Evaluation Of Transplant Candidates Research Articles

Post-Transplantation Cyclophosphamide-Based Graft- versus-Host Disease Prophylaxis with Nonmyeloablative Conditioning for Blood or Marrow Transplantation for Myelofibrosis

We describe outcomes after post-transplantation cyclophosphamide and nonmyeloablative conditioning-based allogeneic blood or marrow transplantation for myelofibrosis using matched or mismatched related or unrelated donors. The conditioning regimen consisted of fludarabine, cyclophosphamide, and total body irradiation. Forty-two patients were included, with a median age of 63 years, of whom 19% had Dynamic International Prognostic Scoring System (DIPSS)-plus intermediate-1 risk, 60% had intermediate-2 risk, and 21% had high-risk disease, and 60% had at least 1 high-risk somatic mutation. More than 90% of patients engrafted neutrophils, at a median of 19.5 days, and 7% experienced graft failure. At 1 year and 3 years, respectively, overall survival was 65% and 60%, relapse-free survival was 65% and 31%, relapse was 5% and 40%, and nonrelapse mortality was 30% and 30%. Acute graft-versus-host disease grade 3-4 was seen in 17% of patients at 1 year, and chronic graft-versus-host disease requiring systemic therapy in occurred in 12% patients. Spleen size ≥17 cm or prior splenectomy was associated with inferior relapse-free survival (hazard ratio [HR], 3.50; 95% confidence interval [CI], 1.18 to 10.37; P=.02) and higher relapse rate (subdistribution HR [SDHR] not calculable; P=.01). Age >60 years (SDHR, 0.26; 95% CI, 0.08 to 0.80, P=.02) and receipt of peripheral blood grafts (SDHR, 0.34; 95% CI, 0.11 to 0.99; P=.05) were associated with a lower risk of relapse. In our limited sample, the presence of a high-risk mutation was not statistically significantly associated with an inferior outcome, although ASXL1 was suggestive of inferior survival (SDHR, 2.36; 95% CI, 0.85 to 6.6; P=.09). Overall, this approach shows outcomes comparable those of to previously reported approaches and underscores the importance of spleen size in the evaluation of transplantation candidates.

Evaluation and Management of Liver Transplant Candidates With Prior Nonhepatic Cancer: Guidelines From the ILTS/SETH Consensus Conference.

Liver transplant in patients with prior nonhepatic cancer is a matter of concern, needing further research, development, and consensus guidelines. This International Liver Transplantation Society/Sociedad Española De Trasplante Hepático consensus conference document focuses on the role of liver transplantation in patients with a prior history of nonhepatic cancer. This document addresses (1) the evaluation of transplant candidates with prior cancers based on the assessment of prognosis, the natural history of individual cancers, and the emerging role for circulating DNA and minimal residual disease in these patients; (2) the impact of prior treatments, including immunotherapy for prior malignancies; and (3) the surveillance of posttransplant cancer recurrence. The consensus statement is based on previously published guidelines, as well as a review of the current, relevant, published literature.

Understanding disparities and barriers associated with pediatric transplant evaluation and time to listing: Moving toward a more comprehensive picture.

Delayed time to listing (TTL) for pediatric transplant patients is associated with increased risks of mortality and morbidity. The full range of health disparities, sociodemographic factors, and other barriers associated with delays in listing in the pediatric transplant candidate evaluation process has not been fully examined. Retrospective chart reviews were conducted for 183 kidney, liver, and heart transplant candidates ages 0-18 who were referred for evaluation during 2012-2015. Demographic information and potential barriers (e g., social/medical factors, financial concerns) were gathered from pre-transplant evaluations and included in a comprehensive model to evaluate mechanisms that explain differences in TTL. Descriptive statistics, logistic regression models, Cox proportional hazards models, and path analysis were used for analyses. Candidates included 26.8% heart, 33.3% liver, and 39.9% kidney patients. The most common barrier to listing was financial (71.6%), followed by caregiver psychological or substance use (57.9%), and medical problems (49.7%). Higher age, kidney, and liver organ type (relative to the heart), and presence of social, medical, administrative/motivation, and financial barriers were all directly associated with longer TTL. Public insurance was indirectly associated with TTL through social, administrative/motivation, and financial barriers. Organ type was indirectly associated with TTL through financial barriers. Results suggest social problems, administrative issues, and financial issues act as mechanisms through which insurance type and liver transplant candidates face increased risk of delays in transplant listing time. There are numerous clinical implications and interventions that are warranted to reduce TTL among pediatric transplant candidates with co-occurring barriers.

