Combined Organ Transplantation Research Articles

Pulmonary, Hepatic, and Allogeneic Hematopoietic Stem Cell Transplantation in Patients with Telomere Biology Disorders.

This study aimed to summarize evidence and provide consensus-based guidelines for management of transplantation in patients with telomere biology disorders (TBD). Specifically, this review focuses on clinical management of lung, liver, and bone marrow transplantation in TBD patients. TBD patients have specific unique biological vulnerabilities such as T cell immunodeficiency, susceptibility to infections, hypersensitivity to chemotherapy and radiation, and cytopenias. Furthermore, multiple organ involvement at diagnosis makes clinical management especially challenging due to higher degree of organ damage, and stress-induced telomeric crisis. Sequential and combined organ transplants, development of novel radiation and alkylator-free conditioning regimen, and use of novel drugs for graft-versus-host disease prophylaxis are some of the recent updates in the field. Multidisciplinary management is essential to optimize transplant outcomes in patients with TBD. In this review, we provide consensus-based transplant management guidelines for clinical management of transplant in TBD.

Axillary mechanical circulatory support improves renal function prior to heart transplantation in patients with chronic kidney disease

Impaired kidney function is often associated with acute decompensation of chronic heart failure and portends a poor prognosis. Unfortunately, current data have demonstrated worse survival in patients with acute kidney injury than in patients with chronic kidney disease during durable LVAD placement as bridge therapy. Furthermore, end-stage heart failure patients undergoing combined heart-kidney transplantation have poorer short- and long-term survival than heart transplants alone. We evaluated the kidney function recovery in our heart failure population awaiting heart transplantation at our institution, supported by temporary Mechanical Circulatory Support (tMCS) with Impella 5.5. The protocol (#22004000) was approved by the Mayo Clinic institutional review board, after which we performed a retrospective review of all patients with acute on chronic heart failure and kidney disease in patients considered for only heart and kidney combined organ transplant and supported by tMCS between January 2020 and February 2021. Hemodynamic and kidney function trends were recorded and analyzed before and after tMCS placement and transplantation. After placement of tMCS, we observed a trend towards improvement in creatinine, Fick cardiac index, mixed venous saturation, and glomerular filtration rate (GFR), which persisted through transplantation and discharge. The average duration of support with tMCS was 16.5 days before organ transplantation. The median pre-tMCS creatinine was 2.1 mg/dL (IQR 1.75–2.3). Median hematocrit at the time of tMCS placement was 32% (IQR 32–34), and the median estimated glomerular filtration rate was 34 mL/min/BSA (34–40). The median GFR improved to 44 mL/min/BSA (IQR 45–51), and serum creatinine improved to 1.5 mg/dL (1.5–1.8) after tMCS. Median discharge creatinine was 1.1 mg/dL (1.19–1.25) with a GFR of 72 (65–74). None of these six patients supported with tMCS required renal replacement therapy after heart transplantation. Early adoption of Impella 5.5 in this patient population resulted in renal recovery without needing renal replacement therapies or dual organ transplantation and should be further evaluated.

Implementation of a vaccination clinic for adult solid organ transplant candidates: A single-center experience

