De Novo Malignancy After Adult-to-Adult Living Donor Liver Transplantation: A Single-Center Long-Term Experience

BackgroundThe incidence of de novo malignancy (DNM) after liver transplantation (LT) is reported to be 3.1% to 14.4%. It is a known cause of death in long-term recipients. This study aimed to clarify the clinical features and risk factors of DNM.MethodsRecipients who underwent adult-to-adult living-donor LT (LDLT) and survived for >6 months were investigated. The medical records were retrospectively reviewed. This study was approved by the institutional review board.ResultsIn total, 180 patients were included. The indications for LDLT were hepatocellular disease (n = 62), metabolic liver disease (n = 50), cholestatic disease (n = 46), acute liver failure (n = 12), and others (n = 10). The median age at LDLT was 48 (18-71) years, and the follow-up period was 15 (0-29) years. De novo malignancy was diagnosed in 24 recipients (28 sites), including the digestive tract (n = 9), genitourinary (n = 5), gynecologic (n = 5), lung (n = 4), hematological (n = 3), and others (n = 2). The median duration from LDLT to DNM was 7 (0-19) years. Four patients were lost to follow-up due to advanced-stage cancer. R0 (curative treatment) for non-hematological DNM was achieved in 19 lesions (95%). The 10- and 20-year DNM incidence rates were 11% and 20%, respectively. The 20-year survival rates of DNM (59.6%) and non-DNM (59.9%) patients were not significantly different. De novo malignancy was significantly higher in patients with primary sclerosing cholangitis than in others (P < .05).ConclusionsEven in DNM recipients, early detection of malignancy and R0 treatment promises long-term outcomes comparable to those of non-DNM recipients.     

Immunophenotypic Pattern of De Novo Malignancy After Liver Transplantation

Long-term survival after liver transplantation is affected by de novo neoplasia. The incidence of this type of malignancy is increased in the setting of immunosuppressive therapy. The aim of this study was to characterize the immunologic pattern of liver transplant recipients with de novo malignancies. Fifty-one liver recipients were studied, 19 of whom had a history of de novo neoplasia. Immunophenotypic patterns among patients with/without tumors were compared. The subpopulations of CD4⁺ T lymphocytes and CD8⁺ T lymphocytes differed between the 2 types of patients studied. In patients with tumor, activation membrane markers in CD4⁺ T lymphocytes and CD8⁺ T-lymphocytes, such as CD56 or CD25, were expressed in a greater proportion, whereas activation markers CD314 and CD16 were reduced in CD56^bright natural killer (NK) cells. We concluded that cytotoxic response seems to be more activated in de novo neoplasia patients, which highlights the still unknown malignancy risk effect on these immune cells.     

Predictive Factors of De Novo Malignancies After Living-Donor Liver Transplantation: A Single-Center Experience

BackgroundDe novo malignancies are a major reason of long-term mortalities after liver transplantation. However, they usually receive minimal attention from most health care specialists. The current study aims to evaluate our experience of de novo malignancies after living-donor liver transplantation (LDLT).MethodsWe reviewed the data of patients who underwent LDLT at our center during the period between May 2004 and December 2018.ResultsDuring the study period, 640 patients underwent LDLT. After a mean follow-up period of 41.2 ± 25.8 months, 15 patients (2.3%) with de novo malignancies were diagnosed. The most common de novo malignancies were cutaneous cancers (40%), post-transplantation lymphoproliferative disorders (13.3%), colon cancers (13.3%), and breast cancers (13.3%). Acute cellular rejection (ACR) episodes occurred in 10 patients (66.7%). Mild ACR occurred in 8 patients (53.3%), and moderate ACR occurred in 2 patients (13.3%).All patients were managed with aggressive cancer treatment. The mean survival after therapy was 40.8 ± 26.4 months. The mean overall survival after LDLT was 83.9 ± 52.9 months. Twelve patients (80%) were still alive, and 3 mortalities (20%) occurred. The 1-, 5-, and 10-year overall survival rates after LDLT were 91.7%, 91.7%, and 61.1%, respectively. On multivariate regression analysis, smoking history, operation time, and development of ACR episodes were significant predictors of de novo malignancy development.ConclusionsLiver transplant recipients are at high risk for the development of de novo malignancies. Early detection and aggressive management strategies are essential to improving the recipients’ survival.     