A Cascade of Structural Barriers Contributing to Racial Kidney Transplant Inequities.

Stark racial disparities in access to and receipt of kidney transplantation, especially living donor and pre-emptive transplantation, have persisted despite decades of investigation and intervention. The causes of these disparities are complex, are inter-related, and result from a cascade of structural barriers to transplantation which disproportionately impact minoritized individuals and communities. Structural barriers contributing to racial transplant inequities have been acknowledged but are often not fully explored with regard to transplant equity. We describe longstanding racial disparities in transplantation, and we discuss contributing structural barriers which occur along the transplant pathway including pretransplant health care, evaluation, referral processes, and the evaluation of transplant candidates. We also consider the role of multilevel socio-contextual influences on these processes. We believe focused efforts which apply an equity lens to key transplant processes and systems are required to achieve greater structural competency and, ultimately, racial transplant equity.

Examining racial and socioeconomic disparity in the pediatric heart transplant evaluation.

Racial disparities have been reported among pediatric patients waitlisted for and undergoing heart transplantation but have not been studied further upstream in the transplant candidate evaluation process. We retrospectively studied our single-center experience in order to investigate any potential biases in the evaluation process. Results of the heart transplant evaluation in children ≤18years old at our institution were analyzed. Primary outcome was final disposition to waitlist or not. Race was defined by family self-identification. Descriptive and comparative statistical analyses were performed. From 2013 to 2019, 133 unique patients were referred for listing consideration. While Black patients comprised 44% of the referral population and had more markers of socioeconomic disadvantage, they comprised 43% of the patients who were listed for transplantation with no significant difference between these proportions (p=.96). Black and White patients made up a similar proportion of patients deemed too well or too ill for listing. Black patients had lower annual household income estimates and rates of household marriage. Despite identifying significant social challenges in 27 patients (18 of them Black), only five patients (3 Black and 2 White) were turned down for listing due to social barriers. While limited by the small number of patients turned down for social barriers, our transplant evaluation process does not appear to result in racial disparities in access to listing. Further studies are needed using national cohorts to explore possible racial disparities upstream from waitlisting and transplantation, such as during the referral and evaluation.

Evaluation of Transplant Candidates With a History of Nonadherence: An Opinion Piece.

The transparency and validity of assessing the candidacy of a patient for a solid organ transplant have recently been called into question by the media.1 Transplant centers perform a lengthy medical, surgical, and psychosocial evaluation on candidates with organ failure. This process ensures that there are no contraindications to surgery and to the use of long-term immunosuppressive medications. In addition, it helps ascertain if transplant candidates are likely to benefit from the transplant surgery over long term. Pretransplant nonadherence to prescribed therapy, medications, investigations, and clinical visits, is recognized as a relative or an absolute contraindication by transplant programs. For example, the Canadian Society of Transplantation states, given the use of immunosuppressive agents with a narrow therapeutic window, the impact of nonadherence to therapy on the risk of acute rejection and premature graft loss, and the scarcity of donor organs, nonadherence is a contraindication to kidney transplantation.2 This echoes the recommendations of some of the other major transplantation societies as summarized in Table 1.2-8 Most recommend delaying transplant surgery until patients have demonstrated adherence to therapy for 6 months. Table 1. Current Guidelines in the Assessment of Transplant Candidates With a History of Nonadherence.

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.

Evaluation and selection of the liver transplant candidate: updates on a dynamic and evolving process.

Although conceptually unchanged, the evaluation and selection of the liver transplant candidate has seen significant recent advances. Expanding criteria for transplant candidacy, improved diagnostics for risk stratification and advances in prognostic models have paralleled recent changes in allocation and distribution that require us to revisit core concepts of candidate evaluation and selection while recognizing its now dynamic and continuous nature. The liver transplant evaluation revolves around three interrelated themes: candidate selection, donor selection and transplant outcome. Introduction of dynamic frailty indices, bariatric surgery at the time of liver transplant in obese patients and improved therapies and prognostic tools for hepatobiliary malignancy have transformed candidate selection. Advances in hypothermic organ preservation have improved outcomes in marginal donor organs. Combined with expansion of hepatitis C virus positive and split donor organs, donor selection has become an integral part of candidate evaluation. In addition, with liver transplant for acute alcohol-related hepatitis now widely performed and increasing recognition of acute-on-chronic liver failure, selection of critically ill patients is refining tools to balance futility versus utility. Advances in liver transplant candidate evaluation continue to transform the evaluation process and require continued incorporation into our clinical practice amidst a dynamic backdrop of demographic and policy changes.

