American Society Of Transplantation Research Articles

244.10: Health System Barriers and Facilitators to Living Donor Kidney Transplantation: A Tale of Two States With the Highest and Lowest Rates

Purpose: Current efforts to increase living donor kidney transplantation (LDKT) entails identifying patient-level barriers and little is known about barriers that exist at the level of the health systems. The provision of transplantation in Canada is at the provincial level and there is wide variability in LDKT performance across different provinces. We aimed to learn and compare health systems with the best and the worst performance in LDKT, and to identify health system-level barriers to LDKT. Methods: This study took the form of a comparative case study analysis. Case study research is an in-depth and non-interventional examination of a single case over time using retrospective and contemporary data. Data collection entailed semi-structured interviews, document review, and participant observation. Data were analyzed thematically to generate themes surrounding the attributes and processes of a health system that facilitate the delivery of LDKT to patients, and those that create barriers. Results: In the best-performing province of Canada, five themes emerged as facilitators to the delivery of LDKT to patients. The relationship between two provincial organizations (a regional transplant and a regional nephrology order) was identified as key to enabling the mandate and processes for LDKT. On the other hand, in the worst-performing province, similar themes emerged as barriers to LDKT. Barriers were identified at the levels of organizational coordination, professional knowledge, resources, geography, and governance. Particularly, inconsistent coordination between regional clinics and transplant centers and poor role definition was seen to hinder and delay care processes. Conclusion: By comparing two health systems with variable rates of LDKT, we have identified several real-world health system-level barriers to the delivery of LDKT to patients. Many of these barriers are modifiable and have implications for practitioners, policymakers, administrators, and patients. This work is supported by a Gift of Life Institute Clinical Faculty Development Research Grant from the American Society of Transplantation and a Health Research Grant, Kidney Foundation of Canada.

Consensus recommendations for use of maintenance immunosuppression in solid organ transplantation: Endorsed by the American College of Clinical Pharmacy, American Society of Transplantation, and the International Society for Heart and Lung Transplantation

Advances in maintenance immunosuppression over the past three decades have improved solid organ transplantation outcomes dramatically. Uninterrupted access to immunosuppression is paramount to minimize rejection and maintain allograft and patient survival. There is no standardized approach to maintenance immunosuppression management. Agents used vary based on transplanted organ, center-specific protocol, provider expertise, insurance formularies, ability to cover co-pays, recipient characteristics and tolerability. Published data reflects this heterogeneity. Despite this limitation, maintenance immunosuppression usage cross pollinates between organ groups with standard of care agents often being used off-label, making medication access a challenge for many transplant recipients. A multidisciplinary panel of American transplant clinicians was formed to review published literature on maintenance immunosuppression with the goal to formulate consensus recommendations for their use in specific organ groups. These consensus recommendations are intended to provide transplant clinicians with a summary of literature on maintenance immunosuppression in the modern era and to support transplant team members working to secure medication access for patients.

Consensus recommendations for use of maintenance immunosuppression in solid organ transplantation: Endorsed by the American College of Clinical Pharmacy, American Society of Transplantation, and International Society for Heart and Lung Transplantation: An executive summary.

Advances in maintenance immunosuppression over the past three decades have improved solid organ transplantation outcomes dramatically. Uninterrupted access to immunosuppression is paramount to minimize rejection and maintain allograft and patient survival. Agents used vary based on transplanted organ, center-specific protocol, provider expertise, insurance formularies, ability to cover co-pays, recipient characteristics and tolerability. Published data reflects this heterogeneity. Despite these obstacles, the information about maintenance immunosuppression use cross pollinates between organ groups with standard of care agents often being used off-label, making medication access a challenge for many transplant recipients. A multidisciplinary panel of American transplant clinicians was formed to review published literature on maintenance immunosuppression with the goal to formulate consensus recommendations for their use in specific organ groups. These consensus recommendations are intended to provide transplant clinicians with a summary of literature on maintenance immunosuppression in the modern era, and to support transplant team members working to secure medication access for patients.

