Post-transplant Variables Research Articles

Machine Learning Model to Predict Graft Rejection After Kidney Transplantation

There are few predictive studies about early posttransplant outcomes taking into account baseline and posttransplant variables. The objective of this study was to create a predictive model for 30-day graft rejection using machine learning techniques. Retrospective study with 1255 patients undergoing transplant from living and deceased donors at a tertiary health service in Brazil. Recipient, donor, transplantation, and postoperative period data were collected from physical and electronic records. We split the data into derivation (training) and validation (test) datasets. Five supervised machine learning algorithms were developed with this subset of variables in the training set: Simple Logistic Regression, Lasso, Multilayer Perceptron, XGBoost, and Light GBM. There were 147 (12.48%) cases of graft rejection within 30 days of transplantation. The best model was XGBoost (accuracy, 0.839; receiver operating characteristic area under the curve, 0.715; precision, 0.900). The model showed that deceased donor transplantation, glomerulopathy as an underlying disease, and donor's use of vasoactive drugs had more than 20% importance as rejection risk factors. The variables with the greatest predictive values were thymoglobulin induction and delayed graft function. We fitted a machine learning model to predict 30-day graft rejection after kidney transplantation that reaches a higher accuracy and precision. Machine learning models could contribute to predicting kidney survival using nontraditional approaches.

Validation and performance of three scoring systems for predicting primary non-function and early allograft failure after liver transplantation

BackgroundPrimary non-function (PNF) and early allograft failure (EAF) after liver transplantation (LT) seriously affect patient outcomes. In clinical practice, effective prognostic tools for early identifying recipients at high risk of PNF and EAF were urgently needed. Recently, the Model for Early Allograft Function (MEAF), PNF score by King's College (King-PNF) and Balance-and-Risk-Lactate (BAR-Lac) score were developed to assess the risks of PNF and EAF. This study aimed to externally validate and compare the prognostic performance of these three scores for predicting PNF and EAF. MethodsA retrospective study included 720 patients with primary LT between January 2015 and December 2020. MEAF, King-PNF and BAR-Lac scores were compared using receiver operating characteristic (ROC) and the net reclassification improvement (NRI) and integrated discrimination improvement (IDI) analyses. ResultsOf all 720 patients, 28 (3.9%) developed PNF and 67 (9.3%) developed EAF in 3 months. The overall early allograft dysfunction (EAD) rate was 39.0%. The 3-month patient mortality was 8.6% while 1-year graft-failure-free survival was 89.2%. The median MEAF, King-PNF and BAR-Lac scores were 5.0 (3.5–6.3), -2.1 (-2.6 to -1.2), and 5.0 (2.0–11.0), respectively. For predicting PNF, MEAF and King-PNF scores had excellent area under curves (AUCs) of 0.872 and 0.891, superior to BAR-Lac (AUC = 0.830). The NRI and IDI analyses confirmed that King-PNF score had the best performance in predicting PNF while MEAF served as a better predictor of EAD. The EAF risk curve and 1-year graft-failure-free survival curve showed that King-PNF was superior to MEAF and BAR-Lac scores for stratifying the risk of EAF. ConclusionsMEAF, King-PNF and BAR-Lac were validated as practical and effective risk assessment tools of PNF. King-PNF score outperformed MEAF and BAR-Lac in predicting PNF and EAF within 6 months. BAR-Lac score had a huge advantage in the prediction for PNF without post-transplant variables. Proper use of these scores will help early identify PNF, standardize grading of EAF and reasonably select clinical endpoints in relative studies.

Analysis of US Registry Data on Patient Characteristics, Treatment Patterns and Outcomes of Patients Receiving Extracorporeal Photopheresis with or without Ruxolitinib