Vaccination is an evidence-based strategy to prevent or reduce the severity of infectious diseases (ID). Here, we aimed to describe the experience of implementing a vaccination clinic specifically targeting liver, heart, lung, and combined dual organ transplantation at a single transplantation center in Denmark. In this cohort of 242 solid organ transplant (SOT) candidates, we investigated seroprotection and the proportion of recommended vaccinations documented before transplantation. Furthermore, we registered completed vaccinations after ID consultations. The median age in our cohort was 53 years (IQR, 42–60), 60% were males (n = 135), and liver transplants (n = 138; 57%) were the most frequently planned organ transplants. Before the consultation to the vaccination clinic, influenza and pneumococcal vaccines had the highest proportion of documented vaccination (58% and 37%, respectively). Serological protection was more frequently observed for measles, mumps, or rubella (MMR, approximately 90% for each), while only 30% (n = 72) of SOT candidates showed seroprotection against pneumococcal disease. All SOT candidates required at least one of the recommended vaccines, and over 90% required three or more. At least 10% of patients in our cohort needed a live attenuated vaccine for either MMR or yellow fever. The most frequently administered vaccine was the tetanus–diphtheria-acelullar pertussis (Tdap) booster (n = 217; 90%), influenza vaccination was either administered (n = 16; 7%) or recommended (n = 226; 93%), PCV13 was administered (n = 155; 64%) or recommended (n = 27; 11%), and PPSV23 was either administered (n = 18; 7.4%) or recommended (n = 140; 58%). All SOT candidates adhered completely to their vaccination schedules. Based on our findings, we recommend prioritizing vaccination before transplantation by providing ID consultations for SOT candidates.

The Enigma of Heart-kidney Transplantation.

The Enigma of Heart-kidney Transplantation.

2103. Comparison of Antibiograms Across Solid Organ Transplant Services Within a Medical Center

Abstract Background Antibiograms summarize localized antimicrobial susceptibilities and are used to guide empiric antibiotic therapy. Antibiograms for subpopulations may offer more meaningful clinical data, especially in immunocompromised hosts who may be at higher risk for multidrug-resistant organisms. However, population-specific antibiograms are uncommon. The purpose of this study is to evaluate whether service-specific antibiograms provide more useful information than hospital-wide antibiograms. Methods This is a retrospective, single-center study that included bacterial isolates from all body sites collected between 2017-2020. Antibiograms were created in accordance with the Clinical and Laboratory Standards Institute guidelines, with susceptibilities reported as a percentage and a 95% confidence interval. A combined solid organ transplant (SOT) antibiogram and individual antibiograms based on the transplanted organ (heart, lung, liver, and kidney) were compared to a hospital antibiogram with a difference of ≥ 10% considered clinically significant. Results In the combined SOT antibiogram, Escherichia coli, Klebsiella aerogenes, and Klebsiella pneumoniae susceptibilities were lower for antibiotics such as ceftriaxone, ceftazidime, and ciprofloxacin compared to the hospital antibiogram. Overall susceptibilities for Pseudomonas aeruginosa in the SOT antibiogram were comparable to that of the hospital antibiogram; however piperacillin-tazobactam susceptibilities were substantially lower among lung and heart transplant patients. Among Staphylococcus aureus isolates, clindamycin susceptibilities were similar between the SOT antibiogram and hospital antibiogram. This was a result of lower susceptibilities among lung transplant patients, offset by greater susceptibility in liver, kidney, and heart transplant patients. Conclusion Clinically significant differences were seen in susceptibilities for several antibiotics against gram-negative and gram-positive pathogens in various transplant antibiograms. The combined SOT antibiogram minimized substantial between-service differences. Through population-specific antibiograms, providers may be able to improve empiric antibiotic therapy selection for their patient population. Disclosures Conan MacDougall, PharmD, MAS, Merck: Advisor/Consultant.

Transplantation of Hematopoietic Stem and Progenitor Cells from Cadaveric Organ Donors Leads to Long-Term Multilineage Engraftment in NSG Mice