Prescribing Nirmatrelvir/Ritonavir for COVID-19 in Advanced CKD.

Prescribing Nirmatrelvir/Ritonavir for COVID-19 in Advanced CKD.

Health Care Transition for Adolescents and Young Adults With Pediatric-Onset Liver Disease and Transplantation: A Position Paper by the North American Society of Pediatric Gastroenterology, Hepatology, and Nutrition.

Advances in medical therapies and liver transplantation have resulted in a greater number of pediatric patients reaching young adulthood. However, there is an increased risk for medical complications and morbidity surrounding transfer from pediatric to adult hepatology and transplant services. Health care transition (HCT) is the process of moving from a child/family-centered model of care to an adult or patient-centered model of health care. Successful HCT requires a partnership between pediatric and adult providers across all disciplines resulting in a transition process that does not end at the time of transfer but continues throughout early adulthood. Joint consensus guidelines in collaboration with the American Society of Transplantation are presented to facilitate the adoption of a structured, multidisciplinary approach to transition planning utilizing The Six Core Elements of Health Care Transition TM for use by both pediatric and adult specialists. This paper provides guidance and seeks support for the implementation of an HCT program which spans across both pediatric and adult hepatology and transplant centers.

Stewardship of COVID-19 volunteers by nested trial design

Stewardship of COVID-19 volunteers by nested trial design

Common trajectories of highly effective CD19-specific CAR T cells identified by endogenous T cell receptor lineages

Abstract Current chimeric antigen receptor-modified (CAR) T cell therapy products are evaluated in bulk, without assessment of the possible heterogeneity in effector potential between cells. Conceivably, only a subset of the pre-infusion product differentiates into optimal effectors. We generated a comprehensive single-cell gene expression and T cell receptor (TCR) sequencing dataset using both pre- and post-infusion CD19-CAR T cells from peripheral blood and bone marrow of pediatric patients with B cell acute lymphoblastic leukemia (B-ALL). We identified potent effector post-infusion cells with identical TCRs to a subset of pre-infusion CAR T cells. Effector precursor CAR T cells exhibited a unique transcriptional profile compared to other pre-infusion cells, and the number of effector precursor cells infused correlated with peak CAR T cell expansion. Additionally, we identified an unexpected cell surface phenotype (TIGIT+, CD62Llo, CD27−), conventionally associated with inhibiting effective T cell responses, that we used to successfully enrich for subsequent effector potential. Collectively, these results demonstrate that highly diverse effector potentials are present among cells in pre-infusion cell products, which can be exploited for diagnostic and therapeutic applications. Furthermore, we provide an integrative experimental and analytical framework for elucidating the biological mechanisms underlying effector development in other CAR T cell therapy products. This work was supported by the National Institutes of Health (NIH)/National Cancer Institute grant P30CA021765, NIH grants U01AI150747 and R01AI136514 (PGT), the American Society of Transplantation and Cellular Therapy (AT), the American Society of Hematology (AT), the Key for a Cure Foundation (PGT), the Mark Foundation ASPIRE Award (PGT), and the American Lebanese Syrian Associated Charities (SG, PGT). Part of the laboratory studies were performed by the Center for Translational Immunology and Immunotherapy (CeTI2), which is supported by SJCRH. The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH.

Vaccination in pediatric solid organ transplant: A primer for the immunizing clinician.

Pediatric solid organ transplant (SOT) recipients are at a uniquely elevated risk for vaccine preventable illness (VPI) secondary to a multitude of factors including incomplete immunization at the time of transplant, inadequate response to vaccines with immunosuppression, waning antibody titers observed post-SOT, and uncertainty among providers on the correct immunization schedule to utilize post-SOT. Multiple guidelines are in existence from the Infectious Diseases Society of America and the American Society of Transplantation, which require use in adjunct with additional published references. We summarize the present state of SOT vaccine recommendations from relevant resources in tandem with the Centers for Disease Control and Prevention Advisory Committee on Immunization Practices guidance utilizing both routine and rapid catch-up schedules. The purpose of this all-inclusive review is to provide improved clarity on the most optimal pre- and post-transplant vaccine management within a one-stop-shop for the immunizing clinician.