Background Chronic Graft vs. Host Disease (cGvHD) occurs in up to 60% of long-term survivors of allogeneic hematopoietic cell transplantation (alloHCT) and is associated with substantial morbidity and mortality. 1 Extracorporeal photopheresis (ECP) is an immunomodulatory therapy that has been used in the treatment of cGvHD, often in combination with steroids or other established immunosuppressants. The purpose of this retrospective analysis of a registry database is to understand how ECP is being used within the real-world setting especially with introduction of newer immunosuppressants in particular ruxolitinib (RUX). Methodology Data from the Center for International Blood and Marrow Transplant Research (CIBMTR) Registry was used. Inclusion criteria were patients in the United States who received an alloHCT during 2017 to 2019, were diagnosed with cGvHD within twelve months following alloHCT and received ECP for the treatment of cGvHD. Only data from centres who completed the Comprehensive Report Forms were included. For the analysis pre-specified end points were: Overall survival (OS) from date of first ECP±RUX treatment, and 'GvHD presence’ and 'GvHD still being treated with steroids or Immunosuppressants’ at last contact. Data was analysed by recipient, disease, transplant and post-transplant variables. OS survival was estimated by the Kaplan-Meier method. Results Of 2,435 patients who developed cGvHD within one year of alloHCT, 200 patients (8.2%) from 69 centres were eligible for the analysis. Median follow-up among all survivors was 35 months. The median age was 56 years (including 20 paediatric patients with median age of 11 years), 57% were males, and 70% White (Table). The majority of patients had prior aGvHD (79%), extensive cGVHD (95%) and were transplanted for a malignant disease (91%). Approximately 48% (n=96) of study patients had ECP in combination with ruxolitinib (ECP +RUX), either simultaneously, overlapping or sequential, with slightly younger age (55 vs 57 years) and higher percent of Caucasians (77% vs 63%) than ECP patients (n=104) without RUX (ECP-RUX)). The median time from cGVHD onset to ECP± RUX was 3 overall (range 0-43), 2 months for the ECP+RUX group and 3 months for ECP-RUX. For the ECP+RUX group, 52 (54%) patients had ECP treatment first and 38 (40%) had RUX treatment first (4 were same day and 2 unreported). Median time to switch or add in either ECP or RUX was 3 months and for 35% (33/96) of patients this occurred <1 month. The overall survival at year 1 and 2 following ECP+RUX or ECP-RUX treatment, were 77.4% vs 69.6% and 64.7% vs 52.9% (p=0.110), . Overall cGvHD presence at last contact was still high at 88% (n=176/200) and 53% (105) of patients were still taking steroids, while 63 patients (37%) stopped after ECP± RUX were initiated (10 patients stopped prior to initiation and for 12, the stop date was not reported) . In the ECP -RUX group 57% (19 /33) of patients stopped steroids < 6 months, compared to 30% (9/30) in ECP+RUX. Overall, 70% (139) were still taking an immunosuppressant agent (other than steroids), 74% and 65% in RUX+ECP and RUX-ECP, respectively. Conclusion Results from this CIBMTR study using recent data show that ECP is used to primarily treat patients with extensive cGvHD. In nearly half the patients RUX was used in combination with ECP. Some differences were observed in characteristics and outcomes in the ECP group with and without RUX. Not all clinical outcomes and measures (in particular cGVHD response rates) were reported by centers or were only available at baseline, and data on all agents used to treat GvHD was not analysed. Despite these limitations, while cGvHD still persists in most patients, over a third of patients in our analyses were able to stop steroids . References 1 Lee SJ, Vogelsang G, Flowers ME. Chronic graft-versus-host disease. Biol. Blood Marrow Transplant. 2003;9(4):215-233 Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

417.3: Results of 922 Pediatric Liver Transplants: Prognostic Factors, Learning Curve and Impact on One-Year Survival

Objective: The objective of this work is to analyze the impact on one-year survival of pediatric liver transplanted patients during 29 years of the transplantation program at the “Prof. Dr. J.P. Garrahan ”. Materials and Methods: 922 pediatric liver transplants were retrospectively studied, including prognostic factors and the experience curve, and comparing two different stages: Era I (1992-2005) and Era II (2005-2021). Pre, intra and post-transplant variables were defined. A univariate and multivariate logistic regression analysis was performed to evaluate the predictors of mortality and graft loss at one year. Results: The median weight of patients was 13 kg and the most frequent indication for transplantation was biliary atresia (35%). The living related donor represented 27% of the transplants and those performed with cadaveric liver were: with whole liver (34%), reduced (24%) and split (16%). The overall survival of the patient and the graft at one year was 79.75% and 75.54%, respectively. The risk factors for patient death and graft loss one year after transplantation in the multivariate analysis were: child under 10 kg at the time of transplantation, late retransplantation, liver reduction technique, use of an arterial graft, primary non function and arterial thrombosis. In Era I, there was a greater number of transplants in emergency status, a longer cold ischemia time, a lower number of late retransplants, and a lower delayed closure of the abdominal wall. Overall graft and patient survival at one year improved significantly in Era II from 66.94% to 81.56% (log rank 0.0000) and from 70.88% to 86.30% (log Rank 0.0000), respectively. Conclusion: The present work demonstrates the evolution in the learning curve over a 29 year period and its relationship with the improvement on early post-transplant survival in a transplant program that takes place in a public hospital in Argentina. The improvements achieved during the second ERA of the program are comparable to international standards and reflect the continuous improvement and experience of an interdisciplinary team.