Psychological management of a patient before and after allograft of the face

In transplant specifications, a psychiatric and/or psychological opinion is requested before any intervention with pre- and post-operative psychological management. This transplant candidate evaluation must be based on two criteria: preparation for a heavy procedure and proper adherence to post-transplant anti-rejection treatments.

Impact of Pre-existing Comorbidities on Long-term Outcomes in Kidney Transplant Recipients

BackgroundOutcomes of patients with end-stage renal disease are mainly affected by their comorbidities. Detailed data evaluating the impact of pre-transplant comorbidities on long-term outcome after kidney transplantation are largely missing. MethodsIn a long-term retrospective analysis, we investigated 839 deceased donor kidney transplant recipients (KTRs) who received transplants between 1999 and 2014. The prevalence and impact of the most relevant comorbidities were studied in detail. ResultsAt the time of transplantation, 25% of KTRs had coronary artery disease (CAD), 16% had diabetes mellitus (DM), 11% had peripheral arterial disease (PAD), 8% had chronic heart failure (CHF), and 7% had cerebrovascular disease (CVD). KTRs with pre-existing CAD, DM, PAD, and CHF showed a significantly inferior patient survival. Multivariate analysis adjusting for all relevant factors and comorbidities confirmed CAD as most hazardous independent risk factor for premature death (hazard ratio [HR] 1.70; P = .002). A multivariate analysis revealed CHF and PAD as independent risk factors for death censored graft loss (HR 2.20; P = .003 and HR 1.80; P = .013). Diabetes was independently and significantly associated with T-cell- (HR 1.46; P = .020) and antibody-mediated rejections (HR 2.27; P = .030). ConclusionsDetailed quantification of the impact of pre-transplant comorbidities may facilitate the evaluation of transplant candidates, guide post-transplant follow-up, and may help to further refine prediction algorithms and allocation systems.

Acute heart failure after Orthotopic liver transplantation: a case series from one center

BackgroundPatients undergoing liver transplantation (LT) can develop acute heart failure (HF) in the postoperative period despite having had a normal cardiac evaluation prior to surgery. End-stage liver disease is often associated with underlying cardiac dysfunction which, while not identified during preoperative testing, manifests itself during or immediately after surgery.Case presentationWe describe three cases of non-ischemic acute HF developing shortly after LT in patients who had a normal preoperative cardiac evaluation. The challenges associated with both diagnosis and management of acute HF in the setting of a newly implanted graft will be discussed.ConclusionsDiastolic dysfunction, QTc interval prolongation, and an increase in BNP may be predictive of postoperative HF. Current recommendations for preoperative cardiovascular evaluation of transplant candidates does not include studies examining these risk factors and should be revised. Further investigations are necessary to evaluate these findings.

Should quality of the liver transplant candidate evaluation be measured?

Should quality of the liver transplant candidate evaluation be measured?

A commercial transplant network's perspective of value in solid organ transplantation: Strategizing for value in transplant care.

Solid organ transplantation has been an area of great interest to commercial payers ever since it moved into mainstream medical care beginning in the 1980s. Over the years a system of evaluating transplant program performance based on volume and one year graft and patient survival has developed. While this system has served its purpose, there is an increasing realization from payers that a need exists for a more sophisticated way to evaluate quality and cost-effectiveness of these complex procedures. We report on the perspective of a large transplant network and its efforts to better understand the drivers of value over the entire continuum of care from referral through one year post-transplant. We evaluated members of a large commercial health plan who were referred for solid organ transplantation between January 1, 2010 and April 30, 2014. A total of 18,453 cases were evaluated for both clinical and economic outcomes. We report on two areas that can impact value over the entire continuum of care. Large variation in clinical practice and cost was noted. The observed variation was independent of inclusion in the transplant network's preferred network. The average pre-transplant and post-transplant costs for kidney, liver and heart transplantation cases at center level showed a variation of between 18 and 250% of the network's average. Clinical outcomes of median days on the waitlist, waitlist mortality and readmission within thirty days after transplant also showed wide variation. There was similar wide variation in cardiac evaluation of transplant candidates despite the existence of published recommendations. We demonstrated that pre-emptive renal transplantation is a high value strategy for this membership independent of donor source. In the studied population the data show wide variation in both clinical and economic parameters related to the transplant process in programs with statistically similar one year patient and graft survival. These results require further examination. In this era of increased concern about delivering value in medical care we may need to reassess how we evaluate organ transplantation programs.

Evidence to Support a Contribution of Polyreactive Antibodies to HLA Serum Reactivity.