Background Infusion of Hematopoietic Stem and Progenitor Cells (HSPC) from cadaveric organ donors (CD) has been used anecdotally in the setting of allogeneic Hematopoietic Stem Cell transplants (HSCT) most commonly with the intention for induction of mixed hematopoietic chimerism and subsequent immunological tolerance. No systematic study has addressed the functional capacity of these cells for inducing long-term multi-lineage engraftment. Since the introduction of post-transplant Cyclophosphamide (PTCy) it has been possible to reliably overcome HLA barriers and achieve stable engraftment across extensively HLA-mismatched donor and recipient pairs. Banked HSPC from cadaveric donors may provide a new approach to expand the number of donors for HSCT. Usage of HSPC from bone marrow (BM) of banked cadaveric donors is viewed as no different than live donor aspirated marrow by the FDA but is not yet available on the registry. This emerging source could be of high importance to allow rapid on-demand access to transplants for patients who lack HSPC donors or induce stable mixed chimerism and immune tolerance in patients undergoing combined organ and BM transplantation. The objective of our studies was to investigate whether hCD34⁺HSC selected from cadaveric BM retain their capacity for long-term multi-lineage engraftment. Methods and Results We compared CD34⁺-selected HSPC obtained from CD and living donors (LD) regarding their in vitro and in vivo function and with particular focus on their ability to achieve long-term multi-lineage engraftment following transplantation into NSG mice. Bone marrow was recovered from vertebral bodies of CD and CD34⁺ selected. 5x10⁵ hCD34⁺ cells from 24 different CD were transplanted i.v. in to NSG or SGM3 mice (n=5 per donor) following 1Gy total body irradiation (TBI). Blood was drawn every two weeks, starting week 4 and human CD45⁺ chimerism was analyzed via flow cytometry. All donors engrafted successfully and robust long-term multi-lineage engraftment >16 weeks was seen in 19 out of 22 donors. To further investigate the long-term repopulating capacity, we performed secondary transplants. BM of 15 primary engrafted donors was harvested, hCD45⁺ were selected with immunobeads and transplanted into 1Gy irradiated NSG mice. Successful multi-lineage engraftment after secondary transfer was observed in 12 out of 15 donors in the peripheral blood (PB). Results of tissue engraftment are still outstanding for most experiments. So far they showed mean engraftment of human CD45⁺ cells of 6.16%+/-2.4% for donor 1 and 8.48%+/-0.74% for donor 2 in the BM. To compare CD and LD we set up two side-by-side transplantation experiments and intra-mouse competitive engraftment studies using HLA-mismatched donors. Using side-by-side experiments no significant difference in human CD45⁺ chimerism was detected in blood measured at weeks 6, 12 and 16 pos-transplant. The tissues showed a mean engraftment of human CD45⁺ cells of 87% +/- 9.6% vs 71% +/- 9.5% in spleen and 76% +/- 5.3% vs 78% +/- 4% (NS) in BM upon takedown 20 weeks post-transplant. For our competitive assays, we transplanted 2.5x10⁵ hCD34⁺ i.v. from LD and CD simultaneously into NSG mice (n=5 per donor pair) following 1Gy TBI. In total 8 CD and 3 LD were used, out of whom 4 CD reached higher engraftment than the LD. Conclusion Our data suggest that CD34+HSPC from CD retain their long-term multi-lineage engraftment capacity, reaching at least equipotent levels as HSPC from living donors. Based on our findings cadaveric bone marrow should be considered as HSPC source for HSCT.

Comparison of Intensive Insulin Versus Oral Regimens on Early Glycemic Control Following Kidney Transplant.

Introduction: Insulin is commonly prescribed to manage early post-kidney transplant hyperglycemia due to its flexibility. Studies comparing the effectiveness of oral therapies on glycemic outcomes remain limited. Project aims: The purpose of this program evaluation was to analyze our experience using oral antiglycemic agents immediately post-kidney transplant, compared to patients managed with insulin monotherapy. Design: This was a single-center, retrospective review of adult kidney transplant recipients with new or worsening hyperglycemia between 01/2014-05/2020. Patients were excluded if they had a prior or combined organ transplant, type 1 diabetes, or were previously on intensive insulin. Patients discharged on oral medications were 1:1 matched to patients receiving intensive insulin based on pre-specified clinical parameters. The primary endpoint was the number of diabetes-related readmissions within 6-months of transplant. Key secondary endpoints included mean serum glucose and hemoglobin A1c levels. Results: Thirty patients prescribed oral therapies were successfully matched to patients receiving intensive insulin. Baseline characteristics were similar between groups, except for more whites in the insulin group. There were no differences in diabetes-related (6.7% vs 3.3%; P = 1.00) or all-cause readmissions within 6-months. Mean serum glucose (P = .99) and hemoglobin A1c (P = .49) levels were also similar between patients receiving oral agents and insulin. However, 7 patients in the oral group were eventually converted to standing insulin. Conclusion: Our experience suggested that the early use of oral antiglycemics post-kidney transplant in select patients can result in similar outcomes relative to insulin. Meticulous follow-up is necessary as one-quarter of patients may require conversion to insulin within 1-month.