1418. Single Center Treatment Patterns for Asymptomatic Bacteriuria and UTIs in Kidney Transplant Recipients: Are We Still Overtreating?

BackgroundIn February 2019, the American Society of Transplantation (AST) published guidelines on the management of asymptomatic bacteriuria (AB) and urinary tract infections (UTIs) in kidney transplant (KT) recipients. These recommendations include avoiding treatment of AB > 2 months post-transplant and outline the duration of treatment (DT) for uncomplicated and complicated UTIs. We reviewed management of these syndromes and guideline concordance at our institution.MethodsWe conducted a single-center, retrospective cohort study of KT recipients age > 18 years who underwent transplantation between June 2016 - June 2020. Patients were obtained through query of our electronic medical record for documented UTI syndromes and included if a diagnosis was confirmed between March 2019 - December 2020 upon chart review. Definitions of AB, complicated UTI, and uncomplicated UTI were based on AST definitions. Patients with AB < 2 months post-transplant were excluded. Outcomes included treatment of AB, DT, 30-day hospital admission and re-admission, and 30-day mortality. Bivariate analysis was conducted using chi square and t test. ResultsSeventy-four patients (mean age 55.4 years, 62.0% female) were included. Twenty-one patients had AB, 90% of whom received antibiotics. Distribution of diagnoses and median DT among those treated with antibiotics is outlined in Table 1. Overall DT was similar in patients whose care included infectious disease (ID) input and those who did not (10.0 vs. 10.0 days, p=0.12), although ID involvement was more common in complicated UTIs. There was no difference in 30-day admission rates for those receiving < 7 days vs. > 7 days of antibiotics (p=0.53) (Table 2) including those with complicated UTIs (5/15 in < 7 days (33%) vs. 4/18 in > 7 days (22%) p=0.49). There were no deaths within 30 days of diagnoses. ConclusionDespite guidelines, treatment of AB is common and uncomplicated UTIs often receive prolonged courses of antibiotics. There was no increased risk of admission or mortality with shorter DT, though these results should be interpreted cautiously given the small sample size. Greater stewardship efforts are needed in this high-risk population.Disclosures Kelsie Cowman, MPH, Merck (Research Grant or Support)

1379. Vaccination Rates among Liver Transplant Recipients at a Tertiary Care Hospital in Newark, NJ

BackgroundTransplant candidates and recipients are at increased risk of infectious complications of vaccine-preventable diseases due to their longstanding immunosuppressive regimens. We assessed the rates of vaccination in our liver transplant patients at University Hospital (UH) in Newark, NJ. MethodsRetrospective chart-review including patients > 18 years old who underwent liver transplantation at UH for a 3-year period from 01/01/2017 to 07/20/2020. Data collected included demographics, clinical outcomes, eligibility and receipt of vaccinations before and after transplantation, protection titers after administration of hepatitis vaccinations and presence of an ID outpatient consultation. We looked at the following receipt of vaccinations: Prevnar-13, Pneumovax-23, Influenza, TDaP, Shingrix, Varivax, Havrix and Engerix/Heplisav. Characteristics of study participants was analyzed using descriptive statistics and Chi-Square/Fisher’s Exact tests were used to test associations. Results119 unique medical charts were reviewed and no patients were excluded. Of those patients who were eligible to receive Hepatitis A vaccination, only 44.8% were documented to receive vaccination and of those eligible to receive Hepatitis B vaccination, only 47.8% received it. Influenza vaccination pre-transplantation was 46% and 66.1% in post-transplant recipients. For the other vaccinations, during the pre-transplant period, 17.6 % of patients received Prevnar-13, 36.1% Pneumovax-23 and 20.2% TDaP and 26.1% received Shingrix. Patients who had ID consultation were significantly more likely to receive appropriate Hepatitis A and Hepatitis B vaccinations (p values 0.026 and 0.005). ConclusionWe are not meeting national vaccination standards set by the American Society of Transplantation (AST) for optimal vaccination in this population. Our study can inform of possible solutions to increase vaccination rates in this population such as the simple addition of a smartphrase within EMR notes to remind providers to order appropriate vaccinations and eventually, a more long term solution of creation of a dedicated vaccination clinic and/or routine ID pre-transplant evaluations for all transplant candidates. Disclosures All Authors: No reported disclosures

