and patient discomfort. Shifting the administration model to the outpatient setting may improve patient experience, optimize hospital bed utilization and decrease costs, but requires an objective and reliable method for CRS detection to monitor patients remotely and safely. The feasibility of using a wearable device for detecting CRS following CAR-T therapy in RRMM was compared to standard of care (SoC) nursing-recorded vital signs in this investigator initiated clinical trial (IIT). Patients wore a wearable device that collected continuous measures of temperature, pulse, respiratory rate, and O2 saturation in addition to SoC while receiving CAR-T therapy from the day infusion to discharge. Changes in vital signs captured by the device were analyzed based on 2 thresholds: (i) CRS timestamps were tagged in wearable data when pt's temperature breached a fixed threshold of 38 0C ( Tf) defined as fever by the American Society of Transplantation and Cellular Therapy (ASTCT), and (ii) when pt's temperature breached an individualized threshold of 2 standard deviations above their baseline temperature ( Ti) [see Figure 1]. Outcomes were time to first detection of CRS in wearable data vs. SoC. Wearable adherence was the duration pts wore the device over the total monitoring period. To date, 34 pts were screened, 28 enrolled (82.3% uptake), 1 was excluded from the dataset because of concurrent COVID-19, and 2 pts with CRS were excluded from time to detection comparison because of wearable adherence <50% during high-risk windows (defined as the time period where CRS is expected per known data for the CAR-T product). Max CRS grades were 1 (17 pts), 2 (1 pt), 3 (2 pts), and 4 (1 pt); 5 pts did not have clinical CRS. Patients wore the device for a median of 13 (12-15) days out of a median of 15.5 (14-17) days of inpatient admission for CAR-T infusion. Median individualized temperature threshold was 37.4 (37-37.6) C. Wearable adherence was 64 (51 - 77) % and 72 (57 - 87) % for the overall monitoring and high-risk periods, respectively. The wearable detected the initial CRS events at a median of 22 (-43 - 113.5) min earlier than SoC with Tf and a median of 184 (53 - 312) mins earlier than SoC with Ti method. In the no CRS subgroup, false CRS detection occurred in 1 pt with the Tf and 2 pts with the Ti method. Preliminary results suggest that time to CRS detection by the wearable device preceded SoC detection by a median of 103 minutes corroborated by both threshold methods. Temperature thresholds calibrated to the baseline temperature of individual patients facilitate earlier detection of CRS than fixed thresholds per clinical/ASTCT criteria. While the low false detection rate in is encouraging, these may also potentially be attributed to subclinical events. Both pts who had “false positive” triggers breached their individualized temperature thresholds via device readings while only recording low-grade temperatures that did not meet clinical CRS criteria per ASTCT, indicating possible capture of subclinical events. The study showcases the utility of continuous remote patient vital signs monitoring by wearable devices in efficiently capturing CRS, including subclinical events, earlier than SoC. Objective and reliable CRS monitoring may help safely transition workflows to outpatient CAR-T administration models. Analysis of trends in cytokine biomarkers for early CRS detection signal(s) is currently underway. Cytokine signals, alone and in combination with device data, are planned to be incorporated into machine learning models to build a CRS prediction index in future analyses. Figure 1: Snapshot in time of the continuous temperature data generated by the wearable device after CAR-T infusion showing capture of cytokine release syndrome. – Ti (solid line) represents the median baseline temperature of the patient over the entire duration of the data capture by the wearable device – Tf (dotted line) represents the temperature threshold of 38 0C, the clinical definition of fever as per ASTCT – Black diamond: clinical CRS event, when temperature >38 0C as recorded by nursing

Lessons learned: Development of an organ transplant caregiver educational resource.