Assessing the serum reactivity to HLA is essential for the evaluation of transplant candidates and the follow-up of allograft recipients. In this study, we look for evidence at the clonal level that polyreactive antibodies cross-reactive to apoptotic cells and multiple autoantigens can also react to HLA and contribute to the overall serum reactivity. We immortalized B cell clones from the blood of 2 kidney transplant recipients and characterized their reactivity to self-antigens, apoptotic cells as well as native, denatured, and cryptic HLA determinants using enzyme-linked immunosorbent assay (ELISA), immunofluorescence, flow cytometry and Luminex assays. We also assessed the reactivity of 300 pretransplant serum specimens to HLA and apoptotic cells. We report here 4 distinct B cell clones cross-reactive to self and HLA class I. All 4 clones reacted to numerous HLA class I alleles but did not appear to target canonical "shared" epitopes. In parallel experiments, we observed a strong correlation between IgG reactivity to HLA and apoptotic cells in pretransplant serum samples collected from 300 kidney transplant recipients. Further analysis revealed that samples with higher reactivity to apoptotic cells displayed significantly higher class I percent panel-reactive antibodies compared to samples with low reactivity to apoptotic cells. We provide here (1) proof of principle at the clonal level that human polyreactive antibodies can cross-react to HLA, multiple self-antigens and apoptotic cells and (2) supportive evidence that polyreactive antibodies contribute to overall HLA reactivity in the serum of patients awaiting kidney transplant.

Lung transplantation: overall approach regarding its major aspects.

ABSTRACTLung transplantation is a well-established treatment for patients with advanced lung disease. The evaluation of a candidate for transplantation is a complex task and involves a multidisciplinary team that follows the patient beyond the postoperative period. Currently, the mean time on the waiting list for lung transplantation in the state of São Paulo, Brazil, is approximately 18 months. For Brazil as a whole, data from the Brazilian Organ Transplant Association show that, in 2014, there were 67 lung transplants and 204 patients on the waiting list for lung transplantation. Lung transplantation is most often indicated in cases of COPD, cystic fibrosis, interstitial lung disease, non-cystic fibrosis bronchiectasis, and pulmonary hypertension. This comprehensive review aimed to address the major aspects of lung transplantation: indications, contraindications, evaluation of transplant candidates, evaluation of donor candidates, management of transplant recipients, and major complications. To that end, we based our research on the International Society for Heart and Lung Transplantation guidelines and on the protocols used by our Lung Transplant Group in the city of São Paulo, Brazil.

Tumor DNA Index and α-Fetoprotein Level Define Outcome following Liver Transplantation for Advanced Hepatocellular Carcinoma

Background: Patients with hepatocellular carcinoma (HCC) beyond the Milan criteria are expected to have inferior outcome after liver transplantation (LT) and are therefore currently not considered for LT in many countries. The purpose of this study was to identify predictive factors for overall survival following LT for HCC that may support the Milan criteria in the selection of appropriate transplant candidates. Methods: Clinicopathological data on 364 patients with HCC who underwent LT between 1989 and 2010 were retrospectively evaluated. Predictors of overall survival in the entire cohort as well as in subsets of patients within (n = 214) and beyond (n = 150) the Milan criteria were analyzed. Results: Multivariate analysis in the entire cohort identified DNA index >1.5 (p < 0.0001), α-fetoprotein level (AFP) >200 ng/ml (p = 0.005), and HCC beyond the Milan criteria (p = 0.002) to be associated with worse overall survival. In patients within the Milan criteria (median survival: 170 months), DNA index >1.5 (p < 0.0001) was the only predictor of worse overall survival in multivariate analysis. In patients beyond the Milan criteria (median survival: 44 months), DNA index >1.5, AFP >200 ng/ml, microvascular invasion, patient age >60 years, and DNA index >1.5 concomitant with AFP >200 ng/ml were associated with worse overall survival in univariate analysis. Multivariate analysis identified DNA index >1.5 concomitant with AFP >200 ng/ml (p < 0.0001) as the only independent predictor of worse overall survival. Consequently, patients beyond the Milan criteria with a combined favorable DNA index ≤1.5 and AFP ≤200 ng/ml had a median survival (147 months) comparable to that of patients within the Milan criteria. Conclusions: DNA index and AFP level predict overall survival following LT in patients with advanced HCC beyond the Milan criteria. A combined assessment of these markers during the evaluation of transplant candidates can contribute to the selection of patients with HCC who may benefit from LT independently of their tumor burden.