How to Assess EVLP Lungs in Standard Clinical Use?

<h3>Purpose</h3> Ex-vivo lung perfusion (EVLP) is currently considered a valuable option to preserve, reassess or recondition pulmonary grafts prior to lung transplantation (LTx). Both standard and extended criteria donors lungs have been studied in clinical trials. Usually, a 20% deterioration of physiological parameters during EVLP is considered detrimental for the graft and a reason to decline it. In this study, we report the relation between EVLP parameters and primary graft dysfunction (PGD) in a clinical LTx program. <h3>Methods</h3> In our center the TransMedics OCS^TM Lung device is used. The indication for EVLP was combined organ transplantation, graft re-assessment or prolonged preservation based on an institutional algorithm and available resources. Standard clinical EVLP parameters (mean pulmonary artery pressure (PAP), vascular resistance (VR) and driving airway pressure(DAP)) were compared between the first and final assessment. The % difference (Δ) between these time points was calculated. Graft outcome was expressed as presence of any PGD grade 3 (PGD 3) within 72 hours. Statistical analysis was performed using student T-test comparing patients with PGD 3 vs. without. Combined organ (liver-LTx) and LTx cases were analyzed separately as well as together. <h3>Results</h3> Data are presented in figure 1. In total, 12 lungs were included. Overall, all grafts met acceptance criteria during EVLP and were transplanted. Despite this, 58% of the patients developed PGD 3. No statistically significant difference in EVLP parameters was observed between patients who developed and did not develop PGD 3. <h3>Conclusion</h3> Overall, the clinical EVLP parameters were within the limits of acceptance and even improved over time. Despite this, we observed a high incidence of PGD 3. At this moment it is not clear how to assess EVLP lungs in clinical use and predict the outcome after LTx. The role of EVLP in post-reperfusion injury requires further research.

Incidence, Risk Factors, and Outcomes of Stroke Following Cardiac Transplantation

Less is known about the risk factors and outcomes associated with stroke in the current era of increasing heart transplantation (HT) being performed in older patients. The impact of immunosuppression on risk of stroke has not yet been previously studied. We aimed to determine the incidence, risk factors and outcomes of stroke after HT. We retrospectively analyzed the incidence of ischemic and hemorrhagic strokes and associated outcomes in all consecutive HT recipients transplanted between 1994 and 2016 at a single institution. Of 529 patients who underwent HT, 57 (10.7%) developed stroke, 8.1% had an ischemic events and (2.6%) had a hemorrhagic stroke. Age at HT (adjusted hazard ratio [HR] 1.33; P=0.03) and diabetes (HR, 2.60; P=0.02) were associated with increased risk of ischemic events. Patients with stroke (any type) were more likely to have worse kidney function (HR, 1.81; P=0.02) whereas patients with ischemic events were more likely to undergo combined organ transplantation (HR, 2.01; P=0.05). Cytomegalovirus infection was found to be associated with increased risk of any stroke (HR, 2.09; P=0.02).Conversion from calcineurin inhibitor to sirolimus-based immunosuppression was not found to be associated with a significant change in stroke risk (HR, 1.39; P=0. 45) compared with calcineurin inhibitor maintenance therapy. Stroke of any type and ischemic events were independently associated with increased risk of death (HR, 1.90; P=0.001 and HR, 2.14; P<0.001, respectively). Stroke after HT is associated with increased mortality. Older age at HT, diabetes, renal dysfunction, and CMV infection were associated with greater risk of stroke.