Organ transplant lay caregivers perform an essential and complex role, but there is a paucity of comprehensive, accessible education regarding transplant caregiving. We sought to create a broad, multifaceted educational toolkit for transplant caregivers. Given the complexities of this population, we report on lessons learned by organising diverse stakeholder engagement to develop an educational resource covering the breadth and depth of organ transplantation. Following a call from organ transplant patients and caregivers, the American Society of Transplantation (AST) formed an Organ Transplant Caregiver Initiative with the aim to develop a comprehensive educational toolkit for transplant caregivers. The AST Organ Transplant Caregiver Toolkit was created through a shared, multi-step process involving transplant professionals and caregivers, who formed an education subcommittee to develop and refine content domains. The caregiver toolkit was reviewed with relevant external stakeholders and through an internal organisational review process. Lessons learned included seeking guidance from others with experience creating similar resources, flexibility in project development, creativity in engaging stakeholders and routine communication between all entities involved. Insights gained contributed to the caregiver toolkit completion despite project challenges. The AST Organ Transplant Caregiver Toolkit can be utilised by health care professionals to educate and counsel transplant patients and caregivers. Lessons learned from the development of the caregiver toolkit can provide guidance to health care professionals and clinical teachers for the development of future education resources.

A deep learning framework for personalised dynamic diagnosis of graft fibrosis after liver transplantation: a retrospective, single Canadian centre, longitudinal study

Recurrent graft fibrosis after liver transplantation can threaten both graft and patient survival. Therefore, early detection of fibrosis is essential to avoid disease progression and the need for retransplantation. Non-invasive blood-based biomarkers of fibrosis are limited by moderate accuracy and high cost. We aimed to evaluate the accuracy of machine learning algorithms in detecting graft fibrosis using longitudinal clinical and laboratory data. In this retrospective, longitudinal study, we trained machine learning algorithms, including our novel weighted long short-term memory (LSTM) model, to predict the risk of significant fibrosis using follow-up data from 1893 adults who had a liver transplantation between Feb 1, 1987, and Dec 30, 2019, with at least one liver biopsy post transplantation. Liver biopsy samples with indefinitive fibrosis stage and those from patients with multiple transplantations were excluded. Longitudinal clinical variables were collected from transplantation to the date of last available liver biopsy. Deep learning models were trained on 70% of the patients as the training set and 30% of the patients as the test set. The algorithms were also separately tested on longitudinal data from patients in a subgroup of patients (n=149) who had transient elastography within 1 year before or after the date of liver biopsy. Weighted LSTM model performance for diagnosing significant fibrosis was compared against LSTM, other deep learning models (recurrent neural network and temporal convolutional network), and machine learning models (Random Forest, Support vector machines, Logistic regression, Lasso regression, and Ridge regression) and aspartate aminotransferase-to-platelet ratio index (APRI), fibrosis-4 index (FIB-4), and transient elastography. 1893 people who had a liver transplantation (1261 [67%] men and 632 [33%] women) with at least one liver biopsy between Jan 1, 1992, and June 30, 2020, were included in the study (591 [31%] cases and 1302 [69%] controls). The median age at liver transplantation was 53·7 years (IQR 47·3-59·0) for cases and 55·3 years (48·0 to 61·2) for controls. The median time interval between transplant and liver biopsy was 21 months (5 to 71). The weighted LSTM model (area under the curve 0·798 [95% CI 0·790 to 0·810]) consistently outperformed other methods, including unweighted LSTM (0·761 [0·750 to 0·769]; p=0·031) Recurrent Neural Network (0·736 [0·721 to 0·744]), Temporal Convolutional Networks (0·700 [0·662 to 0·747], and Random Forest 0·679 [0·652 to 0·707]), FIB-4 (0·650 [0·636 to 0·663]) and APRI (0·682 [0·671 to 0·694]) when diagnosing F2 or worse stage fibrosis. In a subgroup of patients with transient elastography results, weighted LSTM was not significantly better at detecting fibrosis (≥F2; 0·705 [0·687 to 0·724]) than transient elastography (0·685 [0·662 to 0·704]). The top ten variables predictive for significant fibrosis were recipient age, primary indication for transplantation, donor age, and longitudinal data for creatinine, alanine aminotransferase, aspartate aminotransferase, total bilirubin, platelets, white blood cell count, and weight. Deep learning algorithms, particularly weighted LSTM, outperform other routinely used non-invasive modalities and could help with the earlier diagnosis of graft fibrosis using longitudinal clinical and laboratory variables. The list of most important predictive variables for the development of fibrosis will enable clinicians to modify their management accordingly to prevent onset of graft cirrhosis. Canadian Institute of Health Research, American Society of Transplantation, Toronto General and Western Hospital Foundation, and Paladin Labs.