Tisagenlecleucel Demonstrates Safety, Efficacy and CNS Trafficking in Primary CNS Lymphoma

Tisagenlecleucel Demonstrates Safety, Efficacy and CNS Trafficking in Primary CNS Lymphoma

Severe Cytokine Release Syndrome Associated with Worse Outcomes in Recipients of a Haploidentical Stem Cell Transplant

Introduction: The utilization of haploidentical (haplo) donors for allogeneic hematopoietic stem cell transplant (HCT) recipients has allowed more donor options to treat a multitude of hematopoietic malignancies and disorders. However, there are substantial complications and morbidities associated with haplo HCT. Cytokine release syndrome (CRS), a manifestation of alloreactive T cell expansion, has posed an obstacle early after stem cell infusion. CRS is well described among chimeric antigen receptor (CAR) T cell therapy recipients, where anti-interleukin (IL) 6 therapy and glucocorticoids to abrogate cytokine activity depends on objective physiologic markers and neurologic changes. In 2019, the American Society of Transplantation and Cellular Therapy (ASTCT) developed a consensus CRS grading scale for CAR T cell therapy that has since been widely adopted for these recipients (Lee et al, Biol Blood Marrow Transpl 2019). While the etiology of CRS differs between haplo HCT and CAR T cell recipients, severe CRS (grade 3 or 4) is seen in both patient populations, defined by ASTCT CRS grading as non-fluid responsive hypotension and/or capillary leak necessitating increased ventilatory support. We investigated whether the newly adopted ASTCT CRS grading could apply to a haplo HCT population in predicting overall survival (OS) and progression-free survival (PFS) at 1 year as well as the 2-year probability of graft-versus-host disease (GVHD).Methods: This IRB-approved retrospective analysis assessed 64 patients who underwent haplo HCT at Colorado Blood Cancer Institute from July 2015 to December 2018. All but one patient received peripheral blood-derived stem cells, and all patients received post-transplant cyclophosphamide, tacrolimus, and mycophenolate mofetil for GVHD prophylaxis. Variables of birth sex, primary disease, disease risk index (DRI), blood type, degree of HLA-mismatching, presence of donor-specific antibodies, Hematopoietic Cell Transplant Comorbidity Index (HCT-CI), conditioning regimen, and cell dose were assessed. In all patients, fever, blood pressure, and oxygen supplementation were used to identify the maximum CRS grade between 0-5 days after HCT using ASTCT CRS grading. Patients with other etiologies (i.e. infection, cardiomyopathy) were excluded from the analysis. CRS grading was then dichotomized to mild (CRS grades 0-2) or severe (grades 3-4), reflecting the physiologic changes that align with minimal compared to intensive cardiopulmonary support. As all patients had complete follow-up to 2 years, logistic regression was used to estimate association between severe CRS and outcome.Results: When adjusted for age, DRI and HCT-CI, development of severe CRS was associated with an inferior PFS at 1 year (odds ratio (OR) 0.22, (95% Confidence Interval (CI) 0.07, 0.69), p = 0.01). Inferior OS was also seen in those who developed severe CRS but the magnitude of the effect was smaller and not considered definitive (OR 0.38, (95%CI 0.13, 1.13), p=0.082). Increased non-relapse mortality (NRM) was also seen with severe CRS. Due to the low number of events, adjustment for only one factor at a time was necessary. When adjusted for age (OR 2.94, (95%CI 0.82, 11.1), p=0.101), DRI (OR 3.23, (95%CI 0.91, 11.1), p=0.069), HCT-CI (OR 2.94, (95%CI 0.85, 10), p=0.089), and conditioning regimen (OR 3.23, (95%CI 0.91, 11.1), p=0.071), consistent results were demonstrated, although not definitive. This was also observed with the risk of relapse, adjusted for conditioning regimen (OR 2.56, (95%CI 0.76, 9.09), p=0.126) and DRI (OR 2.56, (95%CI 0.75, 8.33), p=0.132). There was no demonstrable association between CRS and the probability of acute GVHD. However, severe CRS was associated with a reduction in the development of any chronic GVHD at 2 years (OR 0.24, (95%CI 0.08, 0.72), p=0.011).Conclusion: This analysis suggests that an adapted ASTCT CRS grading, dichotomizing into those with mild (grades 0-2) or severe (grades 3-4) CRS may identify haplo HCT recipients at risk for inferior outcomes. Haplo HCT recipients with severe CRS demonstrated an inferior PFS. The data also showed numerical decreases in overall survival, higher relapse, and higher NRM. On the other hand, severe CRS was associated with a decreased probability of chronic GVHD. As the analysis was limited to a single site, validation of adapted ASTCT grading in a larger haplo HCT population is necessary. DisclosuresNo relevant conflicts of interest to declare.