New insights into ischemia-reperfusion injury signaling pathways in organ transplantation.

Ischemia-reperfusion injury (IRI) leading to allograft rejection in solid organ transplant recipients is a devastating event that compromises graft and patient survival. As our clinical knowledge regarding its definition and presentation has significantly improved over the last years, adequate biomarkers translating to important therapeutic intervention remains a challenge. This review will summarize recent findings in this area. In the past 18 months, our understanding of organ transplantation IRI has improved. IRI involves a positive amplification feedback loop encompassing damaged cells at the graft site, the activity of redox-sensitive damage-associated molecular patterns, and local sequestration of recipient-derived monocytes, lymphocytes and polymorphonuclear leukocytes, like neutrophils, to sustain the immunological cascade and to enhance the destruction of the foreign tissue. Recent studies have identified critical components leading to IRI, including the oxidation state of high mobility group box 1, a classic danger signal, its role in the Toll-like receptor 4-interleukin (IL)-23-IL-17A signaling axis, and the role of neutrophils and CD321, a marker for transmigration of circulating leukocytes into the inflamed tissue. In addition, recent findings imply that the protective functions mediated by autophagy activation counterbalance the detrimental nucleotide-binding domain-like receptor family, pyrin domain containing 3 inflammasome pathway. Finally, clinical studies reveal the posttransplant variables associated with early allograft dysfunction and IRI. The future challenge will be understanding how crosstalk at the molecular and cellular levels integrate prospectively to predict which peri-transplant signals are essential for long-term clinical outcomes.

Short Term Outcomes of Patients Who Underwent Lung Transplant for COVID-19 ARDS

PurposeLung transplantation is a life saving treatment option for patients with COVID-19 ARDS. We aim to assess the short-term outcomes of patients who underwent lung transplantation for COVID ARDS.MethodsThis is a single-center retrospective cohort study of patients who underwent lung transplantation for COVID 19 ARDS between 7/1/2020 and 06/30/2021. Study was IRB-approved. Baseline demographic data, pre transplant variables, peri operative data and post transplant variables were extracted. Post-transplant graft function variables were followed until 09/30/2021.ResultsTwenty patients underwent lung transplantation alone, and one patient underwent lung kidney transplantation. Nineteen patients (90%) were ECMO bridge to transplant and twenty patients (95%) were on mechanical ventilator until the transplant. These patients were followed for a median of 234 days [IQR (188-339)]. Three patients (14%) completed a one-year follow-up. Eighteen patients (86%) completed six months follow-up. None of the patients required dialysis. At the end of the follow up period, all patients have good graft function and none of the patients are on supplemental oxygen.ConclusionWith careful selection, lung transplants can be performed with reasonable post-transplant outcomes in COVID 19 ARDS patients. However, these patients tend to have a prolonged post transplant hospital stay, a median of 48 days with IQR (28.5 - 73.5). 50% of patients had at least one return to operating room post transplant for hemothorax.

Vitamin D Insufficiency Prior to Paediatric Liver Transplantation Is Associated with Early T-Cell Mediated Rejection.

Objectives: T-cell mediated rejection (TCMR) can compromise long-term liver allograft survival. The immunomodulatory properties of vitamin D are increasingly recognized. We investigated whether perturbations in vitamin D metabolism prior to LT may predispose to TCMR in a representative cohort of paediatric LT recipients. Methods: In this retrospective single-center study of children who underwent liver transplantation between 2005 and 2017, we collected serum 25(OH) vitamin D levels and other parameters related to vitamin D metabolism. Post-transplant variables were collected from medical records during the first year following LT. Results: Eighty-two patients were included. Twenty-six (32%) developed TCMR, 52 (65%) presented at least one event of 25(OH) D insufficiency during the year before the transplant, while 23 (32%) had at least one documented elevated plasma parathyroid hormone level. Forty-six patients benefited from nutritional support (56%). The development of TCMR was associated with vitamin D insufficiency pre-LT (p = 0.01). No significant correlations were identified between PTH levels and incidence of TCMR. The association was stronger in patients transplanted for cholestatic diseases (p = 0.004). Conclusions: Vitamin D insufficiency before a liver transplant may be associated with TCMR during the first year post-LT. These findings warrant further investigation.