Outcomes Following De Novo CNI-Free Immunosuppression After Heart Transplantation: A Single-Center Experience

Renal impairment at the time of heart transplantation complicates the choice of subsequent immunosuppressive therapy. Calcineurin (CNI)-free regimens utilizing proliferation signal inhibitors (PSI) may mitigate against nephrotoxicity in this group; however, their effectiveness remains unclear.
We present our 7-year experience with de novo CNI-free, PSI-based immunosuppression after heart transplantation. Of the 152 patients transplanted between July 1999 and July 2006, de novo immunosuppression regimens were 49 CNI-free, PSI-based, 88 CNI, 15 combination of CNI+PSI.
Pretransplant creatinine clearance improved within 6 months in the PSI group (0.69 ± 0.34 mL/s vs. 1.00 ± 0.54 mL/s, p < 0.05) but not the CNI (1.32 ± 0.54 mL/s vs. 1.36 ± 0.53 mL/s, p = ns) or CNI+PSI (1.20 ± 0.24 mL/s vs. 1.20 ± 0.41 mL/s, p = ns) groups. The PSI group had more episodes of early (≤6 months) acute rejection, bacterial or fungal infections and pleural effusions but less CMV infection (p < 0.05 for all comparisons). Early CNI addition occurred in 37% of the PSI group for acute rejection. 33% of the entire cohort changed immunosuppression regimens over 3.6 ± 2.2 years follow-up.
De novo CNI-free, PSI-based immunosuppression in patients with significant renal dysfunction allowed significant posttransplantation renal recovery but with increased early acute rejection, bacterial and fungal infections and pleural effusions.     

Risk Factors for Development of Biliary Stricture After Liver Transplant in Adult Patients: A Single-Center Retrospective Study

Identification of risk factors for biliary stricture after liver transplant and its potential prevention is crucial to improve the outcomes and reduce the complications. We retrospectively analyzed donor and recipient characteristics with intraoperative and postoperative parameters to identify the risk factors for development of post-transplant anastomotic and nonanastomotic biliary strictures with additional analysis of the time onset of those strictures. A total of 412 patients were included in this study. Mean (SD) follow-up time was 79 (35) months (range, 1-152 months). Biliary stricture was diagnosed in 84 patients (20.4%). Multivariate analysis indicated that postoperative biliary leakage (odd ratio [OR], 3.94; P = .001), acute cellular rejection (OR, 3.05; P < .001), donor age older than 47.5 years (OR, 2.05; P = .032), preoperative recipient platelet value < 77.5 × 10³/mL (OR, 1.91; P = .023), University of Wisconsin solution (OR, 1.73; P = .041)), recipient male sex (OR, 1.78; P = .072), portal/arterial flow ratio > 4 (OR, 1.76; P = .083), and intraoperative bleeding > 2850 mL (OR, 1.70; P = .053) were independent risk factors for biliary stricture regardless of the time of their appearance. Multiple risk factors for biliary stricture were determined in this study. Some of these risk factors are preventable, and implementation of strategies to eliminate some of those factors should reduce the development of post-transplant biliary stricture.     

Health-related Quality of Life After Pediatric Liver Transplant: Single-Center Experience in Chile

IntroductionOrthotopic liver transplantation is the treatment of choice for most terminal liver diseases in children. Currently, the improved survival of these patients is well documented, but their quality of life post-transplant is not described. In Chile, Hospital Luis Calvo Mackenna (HLCM) has performed pediatric liver transplantation in children from around the country since 1994. The aim of this study is to evaluate our patients' and parents' current quality of life.MethodsA cross-sectional study was conducted between July 2010 and June 2011. All liver transplant patients currently in control at HLCM were invited to complete the PedsQL 4.0 report (Pediatric Quality of Life Inventory). For each group, average score was calculated and comparisons were done using Student t and χ² tests.ResultsForty-nine patients were enrolled. One-third of the patients were between 2 and 4 years, one-third between 5 and 12, and the rest were 13 to 18 years old. Half of the patients had their transplants for more than 3 years, 53% were female, 53% lived in cities far from the transplant center, 72.5% had chronic liver disease, 53% had received a liver from cadaveric donor, and 21% had received more than 1 liver transplant. Patients under 4 years referred good health-related quality of life (HRQOL) in all categories. All school-age patients had poor or very poor psychosocial HRQOL.DiscussionOur good results obtained in transplant patients under 4 years may be because the questionnaire was completed by caregivers. The school-age patients were affected in terms of school functioning, as they were not able to participate in all the activities. These findings need to be compared with HRQOL perception in other groups, such as children with other chronic conditions, and evaluated with other broader factors, as reported in international HRQOL publications.     