Editorial introductions.

Current Opinion in Cardiology was launched in 1985. It is part of a successful series of review journals whose unique format is designed to provide a systematic and critical assessment of the literature as presented in the many primary journals. The field of cardiology is divided into 14 sections that are reviewed once a year. Each section is assigned a Section Editor, a leading authority in the area, who identifies the most important topics at that time. Here we are pleased to introduce the Journal's Editor and Section Editors for this issue. SECTION EDITORS Ali J MarianAli J MarianDr Marian received his training in clinical cardiology and human molecular genetics at Baylor College of Medicine, Houston, USA. He was appointed as a faculty at the Section of Cardiology at Baylor College of Medicine, Houston, USA in 1992. He joined the Institute of Molecular Medicine in 2006 to lead the Center for Cardiovascular Genetics. Dr Marian is recognized for his research achievements in molecular genetics and clinical aspects of cardiomyopathies. He has published over 200 articles in peer-reviewed journals, which collectively have garnered over 12,000 citations and an H index of 60. He received the Young Investigator Award from the American College of Cardiology, the Established Investigator Award from the American Heart Association, the Clinician-Scientist Award in Translational Research from Burroughs Wellcome Fund, Distinguished Scientist Award from Baylor St Luke's Medical Center, and the Best Editor Award from the American Heart Association Circulation Research. Dr Marian is currently a Deputy Editor for Cardiovascular Research, Section Editor on Genetics for Current Opinion in Cardiology, and the Editor-in-Chief of The Journal of Cardiovascular Aging. He is a former Deputy Editor for Circulation Research, Associate Editor for Circulation and European Journal of Clinical Investigation. Dr Marian's research is supported by R01 grants from the NHLBI-NIH, Leducq Foundation Trans-Atlantic Network of Excellence, and local foundations. Gene KimGene KimDr Kim is a cardiologist with the Advanced heart failure, Cardiac transplant, and Mechanical Circulatory Support Program at the University of Chicago Medicine, USA. He is an Associate Professor of Medicine and the Advanced Heart Failure Fellowship Program Director. His medical school, residency, and fellowship training were completed at the University of Chicago, USA. Dr Kim also directs the Genetic Cardiomyopathy and Hypertrophic Cardiomyopathy Clinics at University of Chicago, USA. Dr Kim's research interests include the genetic and epigenetic regulation of heart failure and arrhythmogenesis with publications on the role of microRNAs in cardiomyopathy. His interests also include myocardial recovery, extracellular matrix in failing myocardium. He has published over 100 articles and book chapters and is an investigator in numerous clinical trials. Bhavadharini RamuBhavadharini RamuDr Bhavadharini (Dharini) Ramu is an Advanced Heart Failure & Transplant Cardiologist, Director of the Cardio-Obstetrics Program and an Associate Professor of Medicine at the University of Minnesota, USA. She completed her internal medicine residency and cardiology fellowship at the University of Connecticut, USA followed by Advanced Heart Failure Fellowship at the University of Minnesota, USA in 2016. She previously served on the faculty at the Medical University of South Carolina, USA from 2016 to 2023. Dr Ramu has been an invited faculty lecturer at scientific meetings of the American College of Cardiology (ACC), Heart Failure Society of America, American Society of Transplantation, and International Society of Heart & Lung Transplantation. She is a member of the ACC's Heart Failure & Transplant Section Leadership Council, the program planning committee for the ACC's Scientific Sessions, and serves on the leadership council of the Women in Heart Transplantation & MCS Network. Dr Ramu's research interests include increasing the understanding of and reducing the impact of health-related disparities in patients with advanced heart failure, with a goal of reducing health inequities and improving the health of disadvantaged and vulnerable populations. She has served as a peer reviewer for many journals and is an investigator in heart failure clinical trials.