Simultaneous right-sided nephrectomy with orthotopic liver and kidney transplantation\u2014An alternative method for patients with autosomal dominant polycystic liver and kidney disease

PurposeIn patients suffering from autosomal dominant polycystic liver and kidney disease (ADPLKD), combined organ transplantation often poses a technical challenge due to the large volume of both organs. To simplify the transplantation procedure by improving the exposure of anatomical structures, we introduce a novel surgical technique of orthotopic liver and kidney transplantation.MethodsThe modified simultaneous liver and kidney transplantation technique via a right-sided L-incision included three steps: (1) right-sided nephrectomy in the recipient followed by (2) orthotopic liver transplantation in cava replacement technique and (3) the orthotopic kidney transplantation with arterial reconstruction to the right common iliac artery.ResultsIn total, seven patients with ADPLKD were transplanted by using the modified transplantation technique. The mean operation time was 342.43 min (±68.77). Postoperative patients were treated for 6.28 days (±2.50) in the intensive care unit and were discharged from the surgical ward approximately 28 days (±5.66) after the operation with normal graft function. Complications associated with the use of the modified technique, such as bleeding, anastomotic stenosis, biloma, or urinoma, did not occur.ConclusionModified simultaneous liver and kidney transplantation is a safe alternative for patients with ADPLKD. By combining right-sided nephrectomy and orthotopic graft transplantation, the approach optimizes the exposure of anatomical structures and simplifies the transplantation procedure. Additionally, the modified transplantation technique does not require a particular organ explantation procedure and can be applied for all liver and kidney grafts.

Bracing for the Next Wave on the Long Haul: Lung Transplantation for Post-COVID-19 Respiratory Failure.

Bracing for the Next Wave on the Long Haul: Lung Transplantation for Post-COVID-19 Respiratory Failure.

Serum creatinine level at 1-month posttransplant can independently predict long-term graft survival and functional status.

BackgroundAfter the year 2000, kidney transplants with high immunologic risk and deceased donors increased rapidly in Korea. At the same time, the medical community developed special pretransplant and early posttransplantation management protocols. Our team evaluated the effect of early graft stabilization on long-term graft survival and functional status using databases from a high-volume kidney transplantation center.MethodsWe included 1,895 kidney transplant patients from a total of 1,976 performed between 2005 and 2018. Early graft failure within 1 month (n=9), loss to follow-up (n=2), pediatric recipient or donor (n=37), and combined organ transplantation (n=33) cases were excluded. We grouped the cases at 1-month posttransplantation by serum creatinine quantiles (1.0 mg%, 1.23 mg%, and 1.52 mg%).ResultsAfter an average of 95 months of follow-up (maximum 189 months), the high-serum creatinine group (4th quantile) showed significantly poorer graft survival than other groups (1st to 3rd quantile) (P<0.05). In multiple Cox regression analysis, a high serum creatinine level (4th quantile) at 1-month posttransplant is an independent risk factor for graft failure with a hazard ratio of 1.799 (P=0.013). The quantile group by serum creatinine shows a persistent, significant difference of functional graft status (glomerular filtration rate by Modification of Diet in Renal Disease method) among quantile groups beyond ten years posttransplant.ConclusionsSerum creatinine level at 1-month posttransplant is a strong independent predictor of graft survival and functional graft status beyond ten years posttransplant.

Combined Sequential Heart-Liver Transplantation

Many single ventricle patients palliated with the Fontan operation suffer from Fontan failure and progressive liver disease. Combined heart-liver transplantation is a rarely utilized and complex transplant strategy available for select Fontan patients. At the Hospital of the University of Pennsylvania, all Fontan patients deemed eligible for a heart transplantation undergo a combined sequential dual organ transplantation with same-donor organs. This article describes the techniques utilized as well as current results.