Comparison of the Incidence of De Novo Malignancy in Liver or Kidney Transplant Recipients: Analysis of 2673 Consecutive Cases in a Single Center

Purpose

An increased incidence of de novo malignancy (dM) is an established complication among solid organ transplant (SOT) recipients compared with the general population. The aims of this study were to describe the incidence and cumulative risk for development of dM among our transplanted population, depending on various clinical and pathologic variables.

Methods

We retrospectively reviewed the medical records and pathologic data of SOT recipients performed from February 1995 to December 2010.

Results

Among 2673 consecutive SOT recipients, the dM that developed in 66 (2.5%) patients included, 16 (0.6%; 24.2% of overall dM) lymphoid dM and 50 (1.9%; 75.8% of overall dM) nonlymphoid dM. Cumulative incidence of dM in liver was significantly higher than that in kidney transplant recipients. A significantly higher cumulative incidence of dM was observed among living donor versus deceased donor SOT. Although the more frequent development of lymphoid dM was observed during the first year posttransplantation, the cumulative risk of nonlymphoid dM increased year by year, reaching a substantially higher incidence than that of lymphoid dM beyond 5 years after SOT. Comparing the various immunosuppressive regimens, the cumulative incidence was greater among the group with basiliximab induction. However, the hazard of occurrence was unaffected by whether tacrolimus or cyclosporine was used for maintenance immunosuppression. The increased risk of dM was not dependent on recipient age or gender.

Conclusion

This study demonstrated distinctive cumulative incidences of dM in different clinical and pathologic settings.     

Chemotherapy for De Novo Gastric Adenocarcinoma After Deceased Orthotopic Liver Transplantation: A Case Report

Background

De novo gastric cancer is a rare complication of liver transplantation.

Safety and Efficacy of a Steroid Avoidance Immunosuppression Regimen in Renal Transplant Patients With De Novo or Preformed Donor-Specific Antibodies: A Single-Center Study

Although interest in the role of donor-specific antibodies (DSAs) in kidney transplant rejection, graft survival, and histopathological outcomes is increasing, their impact on steroid avoidance or minimization in renal transplant populations is poorly understood. Primary outcomes of graft survival, rejection, and histopathological findings were assessed in 188 patients who received transplants between 2012 and 2015 at the Scripps Center for Organ Transplantation, which follows a steroid avoidance protocol. Analyses were performed using data from the United Network for Organ Sharing. Cohorts included kidney transplant recipients with de novo DSAs (dnDSAs; n = 27), preformed DSAs (pfDSAs; n = 15), and no DSAs (nDSAs; n = 146). Median time to dnDSA development (classes I and II) was shorter (102 days) than in previous studies. Rejection of any type was associated with DSAs to class I HLA (P < .05) and class II HLA (P < .01) but not with graft loss. Although mean fluorescence intensity (MFI) independently showed no association with rejection, an MFI >5000 showed a trend toward more antibody-mediated rejection (P < .06), though graft loss was not independently associated. Banff chronic allograft nephropathy scores and a modified chronic injury score were increased in the dnDSA cohort at 6 months, but not at 2 years (P < .001 and P < .08, respectively). Our data suggest that dnDSAs and pfDSAs impact short-term rejection rates but do not negatively impact graft survival or histopathological outcomes at 2 years. Periodic protocol post-transplant DSA monitoring may preemptively identify patients who develop dnDSAs who are at a higher risk for rejection.     

Protein Kinase C Inhibitor Sotrastaurin in De Novo Liver Transplant Recipients: A Randomized Phase II Trial