Prevention, diagnosis, and management of donor derived infections in pediatric kidney transplant recipients.

Donor derived infections (DDIs) in pediatric kidney transplant recipients remain challenging to diagnose and can result in serious morbidity and mortality. This review summarizes the current guidelines and recommendations for prevention, diagnosis, and treatment of unexpected DDIs in pediatric kidney transplant recipients. We provide a contemporary overview of DDI terminology, surveillance, epidemiology, and recommended approaches for assessing these rare events with an emphasis on the pediatric recipient. To address prevention and risk mitigation, important aspects of donor and pediatric candidate evaluations are reviewed, including current Organ Procurement and Transplantation Network (OPTN) and American Society of Transplantation (AST) recommendations. Common unexpected DDI encountered by pediatric transplant teams including multi-drug resistant organisms, tuberculosis, syphilis, West Nile Virus, toxoplasmosis, Chagas disease, strongyloidiasis, candidiasis, histoplasmosis, coccidioidomycosis, and emerging infections such as COVID-19 are discussed in detail. Finally, we consider the general challenges with management of DDIs and share our experience with a novel application of next generation sequencing (NGS) of microbial cell-free DNA that will likely define a future direction in this field.

Financial, policy, and ethical barriers to the expansion of living donor liver transplant: Meeting report from a living donor liver transplant consensus conference.

In October 2021, the American Society of Transplantation (AST) hosted a virtual consensus conference aimed at identifying and addressing barriers to the broader, safe expansion of living donor liver transplantation (LDLT) throughout the United States (US). A multidisciplinary group of LDLT experts convened to address issues related to financial implications on the donor, transplant center crisis management, regulatory and oversight policies, and ethical considerations by assessing the relative significance of issues in preventing LDLT growth, with proposed strategies to overcome barriers. Living liver donors endure multiple obstacles including financial instability, loss of job security, and potential morbidity. These concerns, along with other center, state, and federal specific policies can be perceived as significant barriers to expanding LDLT. Donor safety is of paramount importance to the transplant community; however, regulatory and oversight policies aimed at ensuring donor safety can be viewed as ambiguous and complicated leading to time-consuming evaluations that may deter donor motivation and program expansion. Transplant programs need to establish appropriate crisis management plans to mitigate potential negative donor outcomes and ensure program viability and stability. Finally, ethical aspects, including informed consent for high-risk recipients and use of non-directed donors, can be perceived as additional barriers to expanding LDLT.

Lorlatinib Induces Rapid and Durable Response in Refractory Anaplastic Lymphoma Kinase-Positive Large B-Cell Lymphoma.

Article Tools CASE REPORTS Article Tools OPTIONS & TOOLS Export Citation Track Citation Add To Favorites Rights & Permissions COMPANION ARTICLES No companion articles ARTICLE CITATION DOI: 10.1200/PO.22.00536 JCO Precision Oncology no. 7 (2023) e2200536. Published online February 21, 2023. Lorlatinib Induces Rapid and Durable Response in Refractory Anaplastic Lymphoma Kinase–Positive Large B-Cell Lymphoma Baldeep Wirk , MD1xBaldeep WirkSearch for articles by this author; Jozef Malysz, MD1xJozef MalyszSearch for articles by this author; Esther Choi, MD1xEsther ChoiSearch for articles by this author; and Natthapol Songdej, MD1xNatthapol SongdejSearch for articles by this author Show More 1Penn State College of Medicine, Hershey, PA https://doi.org/10.1200/PO.22.00536 First Page Full Text PDF Figures and Tables © 2023 by American Society of Clinical OncologyPRIOR PRESENTATIONThe abstract of this manuscript was previously presented as a poster at the American Society of Transplantation & Cellular Therapy Meetings, Salt Lake City, UT, April 23-26, 2022.AUTHOR CONTRIBUTIONSConception and design: Baldeep Wirk, Jozef Malysz, Natthapol SongdejAdministrative support: Natthapol SongdejCollection and assembly of data: Baldeep Wirk, Jozef Malysz, Natthapol SongdejData analysis and interpretation: Baldeep Wirk, Jozef Malysz, Natthapol SongdejManuscript writing: All authorsFinal approval of manuscript: All authorsAccountable for all aspects of the work: All authorsAUTHORS' DISCLOSURES OF POTENTIAL CONFLICTS OF INTERESTThe following represents disclosure information provided by authors of this manuscript. All relationships are considered compensated unless otherwise noted. Relationships are self-held unless noted. I = Immediate Family Member, Inst = My Institution. Relationships may not relate to the subject matter of this manuscript. For more information about ASCO's conflict of interest policy, please refer to www.asco.org/rwc or ascopubs.org/po/author-center.Open Payments is a public database containing information reported by companies about payments made to US-licensed physicians (Open Payments).Natthapol SongdejConsulting or Advisory Role: Blueprint MedicinesNo other potential conflicts of interest were reported.