Ethical decision-making in simultaneous heart-liver transplantation.

Simultaneous heart-liver (SHL) transplants are only a small proportion of overall heart and liver transplantation, they have been increasing in frequency and thus challenge the equitable allocation of organs. The incidence of SHL transplants is reviewed along with the outcomes of SHL transplants and their impact on the waitlist, particularly in the context of solitary heart and liver transplantation. The ethical implications, most importantly the principles of utility and equity, of SHL transplant are addressed. In the context of utility, the distinction of a transplant being life-saving versus life-enhancing is investigated. The risk of hepatic decompensation for those awaiting both solitary and combined organ transplantation is an important consideration for the principle of equity. Lastly, the lack of standardization of programmatic approaches to SHL transplant candidates, the national approach to allocation, and the criteria by which programs are evaluated are reviewed. As with all multiorgan transplantation, SHL transplantation raises ethical issues of utility and equity. Given the unique patient population, good outcomes, lack of alternatives, and overall small numbers, we feel there is continued ethical justification for SHL, but a more standardized nationwide approach to the evaluation, listing, and allocation of organs is warranted.

Protein Intake, Fatigue and Quality of Life in Stable Outpatient Kidney Transplant Recipients.

Fatigue is a frequent complaint in kidney transplant recipients (KTR), often accompanied by poor quality of life (QoL). The role of nutrition as determinant of fatigue in KTR is largely unexplored. The aims of this study are to examine the association of protein intake with fatigue and QoL in KTR and to identify other determinants of fatigue. This cross-sectional study is part of the TransplantLines Cohort and Biobank Study (NCT03272841). Protein intake was calculated from urinary urea nitrogen (UUN) in 24-h urine samples. Fatigue was assessed by the Checklist Individual Strength (CIS) questionnaire; moderate and severe fatigue were defined as a CIS score of 20–34 and ≥ 35, respectively. QoL was assessed with the RAND-36-Item Health Survey (RAND-36). Associations of protein intake with fatigue and QoL were analyzed using multinomial logistic and linear regression analyses. We included 730 stable outpatient KTR (median age 58 year [IQR 48–65], 57% male) with a mean protein intake of 82.2 ± 21.3 g/d. Moderate and severe fatigue were present in 254 (35%) and 245 (34%) of KTR. Higher protein intake was significantly associated with lower risk of moderate fatigue (OR 0.89 per 10 g/d; 95%CI 0.83–0.98, p = 0.01), severe fatigue (OR 0.85; 95%CI 0.78–0.92, p < 0.001) and was associated with higher physical component summary score of QoL (β 0.74 per 10 g/d; 95%CI 0.39–1.09, p < 0.001). Higher BMI, a history of dialysis, glomerulonephritis as primary kidney disease and a history of combined organ transplantation were also associated with severe fatigue. In conclusion, amongst the potential modifiable factors of fatigue, higher protein intake is independently associated with lower risk of moderate and severe fatigue and with better QoL in KTR. These findings underline the need to incorporate nutritional assessment in the diagnostic work-up of fatigue. Intervention studies are needed to assess the benefits and safety of higher protein intake in KTR.

Characteristics and Outcomes of Patients Undergoing Combined Organ Transplantation (from the United Network for Organ Sharing)