Evaluating patients with cancer history prior to solid organ transplantation : Consensus statement of the American Society of Transplantation

Evaluating patients with cancer history prior to solid organ transplantation : Consensus statement of the American Society of Transplantation

Getting the COVID-19 vaccine as a transplant patient

‘Yes! I am fully vaccinated’, I said to myself. The thrill, the excitement, coupled with too many other emotions to describe came swelling over me. I was also all alone,...

Transplant administration-A survey of the roles and responsibilities of kidney and pancreas medical directors of US transplant centers.

The current American Society of Transplantation (AST) accredited transplant fellowship programs in the United States provide no structured formal training in leadership and administration which is essential for successfully running a transplant program. We conducted a survey of medical directors of active adult kidney and kidney-pancreas transplant programs in the United States about their demographics, training pathways, and roles and responsibilities. The survey was emailed to 183 medical directors, and 123 (67.2%) completed the survey. A majority of respondents were older than 50years (61%), males (80%), and holding that position for more than 10years (47%). Only 51% of current medical directors had taken that position after completing a one-year transplant fellowship, and 58% took on the role with no prior administrative or leadership experience. The medical directors reported spending a median 50%-75% of time in clinical responsibilities, 25%-50% of time in administration, and 0%-25% time in research. The survey also captured various administrative roles of medical directors vis-à-vis other transplant leaders. The study, designed to be the starting point of an improvement initiative of the AST, provided important insight into the demographics, training pathways, roles and responsibilities, job satisfaction, education needs, and training gaps of current medical directors.

Leveraging the Coronavirus Disease 2019 Pandemic: Is It Time to Consider Incorporating Mobile Applications Into Standard Clinical Management of the Liver Transplantation Patient?

Over the past decade, major advancements in the development of mobile applications and telehealth monitoring systems have assisted healthcare professionals in the diagnosis and management of chronic disease. When effectively used, mobile applications can lead to higher quality care and better patient-reported outcomes.(1) Mobile applications can also improve patient self-management of chronic metabolic disease.(2) Despite these known benefits in other chronic diseases, telehealth and mobile applications have been slow to be adopted in standard clinical management of the liver transplant patient, in-part due to the complexity of chronic liver disease where there is often a need for physical examination, physical frailty assessment, support network determination and building rapport.(3).