Editorial introductions.

Editorial introductions.

212. Outcomes of Weekly Fluconazole Antifungal Prophylaxis in Pancreas Transplant Recipients

Abstract Background Fungal infections following pancreas transplantation carry significant morbidity and mortality with an estimated incidence of 3 to 28%. The American Society of Transplantation (AST) suggests considering fluconazole prophylaxis in pancreas transplant recipients (PTR) at high-risk of invasive candidiasis (IC). However, optimal dosage and duration of prophylaxis is unclear. Weekly fluconazole for prevention of IC has been previously reported in liver and bone marrow transplant recipients. We analyzed outcomes of once weekly fluconazole prophylaxis in PTR. Methods We retrospectively reviewed all pancreas transplants performed at our institution from January 2017 through September 2021. PTR at high-risk for IC were defined per AST criteria as those with enteric drainage, vascular thrombosis, and post-perfusion pancreatitis. Patients received once weekly oral fluconazole 200 mg for 12 weeks post-transplant for IC prophylaxis. We analyzed incidence of breakthrough IC within the first 6 months post-transplant. Results We identified a total of 22 PTR, all of whom received simultaneous kidney transplantation from deceased donors. Of these, 12/22 (55%) were male and 11/22 (50%) were African American. Median age at the time of transplantation was 39 years (IQR 34-46). The most common indication for transplantation was type 1 diabetes mellitus (17/22, 21%) with associated nephropathy. No donor organ cultures were positive for fungi and all pancreas transplants were performed using enteric drainage. Notably, one patient developed pancreas allograft thrombosis while another developed pancreatitis. No patients required early discontinuation of fluconazole due to intolerance or side effects and none developed breakthrough IC within 6 months post-transplant (Table 1). Table 1. Conclusion Weekly fluconazole prophylaxis has not been previously studied in PTR. In our cohort, this approach was well tolerated, with no cases of IC at 6 months post-transplantation in patients at high-risk. Randomized controlled clinical trials are needed to define the optimal strategy in this population. Disclosures M. Rizwan Sohail, MD, Aziyo Biologics: Honoraria|Boston Scientific Corporation: Honoraria|Medtronic: Grant/Research Support|TRYX: Grant/Research Support.