Perioperative Desensitization for Sensitized Lung Transplant Candidates

Purpose Sensitized lung transplant (LTx) candidates have longer waiting times, decreased likelihood of transplant, and increased risk of death while on waitlist. To mitigate this and to increase the access to donor pool, for sensitized candidates, we modified and implemented The Toronto perioperative strategy to treat DSA-positive recipients with positive virtual crossmatch (VCM) donor offers. We hypothesize that such perioperative desensitization strategy can be safely implemented with acceptable outcomes and help decrease the waitlist mortality. Methods We performed a retrospective chart review of sensitized candidates who underwent LTx between June 2017 - June 2020 and required perioperative desensitization. We collected the baseline demographics and post-transplant variables. The protocol was implemented if the calculated panel reactive antibody (cPRA) was > 30 % and had positive VCM. Desensitization protocol included preoperative plasma exchange (PLEX) with 1.5 volume, intra operative basiliximab induction, followed by five sessions of PLEX, intravenous immunoglobulin (IvIg, 1 gm / kg) and Anti Thymocyte globulin (dose 3 mg/kg for VCM positive vs 5 mg/kg for positive actual crossmatch (ACM)). We used tacrolimus (12 - 15 ng/ml), mycophenolate and prednisone for maintenance immunosuppression. Results 25 patients required desensitization. 76% (n=19) of them are females. Median LAS score is 41.3 (IQR 33.87-60.33). Median wait time was 28.9 days (IQR 12.6-65). All patients underwent bilateral lung transplantation. ACM was positive in 24% of patients (n=6). 76% (n=19) completed the protocol. Incidence of Primary graft dysfunction at any time point was 12% (n=3). Acute cellular rejection >= grade 2 was 8% (n=2). 8% (n=2) had chronic lung allograft dysfunction. Overall survival of this cohort is 96% with a median follow up of 17 months (IQR 5 - 25.5). Conclusion Perioperative desensitization can be safely implemented with acceptable outcomes in sensitized LTx candidates. On comparison of our SRTR data, before and after desensitization implementation, we noted a decline in the waitlist mortality (11.4% to 7.6%) and 50th percentile median wait times (8.5 months to 1.3 months).

Characteristics and outcomes among patients with community‐acquired respiratory virus infections during the first year after lung transplantation

The current study describes the spectrum of community-acquired respiratory infections (CARV) during the first year after lung transplantation (LT). Additionally, we elucidate variables associated with CARV, management strategies utilized, and impact on early and late outcomes. This was a retrospective study among patients transplanted between 2012 and 2015 (n=255, mean age 55.6±13.5years, M: F 152:103). The diagnosis of CARV was based on the multiplex PCR on nasopharyngeal swab samples. Baseline characteristics, post-transplant variables, and outcomes were compared among patients with and without CARV. Eighty CARV infections developed among a quarter of the study group (n=62, 24.3%). Rhinovirus/enterovirus was the most commonly isolated CARV (n=24) followed by coronavirus (n=17) and RSV (n=9). A significant proportion of episodes (43.8%) required hospitalization. The use of nasal corticosteroids and left single LT was independently associated with an increased risk of CARV. CARV infections did not impact the lung functions during the first year or the CLAD-free survival at 3years. There is a significant burden of CARV infections during the first year after LT. The use of nasal corticosteroids may increase the risk of CARV infection. CARV infections did not impact outcomes.

The effect of human leukocyte antigen A1 and B35-Cw4 on sustained BK polyomavirus DNAemia after renal transplantation.

Human leukocyte antigen (HLA) class I presentation pathway plays a central role in natural killer (NK) cell and cytotoxic T-cell activities against BK polyomavirus (BKPyV) DNAemia. We determined the risk of sustained BKPyV DNAemia in 175 consecutive renal transplant recipients considering the simultaneous effect of donor/recipient HLA class I antigens and pre- or post-transplant variables. Median (IQR) age was 53 (44-64) years, and 37% of patients were female. 40 patients (22.9%) developed sustained BKPyV DNAemia [median (IQR) viral load: 9740 (4350-17125) copies/ml]. In the Cox proportional hazard analysis, HLA-A1 (HR: 3.06, 95% CI: 1.51-6.17) and HLA-B35-Cw4 (HR: 4.63, 95% CI: 2.12-10.14) significantly increased the risk of sustained BKPyV DNAemia, while 2 HLA-C mismatches provided a marginally protective effect (HR: 0.32, 95% CI: 0.10-0.98). HLA-Cw4 is a ligand for NK cell inhibitory receptor, and HLA-B35 is in strong linkage disequilibrium with the HLA-Cw4 allele. The association between HLA-B35-Cw4 expression and sustained BKPyV DNAemia supports the important role of cytotoxic T cells and NK cells that would normally control BKPyV activation through engagement with immunoglobulin-like killerreceptors(KIRs). Further studies are required to investigate the effect of HLA-C alleles along with NK cell activity against BKPyV DNAemia.