The advisory Committee on Immunization practices' updated interim recommendation for allocation of COVID-19 vaccine-United states, December 2020.

This month’s MMWR selection is a link to the updated recommendations from the Advisory Committee on Immunization Practices regarding the allocation of COVID‐19 vaccine.

Practicing With Uncertainty: Kidney Transplantation During the COVID-19 Pandemic

The coronavirus disease 2019 (COVID-19) pandemic required transplant nephrologists, surgeons, and care teams to make decisions about the full spectrum of transplant program operations and clinical practices in the absence of experience or data. Initially, across the country, there was a reduction in kidney transplant procedures and a striking pause in the conduct of living donation and living-donor transplant surgeries. Aspects of candidate evaluation and follow-up rapidly converted to telehealth. Months into the pandemic, much has been learned from experiences worldwide, yet many questions remain. In this Perspective, we reflect on some of the practice decisions made by the transplant community in the initial response to the pandemic and consider lessons learned, including those related to the risks, benefits, and logistical considerations of proceeding with versus delaying deceased-donor transplantation, living donation, and living-donor transplantation during the pandemic. We review the evolution of therapeutic strategies for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and their use in transplant recipients, current consensus related to immunosuppression management in infected transplant recipients, and emerging information on vaccination against SARS-CoV-2. We share our thoughts on research priorities, discuss the areas in which we are still practicing with uncertainty, and look ahead to the next phase of the pandemic response.

Frailty and aging-associated syndromes in lung transplant candidates and recipients.

Many lung transplant candidates and recipients are older and frailer compared to previous eras. Older patients are at increased risk for pre- and posttransplant mortality, but this risk is not explained by numerical age alone. This manuscript represents the product of the American Society of Transplantation (AST) conference on frailty. Experts in the field reviewed the latest published research on assessment of elderly and frail lung transplant candidates. Physical frailty, often defined as slowness, weakness, low physical activity, shrinking, and exhaustion, and frailty evaluation is an important tool for evaluation of age-associated dysfunction. Another approach is assessment by cumulative deficits, and both types of frailty are common in lung transplant candidates. Frailty is associated with death or delisting before transplant, and may be associated with posttransplant mortality. Sarcopenia, cognitive dysfunction, depression, and nutrition are other important components for patient evaluation. Aging-associated inflammation, telomere dysfunction, and adaptive immune system senescence may also contribute to frailty. Developing tools for frailty assessment and interventions holds promise for improving patient outcomes before and after lung transplantation.

Navigating the COVID-19 pandemic: Initial impacts and responses of the Organ Procurement and Transplantation Network in the United States.

COVID‐19 has been sweeping the globe, hitting the United States particularly hard with a state of emergency declared on March 13, 2020. Transplant hospitals have taken various precautions to protect patients from potential exposure. OPTN donor, candidate, and transplant data were analyzed from January 5, 2020 to September 5, 2020. The number of new waiting list registrations decreased, with the Northeast seeing over a 50% decrease from the week of 3/8 versus the week of 4/5. The national transplant system saw near cessation of living donor transplantation (−90%) from the week of 3/8 to the week of 4/5. Similarly, deceased donor kidney transplant volume dropped from 367 to 202 (−45%), and other organs saw similar decreases: lung (−70%), heart (−43%), and liver (−37%). Deceased donors recovered dropped from 260 to 163 (−45%) from 3/8 compared to 4/5, including a 67% decrease for lungs recovered. The magnitude of this decrease varied by geographic area, with the largest percent change (−67%) in the Northeast. Despite the pandemic, discard rates across organ has remained stable. Although the COVID‐19 pandemic continues to evolve, OPTN data show recent evidence of stabilization, an indication that an early recovery of the number of living and deceased donors and transplants has ensued.