630. A Single-Center 10-Year Analysis of Immunizations in Heart Transplant Recipients

Abstract Background Vaccine-preventable diseases pose a risk towards heart transplant recipients on lifelong immunosuppression. Immunization rates are low (30-80%) in solid organ transplants. The aim of this study was to examine the vaccination rates in our hospital’s heart transplant recipients with a goal to expose deficiencies and formulate strategies to increase vaccination in this population. Methods This study is a single-center retrospective chart review of patients aged 18 or older who received a heart transplant between January 1, 2012 and March 31, 2022 at our institution in Temple, Texas. We documented vaccination status or seropositivity prior to or after transplant, as recommended by the American Society of Transplantation (AST) for influenza, hepatitis B, hepatitis A, measles, mumps, and rubella (MMR), 23-valent pneumococcal polysaccharide (PPSV23), 13-valent pneumococcal conjugate (PCV13), tetanus, diphtheria, and acellular pertussis (Tdap), varicella, zoster, and COVID-19 immunizations. We evaluated the association with an Infectious Disease (ID) consult. Odds ratios (OR) were calculated with 95% confidence intervals. Results 72 patients received a heart transplant within the 10-year period. Demographics are noted in table 1. Table 2 presents the immunization status as follows: 48.7% for flu vaccine, 55.5% for Hepatitis B, 47.1% for Hepatitis A, 36.1% for MMR, 67.5% for PPSV23, 67.5% for PCV13, 54.1% for Tdap, 83.3% for Varicella and 13.8% for Zoster, and 53.5% for COVID-19. From 2016, an ID consult was required pre-transplant; 45 patients (62.5%) had an ID consult before transplant. ID consult was associated with increased likelihood of receiving the MMR, PCV13, Tdap, and Zoster vaccines (table 3). Table 1Patient demographics Table 2 Immunization status in heart transplant recipients Table 3 Immunization status associated with ID consult Conclusion This study reveals the deficiency of vaccinations in our heart transplant patients, but an ID consult was associated with better immunization rates. To further increase compliance, we propose different interventions including close follow-up with ID, addressing vaccine costs, accessibility limitations, cultural hesitancy, and implementation of protocols. Disclosures All Authors: No reported disclosures.

1587. Clinical Utility of a Cytomegalovirus (CMV)-specific T Cell Assay in Assessing the Risk of Post-Prophylaxis CMV Infection and Post-Treatment Relapse

Abstract Background Cytomegalovirus (CMV) causes significant morbidity in solid organ transplant recipients (SOTR). As a lack of immunity predisposes to infection, a laboratory test that measures CMV-specific cell-mediated immunity (CMV CMI) may help guide antiviral prophylaxis, predict relapses and correlate with outcomes. We assessed CMV CMI in CMV D+/R- patients during valganciclovir primary prophylaxis and in CMV viremic SOTRs during antiviral treatment, and correlated the results with post-prophylaxis CMV infection and post-treatment relapse, respectively. Methods CMV CMI was assessed in two groups of SOTRs using the QuantiFERON© CMV interferon-gamma release assay (IGRA), with level >0.2 IU/mL suggestive of immunity. The first group included CMV D+/R- SOTRs who underwent monthly CMV CMI testing during 6 months of valganciclovir prophylaxis. These patients were prospectively followed for CMV episodes for 1 year post transplant. The second group included SOTRs with CMV viremia or disease, who underwent CMV CMI testing at time of CMV diagnosis and at various time points during antiviral treatment. These patients were prospectively followed for CMV relapse for 1 year post-primary CMV episode. Standard definitions were used to define CMV infection and disease. Results In the primary prophylaxis cohort, 24 CMV mismatched (D+/R-) SOTRs were enrolled. Only 1 patient (4.2%) demonstrated a CMV CMI >0.2 IU/mL by the end of prophylaxis; this patient did not develop CMV disease. Four (16.6%) patients developed post-prophylaxis CMV infection, none of which had CMV CMI >0.2 IU/ml. In the post-treatment cohort, 20 CMV viremic SOTRs were enrolled, including 12 D+/R- (60%). Eighteen (90%) had CMV CMI levels >0.2 IU/mL by end of treatment and none developed CMV relapse. In contrast, the single patient who relapsed after treatment had a CMV CMI response < 0.2 IU/ml (p=0.05). Conclusion CMV D+/R- SOTRs are unlikely to develop CMV CMI during valganciclovir prophylaxis. Thus, the utility of CMV CMI for risk stratification of post-prophylaxis CMV infection in CMV D+/R- SOTRs is questionable. Conversely, CMV CMI testing may potentially be a useful marker of CMV relapse risk after treatment and guide the role of secondary antiviral prophylaxis. Disclosures Elitza Theel, PhD, D(ABMM), Euroimmun US: Advisor/Consultant|Oxford Immunotech: Advisor/Consultant|Roche Diagnostics: Advisor/Consultant|Serimmune Inc: Advisor/Consultant Raymund R. Razonable, MD, American Society of Transplantation: Board Member|gilead: Grant/Research Support|novartis: DSMB|regeneron: Grant/Research Support|Roche: Grant/Research Support.