Efficacy and safety of protein kinase C inhibitor sotrastaurin (STN) with tacrolimus (TAC) was assessed in a 24‐month, multicenter, phase II study in de novo liver transplant recipients. A total of 204 patients were randomized (1:1:1:1) to STN 200 mg b.i.d. + standard‐exposure TAC (n = 50) or reduced‐exposure TAC (n = 52), STN 300 mg b.i.d. + reduced‐exposure TAC (n = 50), or mycophenolate mofetil (MMF) 1 g b.i.d. + standard‐exposure TAC (control, n = 52); all with steroids. Owing to premature study termination, treatment comparisons were only conducted for Month 6. At Month 6, composite efficacy failure rates (treated biopsy‐proven acute rejection episodes of Banff grade ≥1, graft loss, or death) were 25.0%, 16.5%, 20.9% and 15.9% for STN 200 mg + standard TAC, STN 200 mg + reduced TAC, STN 300 mg + reduced TAC and control groups, respectively. Median estimated glomerular filtration rates were 84.0, 83.3, 81.1 and 75.3 mL/min/1.73 m², respectively. Gastrointestinal events (constipation, diarrhea, and nausea), infection, and tachycardia were more frequent in STN groups. More patients in STN groups experienced serious adverse events compared with the control group (62.3–70.8% vs. 51.9%). STN‐based regimens were associated with a higher efficacy failure rate and higher incidence of adverse events with no significant difference in renal function between the groups.     

De Novo Malignancy Following Adult-to-Adult Living Donor Liver Transplantation Focusing on Posttransplantation Lymphoproliferative Disorder

Objective

In patients with living donor liver transplantation (LDLT), late-onset complications sometimes develop because of long-term use of immunosuppressive drugs. One of the immunosuppressive drug-related complications is de novo malignancies resulting in reduced survival.

Sirolimus in Liver Transplant Recipients: A Large Single-Center Experience

Sirolimus (SRL) is a newer immunosuppressant whose possible benefits and side effects in comparison to calcineurin inhibitors (CNIs) still have to be addressed in the liver transplantation setting. We report the results of the use of SRL in 86 liver transplant recipients, 38 of whom received SRL as the main immunosuppressant in a CNI-sparing regimen. Indications for the use of SRL were: impaired renal function (n = 32), CNI neurotoxicity (n = 16), hepatocellular carcinoma (HCC) at high risk of recurrence (n = 21), recurrence of HCC (n = 6), de novo malignancies (n = 4), cholangiocarcinoma (n = 1), and the need to reinforce immunosuppression (n = 6). Among patients on SRL-based treatment, four episodes of acute rejection were observed, three of which occurred during the first postoperative month. Renal function significantly improved when sirolimus was introduced within the third postoperative month, while no change was observed when it was introduced later. Neurological symptoms resolved completely in 14/16 patients. The 3-year recurrence-free survival of patients with HCC on SRL was 84%. Sixty-two patients developed side effects that required drug withdrawal in seven cases. There was a reduced prevalence of hypertension and new-onset diabetes among patients under SRL. In conclusion, SRL was an effective immunosuppressant even when used in a CNI-sparing regimen. It was beneficial for patients with recently developed renal dysfunction or neurological disorders.     

MeltDose Technology vs Once-Daily Prolonged Release Tacrolimus in De Novo Liver Transplant Recipients

BackgroundAn extended-release formulation of tacrolimus designed for once-daily administration (LCP-TAC) is a new prolonged-release tacrolimus (TAC-PR) formulation using a drug delivery technology designed to enhance the bioavailability of drugs compared with TAC-PR. The aim of this study was to retrospectively compare de novo administration of LCP-TAC and TAC-PR for therapeutic trough levels and daily dosage during the first 30 days after first liver transplant (LT).MethodsA total of 35 patients submitted to first LT between 2016 and 2018 were retrospectively enrolled: 16 received LCP-TAC, while 19 received TAC-PR as de novo immunosuppression. Patients were analyzed for daily dosage and trough levels at postoperative days (PODs) 3, 7, 15, and 30.ResultsThe initial dose of tacrolimus did not differ between LCP-TAC and TAC-PR (mean, 5.19 [SD, 1.72] mg/d vs mean, 5.26 [SD, 1.91] mg/d, P = .90). On PODs 7, 15, and 30 the daily dosage was statistically lower for LCP-TAC compared with TAC-PR (mean, 5.44 [SD, 2.06] mg/d vs mean, 7.68 [SD, 2.91] mg/d, P = .01; mean, 5.33 [SD, 2.23] mg/d vs mean, 8.82 [SD, 2.35] mg/d, P < .001; and mean, 5.38 [SD, 2.50] mg/d vs mean, 9.81 [SD, 3.78] mg/d, P < .001, respectively). The therapeutic trough levels were significantly higher for LCP-TAC on POD 3 (mean, 5.05 [SD, 3.58] ng/mL vs mean, 2.42 [SD, 2.75] ng/mL, P = .03) and POD 5 (mean, 7.35 [SD, 5.12] ng/mL vs mean, 4.17 [SD, 2.05] ng/mL, P = .04), while no differences were found on PODs 7, 15, and 30.The percentage of patients on POD 3 achieving a trough level higher than 6 ng/mL was higher for LCP-TAC than TAC-PR (40% vs 13%, P = .05).ConclusionsLCP-TAC after LT is safe and might enhance bioavailability, reducing the amount of drug necessary to achieve therapeutic trough levels compared with TAC-PR.     