Studies have shown that highly selected patients who underwent combined heart-kidney (HK) and heart-liver transplants (HLv) have short- and long-term outcomes comparable to those observed in primary heart transplantation (HT). Adults patients with stage D heart failure that underwent combined HK, HLv, and heart-lung (HL) were identified in the United Network for Organ Sharing registry from 1991 to 2016, with follow-up through March 2018. We conducted inverse probability of treatment weighting survival analysis of long-term survival stratified by type of combined organ transplant, accounting for donor, recipient, and operative characteristics. We identified 2,300 patients who underwent combined organ transplant (HK 1,257, HLv 212, HL 831). HL recipients were more likely white (77%), women (58%), with congenital heart disease (44.5%), and longer waiting list time (median 195 days). HK transplant increased significantly during the study period where as HL decreased significantly. Median survival was 12.2 years for HK (95% confidence intervals [CI] 10.8 to 12.8), 12 for HLv (95% CI 8.6 to 17.6) but significantly lower at 4.5 years for HL (95% CI 3.6 to 5.8). Combined HK and HLv transplantation rates are increasing and long-term survival is comparable to primary HT, unlike HL which is associated with decreasing trends and significantly lower survival.

Prevalence of BK Virus Infection in a Large Heart Transplant Population

In heart transplant (HT) patients, prevalence of BK virus (BKV) infection and its clinical significance are unknown. We sought to understand rates of BKV infection in a large HT cohort and to evaluate risk factors and effects of infection. Consecutive HT patients at a single institution were evaluated for BKV infection in blood and urine in the 1st year post-transplant. Titers were collected 1-month post-transplant and then every 6 months, with additional testing if needed. Rates of infection were compared between HT and combined organ transplant. In the HT group, patients with no infection, viruria with no viremia, and viremia with or without viruria were compared. Measures of immunity and kidney function were collected with titers in blood to evaluate Spearman rank correlations using log10 transformation. 104 patients were enrolled: 89 HT, 12 heart/kidney transplant (HKT), 1 heart/liver transplant, 2 heart/liver/kidney transplant. Viruria and viremia were highly prevalent in HT (42% and 30%, respectively). Compared to HT patients without infection, those with viremia were older (57.8 vs 50.8 yrs, p=0.04), and tended to have lower pre-transplant glomerular filtration rate (GFR) (63.3 vs 71.4 mg/dL/1.73m2, p=0.14). There were no significant differences between patients with viruria compared to viremia. 1-year freedom from viruria was 55% in HT vs 46% in HKT. 1-year freedom from viremia was 67% in HT vs 56% in HKT (Figure). Viremia titers in HT strongly correlated with immunoglobulin (IgG) levels (R= -0.60, p=0.001), but not other immunity measures. Viremia titers were not correlated with GFR (R= 0.05, p=0.70). When comparing GFR before transplant to 1-year post-transplant, there was no significant difference found in the groups with no infection, viruria, and viremia (-22.4 vs -23.7 vs -23.4 mg/dL/1.73m2, p=0.98). BK viremia is very common in HT patients. BK viremia correlated with IgG, but not kidney function. Longer surveillance studies are needed to evaluate effects of BKV infection.

PRA is Not Associated with Rejection in Combined Heart and Liver Transplantation

Combined heart liver transplantation (CHLT) is relatively rare with approximately 250 cases from 1988-2018 nationally, but with rising numbers each year due to excellent survival. CHLT outcomes have potential immunological benefits compared to heart transplant alone. Liver allografts have long been observed to be more tolerant to HLA mismatch while showing some degree of immune protection in combined organ transplantation. A retrospective analysis from our center's experience of CHLT was performed. Outcomes of patients who had pre-transplant elevated panel reactive antibodies (PRA) >50-99% were compared to those with 0% and those with a low to moderate PRA (1-50%). The hypothesis was tested with the Fisher's exact test. Between 1997 and 2019, 37 patients underwent CHLT. The average age was 42.4 years +/- 10 with 8 deaths (21.6%) ranging from day 2 to 4.5 years post-transplant (5, 13.5% within the first year). None of the deaths were due to rejection or primary graft dysfunction. There were no episodes of humoral rejection and there were 2 episodes (5.4%) of cellular rejection in hearts and 4 (10.8%) in livers (of these, one episode was dual organ rejection). There was no statistical significance at baseline between PRA and history of Fontan physiology, protein losing enteropathy, prior sternotomy, diabetes, hypertension or renal disease. Furthermore, there was no correlation between PRA and death, rejection of either organ, presence of donor specific antibodies, ejection fraction below 50% (1 month and 1 year), length of stay over 30 days, post-transplant hypertension, diabetes or renal disease (table 1). The degree of allosensitization was not associated with worse outcomes in the CHLT population. While the sample is small, it is a reassuring finding that may change the perception of risk when planning a CHLT in a highly sensitized patient.