A viewpoint describing the American Society of Transplantation rationale to conduct a comprehensive patient survey assessing unmet immunosuppressive therapy needs.

This viewpoint aims to "set the stage" and provide the rationale for the proposed development of a large-scale, comprehensive survey assessing transplant patients' perceived unmet immunosuppressive therapy needs. Research in organ transplantation has historically focused on reducing the incidence and impact of rejection on allograft survival and minimizing or eliminating the need for chronic immunosuppressive therapies. There has been less emphasis and investment in therapies to improve patient-reported outcomes including health-related quality of life and side-effects. Patient-focused drug development (PFDD) is a new and important emphasis of the Food and Drug Administration (FDA) that provides a guiding philosophy for incorporating the patient experience into drug development and evaluation. The American Society of Transplantation (AST) Board of Directors commissioned this working group to prepare for the conduct of a comprehensive patient survey assessing unmet immunosuppressive therapy needs. This paper aims to describe the basis for why it is important to conduct this survey and briefly outline the plan for broad stakeholder engagement to ensure the information gained is diverse, inclusive, and relevant for advancing PFDD in organ transplant recipients.

Monkeypox a Concern for Donor-derived Infection?

Monkeypox a Concern for Donor-derived Infection?

Introduction of Dr Mannikam Suthanthiran as Recipient of the Medawar Prize for 2022.

Introduction of Dr Mannikam Suthanthiran as Recipient of the Medawar Prize for 2022.

Comorbidities Associated with Early Mortality after CD19 CAR-T Cell Therapy

Objective: CD19 chimeric antigen receptor (CAR) T-cell therapy has changed the standard for treatment of relapsed and/or refractory (r/r) large b-cell lymphoma (LBCL). Currently, pre-treatment evaluation of patients and disease factors do not accurately predict outcomes. This study aims to identify risk factors associated with early mortality prior to day 100 after CAR-T infusion. Methods: We performed a single-centered retrospective adult patients (pts) with r/r LBCL who received CAR-T cell therapy between 2018-2021. CAR-T cell toxicities graded according to either CAR T-Cell Therapy-Associated Toxicity (CARTOX) grading system prior to May, 2019 or American Society of Transplantation and Cellular Therapy (ASTCT) consensus grading thereafter for cytokine release syndrome (CRS) and immune cell associated neurotoxicity syndrome (ICANS). Comorbidities defined as per Hematopoietic Cell Transplantation-specific Comorbidity Index (HCT-CI). (Sorror et al., 2009). Hepatic dysfunction defined as infection with hepatitis B or C or history of liver cirrhosis or elevated total bilirubin, AST, or ALT on at least two values on two different days from day -24 till day -10 prior to CAR-T. Cardiovascular (CV) comorbidity determined by presence of coronary heart disease, congestive heart failure or reduced ejection fraction detected by echocardiogram. Psychiatric disturbance defined as presence of depression and/or anxiety requiring treatment or consultation. Patient demographics, disease characteristics and clinical outcomes summarized through descriptive statistics. Wilcoxon rank sum test used to evaluate difference in a continuous variable between patient groups. Kaplan-Meier method used to estimate time-to-event endpoints including progression free survival (PFS), and overall survival (OS). Results: Two hundred and fifty patients included in analysis. Median age of 61years (range: 18-89) and 30.8% of patients were female (n=77). Histology was categorized as LBCL (65.9%) and included diffuse LBCL or high grade LBCL, transformed follicular lymphoma (26.9%), primary mediastinal b-cell lymphoma (6.4%) or follicular lymphoma (0.8%). Majority of pts received axicabtagene ciloleucel 95.6% (n=239) while 4.4% (n=11) received tisagenlecleucel and 52% (n=130) of pts received bridging therapy. CRS of any grade was 90.4% ; ICANS any grade was 57.2% while grade 3 CRS/ICANS occurred 6.4% and 38.4% respectively. Median follow-up 24.7 months (mo) (95% CI: 20.7 ~ 26.4 mo). One-hundred twenty-eight pts died during follow-up, 48 pts died within 100 days, and most common cause of death was progression of lymphoma (29.2%; n=73). Early 30-day mortality occurred in 4.8% pts and causes of death due to CAR-T related toxicity in 6 pts, disease progression in 3 pts, and infection in 1 pts. 100-day mortality rate was 24.6% (n=32) for pts >60 years old vs 13.3% (n=16) for <60 (p-value=0.02). 100-day mortality rate was 36.5% for ECOG 2-4 vs 14.9% for ECOG 0-1 (p-value=0.0005). In terms of non-relapsed mortality (NRM), risk stratification according to cumulative HCT-CI score was not associated with higher 100-day NRM (p=0.24). Pts with cardiac score of 1 had a higher NRM (26.9% vs. 8.1%; p-value=0.005). The 100-day NRM rates for hepatic score of 0, 1, and 3 were 8.9%, 14.3%, and 50% (p-value=0.04). Pts with psychiatric disturbance score of 1 had higher 100-day NRM (19.6% vs. 7.8%; p-value=0.03). Conclusion: This single center retrospective study observed an increase in 100-day mortality in correlation with pre-treatment performance status, and older age. Pts with cardiac comorbidity, hepatic dysfunction or psychiatric disturbance had a higher 100-day NRM. Similar to other studies, the combined HCT-CI score was not predictive of NRM, but individual variables were associated with higher non-CART related toxicity. These findings require validation with further studies. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