Seeing the Forest for the Trees: Random Forest Models for Predicting Survival in Kidney Transplant Recipients.

Seeing the Forest for the Trees: Random Forest Models for Predicting Survival in Kidney Transplant Recipients.

Effectiveness of a Home-Based Pre-Habilitation Program for Lung Transplant Candidates - A Retrospective Chart Review

Home-based exercise programs offer an alternative way to provide exercise pre-transplant; it gives access to rehabilitation to a larger number of patients and it may be associated with lower healthcare cost. We described the changes in functional exercise capacity (6-minute walk distance (6MWD)) in lung transplant candidates who participated in a home-based exercise program and evaluated relationships between changes in functional exercise capacity pre-transplant and post-transplant variables. Retrospective cohort study of 159 individuals who received a lung transplant between 2011-2015, who participated in a home-based exercise program while waiting for transplantation and had available pre-transplant data. Our primary outcome was 6MWD at 3 time points: time of assessment for transplant, last test prior to transplant and one-month post-transplant. Other variables included: age, sex, primary diagnosis, date of transplantation, body mass index (BMI), total hospital length of stay (LOS), intensive care unit (ICU) LOS and time on mechanical ventilation. The median LOS on the waiting list was 1.9 yrs. There was a mean decrease of 28±93.9m between the 6MWD at the time of assessment and the last 6MWD prior to transplantation (p<0.001; whole sample). Forty-one patients (25.8%) increased their 6MWD (mean change +85.8±42.8m); 72 patients (45.3%) decreased their 6MWD (mean -109.8±71.2m); and 46 patients (28.9%) had no change in 6MWD (-1.5±15.7m). There was a weak negative correlation between change in 6MWD prior to transplant and time on mechanical ventilation (r= -0.185; p=0.034). On multiple linear regression, change in 6MWD prior to transplant was not associated with the time on mechanical ventilation, total hospital LOS nor ICU LOS when adjusted for age, gender, BMI. The majority of the patients (54.7%) were able to either increase or maintain their 6MWD by participating in a home-based pre-habilitation program while on the waiting list. These results are similar to what has been found for hospital-based programs in lung transplant candidates. *Financial support: Funded by the Canadian Society of Transplantation-Allied Health Group Research Grant (2017). Dr Massierer holds the Quebec Respiratory Health Network (RHN) Scholarship Supplement Program Award. Dr Janaudis-Ferreira holds FRQS Junior 1 career award.

Impact of Donor Hemodynamics on Heart Transplant Outcomes: Using Machine Learning Techniques

Several studies have evaluated the role of recipient hemodynamics on heart transplant (HTx) outcomes. Data on the role of donor hemodynamics and donor-related characteristics on outcomes is scarce. We studied adult (≥18 years) Htx patients from 1997 and 2016 using the UNOS database that had donor right heart catheterization information. Primary study endpoint was the composite of 1-year mortality or re-transplant. We utilized Machine Learning (ML) method and Logistic Regression (LR) to explore predictive variables associated with the primary outcome. We excluded post-transplant variables, donors with missing demographic data and improbable hemodynamics. Receiver operating characteristic (ROC) curve was constructed to investigate the discrimination ability of the model. We included 4,053 Htx recipients where donors had received right heart catheterization. Median recipient age was 55 years and 76.7% were male. Prominent donor characteristics included a median donor age of 36 years (IQR 25-45 years), 69.3% male sex, 69.5% Caucasian by race, 22.8% with smoking history, 15.1% with heavy alcohol use, and 17.3% had known cocaine use. The ML models reasonably predicted one-year mortality or retransplantation (XGBoost AUC 0.64, AutoML AUC 0.66). The LR model showed a poorer predictability of the primary study endpoint (AUC 0.60). Recipient characteristics such as total bilirubin, serum creatinine, ventilator use, and donor characteristics such as donor age and right ventricular mass were predictive of outcomes in both models. No additional donor characteristics including hemodynamics predicted the primary endpoint. Donor age and donor right ventricular mass were predictive of outcomes in both ML and LR models. Other donor characteristics including hemodynamics did not improve model predictability. Recipient characteristics significantly outweigh those of donor in predicting one-year mortality or retransplantation following Htx.