Psychological criteria for contraindication in lung transplant candidates: a five-year study.

Lung transplantation presents a wide range of challenges for multidisciplinary teams that manage the care of the recipients. Transplant teams should perform a thorough evaluation of transplant candidates, in order to ensure the best possible post-transplant outcomes. That is especially true for the psychologist, because psychological issues can arise at any point during the perioperative period. The objective of our study was to evaluate the psychological causes of contraindication to waiting list inclusion in a referral program for lung transplantation. We retrospectively analyzed data on psychological issues presented by lung transplant candidates, in order to understand these matters in our population and to reflect upon ways to improve the selection process.

Liver and Pancreas Transplantation

More than 6,000 liver transplantations are performed annually in the United States. Enhancements in patient selection and surgical technique and the availability of more powerful immunosuppressive agents have resulted in steady improvement in patient survival. As a result, liver transplantation has been accepted as the standard of care for patients with severe acute or chronic liver disease in whom conventional modalities of therapy have failed. The major obstacle to patients receiving the procedure is the critical shortage of donor organs. Many more recipients of liver transplantation are now receiving the bulk of their care from general internists, gastroenterologists, and primary care physicians. As a result, recognition of potential long-term complications and the need for appropriate immunizations and regular screening visits have become increasingly important. This chapter discusses who qualifies as a candidate for liver transplantation, contraindications to transplantation, timing of transplantation, operative procedures, complications of transplantation (e.g., perioperative and surgical complications, immunologic complications, infectious complications, complications of medical and immunosuppressive therapy, and disease-specific complications), and transplantation outcome. Pancreas transplantation, which aims at providing physiologic insulin replacement, is a therapy that reliably achieves euglycemia in patients with type 1 diabetes mellitus. The discussion of pancreas transplantation focuses on topics such as evaluation of candidates for transplantation (including islet transplantation); contraindications to transplantation; operative procedures; outcome survival; and the effect of transplantation on disorders associated with type 1 diabetes mellitus. The figures show estimated 3-month survival as a function of the Model for End-Stage Liver Disease (MELD) score, the sections of the liver that can be used for transplantation, an algorithm for evaluation of patients with type 1 diabetes mellitus being considered for pancreas transplantation, and an illustration of enteric drainage technique used in whole pancreas transplantation. The tables provide the common indications for liver transplantation, the scoring system for the Child-Turcotte-Pugh classification of liver disease severity, drug interactions with immunosuppressants, and immunization recommendations for liver transplant patients. This chapter contains 4 highly rendered figures, 4 tables, 101 references, 5 MCQs, and 1 teaching slide set.

Liver and Pancreas Transplantation

More than 6,000 liver transplantations are performed annually in the United States. Enhancements in patient selection and surgical technique and the availability of more powerful immunosuppressive agents have resulted in steady improvement in patient survival. As a result, liver transplantation has been accepted as the standard of care for patients with severe acute or chronic liver disease in whom conventional modalities of therapy have failed. The major obstacle to patients receiving the procedure is the critical shortage of donor organs. Many more recipients of liver transplantation are now receiving the bulk of their care from general internists, gastroenterologists, and primary care physicians. As a result, recognition of potential long-term complications and the need for appropriate immunizations and regular screening visits have become increasingly important. This chapter discusses who qualifies as a candidate for liver transplantation, contraindications to transplantation, timing of transplantation, operative procedures, complications of transplantation (e.g., perioperative and surgical complications, immunologic complications, infectious complications, complications of medical and immunosuppressive therapy, and disease-specific complications), and transplantation outcome. Pancreas transplantation, which aims at providing physiologic insulin replacement, is a therapy that reliably achieves euglycemia in patients with type 1 diabetes mellitus. The discussion of pancreas transplantation focuses on topics such as evaluation of candidates for transplantation (including islet transplantation); contraindications to transplantation; operative procedures; outcome survival; and the effect of transplantation on disorders associated with type 1 diabetes mellitus. The figures show estimated 3-month survival as a function of the Model for End-Stage Liver Disease (MELD) score, the sections of the liver that can be used for transplantation, an algorithm for evaluation of patients with type 1 diabetes mellitus being considered for pancreas transplantation, and an illustration of enteric drainage technique used in whole pancreas transplantation. The tables provide the common indications for liver transplantation, the scoring system for the Child-Turcotte-Pugh classification of liver disease severity, drug interactions with immunosuppressants, and immunization recommendations for liver transplant patients. This chapter contains 4 figures, 4 tables, 101 references, 5 Board-styled MCQs, and 1 Teaching Slide Set.