ASHP Distinguished Leadership Award.

Marie A. Chisholm-Burns, PharmD, PhD, MPH, MBA, FCCP, FASHP, FAST, executive vice president and provost at Oregon Health and Science University in Portland, and Miriam A. Mobley Smith, PharmD, FASHP, interim dean of the University of Hawaii at Hilo Daniel K. Inouye College of Pharmacy, are the 2022 recipients of the ASHP Board of Directors Distinguished Leadership Award. The award recognizes contributions to excellence in pharmacy practice leadership in acute and ambulatory care settings. For nearly 30 years, Chisholm-Burns has embraced transformational learning opportunities that foster diverse and equitable academic and healthcare environments and encourage dialogue and innovation among students, patients, and providers. She seeks and supports opportunities to advance the success of students, faculty, staff, alumni, and other academic stakeholders. Her scholarly accomplishments include more than 380 publications and over $17 million in external funding as principal investigator or coinvestigator on research projects. She has served on governing boards of the Accreditation Council for Pharmacy Education, the American Society of Transplantation, the Georgia College Foundation, and the University of Tennessee Foundation.

Joining Forces in Basic Science: ITS Meeting 2.0.

The second International Transplant Science (ITS) meeting jointly organized by the European Society for Organ Transplantation (ESOT), the American Society of Transplantation (AST), and The Transplantation Society (TTS) took place in May 2022 in one of Europe’s most iconic cities: Berlin, Germany. The ITS meeting 2022 was designed to serve as an international platform for scientific discussions on the latest ground-breaking discoveries in the field, while providing an excellent opportunity to present cutting-edge research to the scientific community. We think this is fundamental for the exchange of new ideas and establishment of collaborative work between advanced transplant experts, young professionals and early-stage researchers and students. Scientific sessions tackled hot topics in transplantation such as mechanisms of tolerance, biomarkers, big data and artificial intelligence. Our educational pre-meeting focused on the breakthrough and challenges in single-cell multimodal omics. The program included panel discussions illuminating various topics concerning conflicts and problems related to gender, such as challenges for female scientists. Attendees returned to their institutes with not only profound knowledge of the latest discoveries, technologies, and concepts in basic and translational science, but also inspired and excited after discussions and networking sessions with fellow scientists which have been duly missed during the pandemic.

RE-AIMing the Focus on Health Equity in Surgery.

Comprehensive Transplant Institute, University of Alabama at Birmingham, Birmingham, AL Disclosures: R. Reed receives funding from the American Society of Transplantation. J. Locke receives funding from the National Institutes of Health and United Therapeutics. The author reports no conflicts of interest. [email protected].