Multiple Clinical Presentations of Lymphoproliferative Disorders in Pediatric Liver Transplant Recipients: A Single-Center Experience

Posttransplantation lymphoproliferative disorder (PTLD) is a serious complication following solid organ transplantation that has been linked to Epstein-Barr virus (EBV) infection. The aim of this article was to describe a single-center experience with the multiplicity of clinical presentations of PTLD. Among 350 liver transplantations performed in 303 children, 13 survivor children displayed a histological diagnosis of PTLD (13/242 survivors; 5.4%). The age at diagnosis ranged from 12 to 258 months (median, 47), and the time from transplantation ranged from 1 to 84 months (median, 13). Ten of these children (76.9%) were EBV-naïve prior to transplantation. Fever was present in all cases. The clinical signs at presentation were anemia (92.3%), diarrhea and vomiting (69.2%), recurrent upper airway infections (38.4%), Waldeyer ring lymphoid tissue hypertrophy (23.0%), abdominal mass lesions (30.7%), massive cervical and mediastinal adenopathy (15.3%), or gastrointestinal and respiratory symptoms (30.7%). One child developed fulminant hepatic allograft failure secondary to graft involvement by PTLD. Polymorphic PTLD was diagnosed in 6 patients; 7 had the diagnosis of lymphoma. Treatment consisted of stopping immunosuppression as well as starting intravenous gancyclovir and anti-CD20 monoclonal antibody therapy. The mortality rate was 53.8%. The clinical presentation of PTLD varied from fever of unknown origin to fulminant hepatic failure. The other symptoms that may be linked to the diagnosis of PTLD are pancytopenia, tonsil and adenoid hypertrophy, cervical or mediastinal lymph node enlargement, as well as abdominal masses. Despite numerous advances, the optimal treatment approach for PTLD is not completely known and the mortality rate is still high.     

Tacrolimus Monotherapy in Recipients of Liver Transplant: A Single-Center Experience

IntroductionFollowing liver transplantation (LT), the majority of patients are treated with reduced-dose calcineurin inhibitors (CNIs) in combination with mycophenolate mofetil. The optimal timing for subsequent conversion to CNI monotherapy is not clearly defined. This study aims to evaluate the safety of conversion to CNI monotherapy after LT.MethodsThis was a single-center retrospective study of 100 consecutive patients who received CNI and mycophenolate mofetil combination regimen after LT at Singapore General Hospital from 2006 to 2018. Patient demographics, clinical parameters, and posttransplant complications (ie, rates of graft rejection, de novo malignancy, cytomegalovirus infection and renal impairment) were recorded.ResultsOne hundred patients were recruited and mean follow-up time in months ± standard deviation was 60.36 ± 41.73. Patients were divided into 2 groups based on institution of CNI monotherapy within (group 1) or beyond (group 2) 6 months. Twenty-five (25%) patients were on CNI monotherapy within 6 months post-LT. Overall patient survival was 83.7% at 5-years posttransplant. There was no statistical difference in the rates of posttransplant complications including liver graft rejection (4.0% vs 18.7%, P = .11); de novo malignancy (0.0% vs 8.0%, P = .33); cytomegalovirus infection (4.0% vs 1.3%, P = .44); and renal impairment (20.0% vs 40.0%, P = .069) between the 2 groups.ConclusionsSuccessful institution of CNI monotherapy within 6 months is safe, and does not increase the risk of rejection.     