Risk Factors for Post-Transplant Outcomes in Patients with LVAD Support: A Machine Learning and Logistic Regression of the UNOS Database

Shortage of organs for transplantation and improvements in LVADs make the use of this technology common as bridge to transplant (BTT). Compared to traditional statistical methods, machine learning (ML) techniques provides improvement in predictive modeling, identifying dimensionality and non-linear relationships between variables. Thus, we investigated specific risk factors that predispose to poor outcomes in pts supported with LVAD as BTT using ML and logistic regression (LR). We included all pts that had heart transplant between 2006 and 2016. The primary outcome was the composite of 1-year mortality and re-transplant. We utilized ML method and LR to find the most predictive variables associated with the primary outcome. We excluded post-transplant variables. Receiver operating characteristic (ROC) curve was constructed to investigate the discriminatory capacity of the model. Of 18,612 pts (52±12 years, 24.58% female), 7,700 (41.12%) were on LVAD support. The discriminatory capacity predicting the primary outcome using the same variables modeled with ML or LR methods was similar in pts with LVAD or without the device (AUCs 0.61 and 0.63, respectively) (Figure A and B). Using ML and LR, the top 5 variables that were associated with poor outcomes in pts supported with LVAD were the recipient total bilirubin, creatinine, predicted right ventricular (RV) mass, and total albumin, as well as ischemic time during transplant. For pts without LVAD, the top 5 variables that were identified using ML and LR, were recipient total bilirubin, creatinine, and ventilator use, as well as ischemic time and distance of the donor. Both ML and LR methods identified total bilirubin, creatinine, and ischemic time among the strongest risk predictors of poor outcomes after transplant in pts with and without an LVAD. Notably predicted RV mass of the recipient was an important variable for pts with LVAD as a BTT.

Psoas Muscle Index Does Not Predict Post-Transplant Outcomes: A Series of 57 Liver Transplant Recipients

BackgroundSarcopenia is defined as the loss of muscle mass and function. Our aim is to evaluate the degree of sarcopenia by measuring the patients on the waiting list for liver transplantation and its influence on the different post-liver transplant outcomes in our group. MethodsThe psoas muscle index (PMI, cm2/m2) was calculated (right psoas muscle area [cm2]/the square of the body height [m2]) in 57 patients on the waiting list for liver transplantation in our center, and the post-transplant variables relevant to our study were collected. ResultsThe 57 recipients had a mean age of 57 years (range, 35-73) and had a mean of 7.4 months (range, 0-39) on the liver transplant waiting list. The mean psoas muscle index was 2.39 (range, 1-4), and the mean body mass index was 28.01kg/m2 (range, 22-36). After multivariate analysis we found a positive correlation between the PMI and the body mass index of the recipients (r = 0.320, P = .017), intensive care unit length of stay, and donor age (r = 0.319, P = .042), and between cold ischemia time and graft survival (r = 0.366, P = .009). We found no correlation in our sample between PMI and post–liver transplant complications either in terms of graft or patient survival. ConclusionPMI is not representative of total muscle mass and sarcopenia and is not effective in adequately predicting the survival of patients on the waiting list for liver transplantation.

P3A.03: Pre-, peri-, and post-operative predictors of survival after intestinal transplantation: results from a single-center analysis.