Temporal Trends and Outcomes of Patients Undergoing Combined Organ Transplantation: Insights from the United Network for Organ Sharing (UNOS)

Studies have shown that highly selected patients undergoing combined heart-kidney (HK) and heart-liver transplants (HL) have short- and long-term outcomes comparable to those observed in primary heart transplantation (HT). Adults patients with stage D heart failure that underwent combined HK, HLv and heart-lung (HL) were identified in the United Network for Organ Sharing (UNOS) registry between 1991 and 2016, with follow-up through March 2018. We conducted inverse-probability weighted estimator (IPWE) survival analysis of long-term survival stratified by type of combined organ transplant, accounting for donor, recipient and operative characteristics. We identified 2300 patients who underwent combined organ transplant (HK: 1,257, HLv: 212, HL: 831). HL recipients were more likely white (77%), females (58%), with congenital heart disease (44.5%), and longer waiting list time (median 195 days). HK transplant increased significantly during the study period where as HL decreased significantly (Figure). Median survival was 12.2 years for HK (95% Confidence intervals [CI], 10.8-12.8), 12 for HLv (95% CI 8.6-17.6) but significantly lower at 4.5 years for HL (95% CI 3.6-5.8) (Figure). Combined HK and HLv transplantation rates are increasing and long-term survival is comparable to primary HT, unlike HL which is associated with decreasing trends and significantly lower survival.

Severe Primary Graft Dysfunction: Impact of the New UNOS Heart Allocation System

Primary graft dysfunction (PGD) is a leading cause of early morbidity and mortality following heart transplantation (HTx). The purpose of this study was to determine the mortality risk and incidence of PGD pre- and post-implementation of the new UNOS heart allocation policy. A total of 426 consecutive adult patients underwent HTx from 1/2010 to 5/2019. Recipients of combined organ transplants were excluded. Definition of severe PGD was based on the 2014 ISHLT consensus statement which includes dependence on mechanical circulatory support, excluding requirement for intra-aortic balloon pump (IABP). The primary outcome was the incidence of PGD and overall 1-year survival. The cohort studied was predominantly male (70.8%), with a mean age of 53.4±12.8 years; 31.6% were supported with a left ventricular assist device as a bridge to HTx, and 38.4% were blood type O. There were 17 (4.0%) cases of severe PGD, all of which required extracorporeal membrane oxygenation support. Baseline characteristics pre-HTx were similar in those with and without PGD (Figure 1). There was no difference in the incidence of severe PGD following the introduction of the new allocation policy in October 18, 2018 (5.9 vs. 4.5%, p=0.70), but there was a significant increase in the use of post-transplant IABP (23.5 vs. 9.1%, p=0.009). There was no correlation between RADIAL score and incidence of severe PGD (p=0.41). Severe PGD was associated with reduced 30-day survival (97.6% [95% CI: 95.5-98.8] vs. 68.7% [40.5-85.6], p<0.001) and 1-year survival (92.4% [95% CI: 89.1-94.7] vs. 50.0% [95% CI: 24.5-71.1], p<0.001). (Figure 1). Patients with severe PGD had an 8.6-fold increased risk of death when adjusted for age (p<0.001). Incidence of severe PGD has not increased in the contemporary era with the new UNOS heart allocation policy. PGD is associated with poor 1-year survival and is not predicted by the RADIAL score, which underscores the need for a new risk prediction model.