Introduction: Intestinal transplantation (ITx) can be a successful procedure for select candidates with intestinal failure (IF). However, there is limited data on variables and characteristics that predict successful outcome. The aim of this study was to analyze a large dataset to determine outcome predictors. Methods: An IRB approved, prospective database has been maintained since the inception of the program in 1991. Patient inclusion was closed in December 2018. All recipients of intestinal grafts were included. Multiple pre-, peri, and post-transplant variables (n = 35) were collected and included in the analysis. The end point was 1-year patient and graft survival. Standard statistical analysis was undertaken. Results: 128 patients underwent 151 ITx including 35 isolated intestine (I-ITx), 77 liver-intestine (OLT-SBT), 29 multivisceral (MVT) and 11 modified multivisceral (MMVT). 58% were male, 78% were children, and 77% had surgical IF etiologies. At ITx, the median MELD/PELD at ITx was 34 with 43% hospitalized. The majority of patients received induction immunotherapy with either interleukin-2 receptor antagonist [IL2RA] (58%) or antibody induction with rabbit antithymocyte globulin [rATG] / OKT3 (34%). Relevant patient clinical characteristics are summarized in the table below: Significant predictors for improved graft survival were: Recipient weight (<20 kg), age group (pediatrics), graft type (liver inclusive intestinal graft), panel reactive antibody < 20%, absence of donor specific antibodies, negative crossmatch, warm ischemia time < 1 hr, use of induction immunosuppression, ventilator time < 7 days, length of stay < 80 days, and transplant era (2001–2018). Significant predictors for improved patient survival were: Cold ischemia time < 10 hrs, warm ischemia time < 1 hr, absence of recipient splenectomy, use of induction immunosuppression, length of stay < 80 days, and transplant era (2001–2018). The patient and graft survival at 1-year was 82% and 69%. Conclusion: The results of ITx have improved over time. Several perioperative factors were identified that impact early outcome. Especially important for graft survival are variables that can be altered including donor: recipient match, preformed donor specific antibodies, ischemia times, and immunosuppression. Further investigations are required to improve ITx outcomes.

KINDERGARTEN-AGE QUALITY OF LIFE OUTCOMES AFTER LIVER TRANSPLANTATION AT &lt;6 YEARS

Abstract BACKGROUND Given the improved mortality after paediatric liver transplantation, health related quality of life (HRQL) is an important outcome measure and provides valuable information for families. OBJECTIVES To determine the HRQL of kindergarten-age children who have undergone liver transplantation at age &lt;6 years old. DESIGN/METHODS Between 1999–2014, all paediatric liver transplant recipients at our center were enrolled in this ethics board approved, longitudinal inception-cohort study. Following informed consent, HRQL was measured using the parent completed Pediatric Quality of Life Inventory, version 4.0 (PedsQL). The association between pre-transplant, transplant, and post-transplant variables and HRQL was examined using multiple regression analyses. Scores were compared to normative scores for HRQL in 8700 children [total PedsQL 82.2 (15.5), psychosocial summary 81.2 (15.3), and physical summary 84.0 (19.7)] and to scores for 130 children with surgical congenital heart disease from early infancy [81.1 (13.9), 77.5 (16.4), and 86.4 (15.3) respectively]. RESULTS 78 liver transplants for children &lt;6 years of age were performed; 69 patients (88.5%) survived, and all (100%) were assessed at 55.4 (7.2) months of age: 38 with biliary atresia, 11 with acute liver failure, 11 with cholestasis, and 9 with metabolic disease. The mean total PedsQL was 75.6 (SD=15.6), psychosocial summary 72 (15.9) [a composite of emotional functioning 73.8 (16.4), social functioning 74.6 (19.2), and school functioning 70.6 (19.1)], and physical summary 78.2 (20.9). These composite scores were all statistically significantly different from population norms (p&lt;0.001, &lt;0.001, 0.026 respectively) and surgical congenital heart disease patients (p=0.015, 0.029, 0.005). The proportion having a score &gt;1 (expected 15.9%) and &gt;2 (expected 2.27%) SD below population norms were: total PedsQL 20.6% and 11.8%, psychosocial summary 32.3% and 11.3%, and physical summary 19.1% and 7.4%. Having a wait-list status 1 on the Canadian System of Classification was associated with higher total PedsQL (Effect size 9, 95%CI 2, 16; p=0.018) and physical summary (Effect size 15, 95%CI 16, 79; p=.004). None of the perioperative variables were predictive for psychosocial summary. Variables not associated with PedsQL included metabolic disease, PELD score, growth failure, any post-operative severe complication, age at transplant, weight at transplant, socioeconomic status, and year of transplant. CONCLUSION HRQL after liver transplantation is lower than population norms and congenital heart disease patients. More research is needed to determine why HRQL is low in order to improve the lives of these children.

Resource Utilization for Initial Hospitalization in Pediatric Heart Transplantation in the United States

Pediatric heart transplantation (HT) is resource intensive. Event-driven pediatric databases do not capture data on resource use. The objective of this study was to evaluate resource utilization and identify associated factors during initial hospitalization for pediatric HT. This multicenter retrospective cohort study utilized the Pediatric Health Information Systems database (43 children's hospitals in the United States) of children ≤19 years of age who underwent transplant between January 2007 and July 2013. Demographic variables including site, payer, distance and time to center, clinical pre- and post-transplant variables, mortality, cost, and charge were the data collected. Total length of stay (LOS) and charge for the initial hospitalization were used as surrogates for resource use. Charges were inflation adjusted to 2013 dollars. Of 1,629 subjects, 54% were male, and the median age at HT was 5 years (IQR [interquartile range] 0 to 13). The median total and intensive care unit LOS were 51 (IQR 23 to 98) and 23 (IQR 9 to 58) days, respectively. Total charge and cost for hospitalization were $852,713 ($464,900 to $1,609,300) and $383,600 ($214,900 to $681,000) respectively. Younger age, lower volume center, southern region, and co-morbidities before transplant were associated with higher resource use. In later years, charges increased despite shorter LOS. In conclusion, this large multicenter study provides novel insight into factors associated with resource use in pediatric patients having HT. Peritransplant morbidities are associated with increased cost and LOS. Reducing costs in line with LOS will improve health-care value. Regional and center volume differences need further investigation for optimizing value-based care and efficient use of scarce resources.

Prognostic factors to predict outcome of reduced intensity allogeneic haematopoietic cell transplantation for chronic lymphocytic leukemia.

Despite advances in immunochemotherapy CLL remains an incurable disease.. Allogeneic haematopoietic cell transplantation (HCT) has proven curative potential with ability to overcome adverse prognostic factors, however due to its toxicity it is generally perceived as the last option. We performed retrospective study to explore the outcomes and possible determinants of survival in the unselected consecutive cohort of 68 CLL patients (median age 59 years) receiving reduced intensity HCT as a part of salvage therapy in 2 Czech centers. The median interval from diagnosis to HCT was 69 months with median 3 of prior regimens, all patients were refractory to purine analogues. 49% of patients were transplanted with advanced (i.e. refractory or progressive disease or CR/PR>3), 38% had high risk cytogenetics. With median follow-up of 35 months the 3-year Kaplan-Meier survival probability for OS and PFS were 39% and 26%, respectively. Altogether 18 patients (26%) have relapsed or progressed. During the follow-up 41 patients died, 32 (78%) of transplant related factors (NRM), the others of relapse or disease progression.Univariate analysis failed to identify any clinical and pre- or post-transplant variables having clear prognostic significance for OS or PFS. The marginal OS advantage favoring HCT performed recently was detected (3-year OS: 31% for HCT until 2006 and 47% thereafter, p=0.0923). In multivariable hazards model only the female donors were associated with shorter OS (HR 2.278, p=0.016) whereas transplanted T-cell> 2.75x108/kg predicted inferior PFS(HR 1.957, p=0.035). No prognostic impact of donor type, age of donor and recipient, HLA mismatch, disease status pre-HCT, number of previous therapy lines, interval from dg. to HCT and number of transplanted hematopoietic cells was found. Our findings support the conclusion that alloHCT is able to overcome well known negative cytogenetic prognostic factors and that preferring male to female donors could be beneficial.

Patients with psychotic disorders in solid-organ transplant.

Psychotic disorders are considered a relative or absolute contraindication to organ transplant, but information about their impact on transplant is limited. To describe the clinical course of psychotic patients while they were on the waiting list and the outcomes of patients with psychotic disorders undergoing evaluation for organ transplant. Thirty-eight transplant candidates with a diagnosis of psychotic disorder were analyzed in this descriptive study. The following variables were collected before transplant: demographics, type of transplant, cause of organ failure, medical comorbid conditions, and psychiatric variables (diagnosis, hospitalizations, treatment, substance abuse, family history, suicide attempts). For transplant recipients, the following posttransplant variables were recorded: rejection, toxic effects of medication, nonadherence, psychotic episodes (number, time interval after transplant), and number of hospitalizations. Of the 38 transplant candidates, 34 had a history of psychotic disorder before transplant. Nineteen (56%) of the 34 were listed for transplant, and 10 (29%) underwent transplant. Median follow-up time was 1.9 (IQR, 0.16-17.9) years. Among organ recipients with a history of psychotic disorders, psychiatric hospitalizations were 0.42 per patient per year (PPY), psychotic episodes 0.68 PPY, rejection 0.21 PPY, and toxic effects of immunosuppressants 0.05 PPY. None of the recipients lost their graft. Patients with a history of psychotic disorder can do well after organ transplant. Further studies are needed with factor analyses including severity of psychosis, medication adherence, and associated comorbid conditions.