Everolimus With Reduced Tacrolimus Improves Renal Function in De Novo Liver Transplant Recipients: A Randomized Controlled Trial

In a prospective, multicenter, open‐label study, de novo liver transplant patients were randomized at day 30±5 to (i) everolimus initiation with tacrolimus elimination (TAC Elimination) (ii) everolimus initiation with reduced‐exposure tacrolimus (EVR+Reduced TAC) or (iii) standard‐exposure tacrolimus (TAC Control). Randomization to TAC Elimination was terminated prematurely due to a higher rate of treated biopsy‐proven acute rejection (tBPAR). EVR+Reduced TAC was noninferior to TAC Control for the primary efficacy endpoint (tBPAR, graft loss or death at 12 months posttransplantation): 6.7% versus 9.7% (?3.0%; 95% CI ?8.7, 2.6%; p<0.001 for noninferiority [12% margin]). tBPAR occurred in 2.9% of EVR+Reduced TAC patients versus 7.0% of TAC Controls (p = 0.035). The change in adjusted estimated GFR from randomization to month 12 was superior with EVR+Reduced TAC versus TAC Control (difference 8.50 mL/min/1.73 m², 97.5% CI 3.74, 13.27 mL/min/1.73 m², p<0.001 for superiority). Drug discontinuation for adverse events occurred in 25.7% of EVR+Reduced TAC and 14.1% of TAC Controls (relative risk 1.82, 95% CI 1.25, 2.66). Relative risk of serious infections between the EVR+Reduced TAC group versus TAC Controls was 1.76 (95% CI 1.03, 3.00). Everolimus facilitates early tacrolimus minimization with comparable efficacy and superior renal function, compared to a standard tacrolimus exposure regimen 12 months after liver transplantation.     

Ureteral Complications Requiring Intervention After Kidney Transplant: A Single-Center Experience

The surgical aspect of kidney transplant can be the surgical technique itself or the use of reconstruction techniques in the case of a complication requiring reoperation. In our study, we examined particularly surgical techniques and reconstruction options for ureteral anastomoses.Data from patients who underwent kidney transplant from 2010 to 2020 (N = 433) were examined retrospectively at follow-up of at least 1 year. We sought an association between the type of ureteral anastomoses and parameters considered to be risk factors based on literature data. We did not note the complicated cases that solved spontaneously and only selected cases where the ureteral anastomosis complication (UAcomp) needed urologic, radiological, or surgical intervention. In a smaller group, we examined the correlation between BK polyomavirus and ureteral stenosis.A total of 9.2% (n = 40) of patients developed UAcomp, 67.5% (n = 27) of whom required reoperation. In complicated cases, the rate of primary ureteral anastomosis type was 60.0% (n = 24) ureteroneocystostomy (UNS) and 40.0% (n = 16) ureteroureterostomy (UU) (P = .184). After UNS, 7.7% (n = 17) of cases required reoperation, and this rate was 4.7% (n = 10) after UU (P = .164). After treatment of the UAcomp, 95.0% (n = 38) of the patients were discharged with a functioning graft, and 5.0% (n = 2) required graftectomy.Complications of ureteral anastomosis with appropriate interventions results in good graft function. The type of ureteral anastomosis is not significantly associated with UAcomp. It is important that the operating surgeon is well versed in UNS and UU techniques to be able to adapt to any situation, be it primary surgery or reoperation.     

Risk Factors for De Novo Malignancy Following Lung Transplantation

Risk factors for non–skin cancer de novo malignancy (DNM) after lung transplantation have yet to be identified. We queried the United Network for Organ Sharing database for all adult lung transplant patients between 1989 and 2012. Standardized incidence ratios (SIRs) were computed by comparing the data to Surveillance, Epidemiology, and End Results Program data after excluding skin squamous/basal cell carcinomas. We identified 18 093 adult lung transplant patients; median follow‐up time was 1086 days (interquartile range 436–2070). DNMs occurred in 1306 patients, with incidences of 1.4%, 4.6%, and 7.9% at 1, 3, and 5 years, respectively. The overall cancer incidence was elevated compared with that of the general US population (SIR 3.26, 95% confidence interval [CI]: 2.95–3.60). The most common cancer types were lung cancer (26.2% of all malignancies, SIR 6.49, 95% CI: 5.04–8.45) and lymphoproliferative disease (20.0%, SIR 14.14, 95% CI: 9.45–22.04). Predictors of DNM following lung transplantation were age (hazard ratio [HR] 1.03, 95% CI: 1.02–1.05, p < 0.001), male gender (HR 1.20, 95% CI: 1.02–1.42, p = 0.03), disease etiology (not cystic fibrosis, idiopathic pulmonary fibrosis or interstitial lung disease, HR 0.59, 95% CI 0.37–0.97, p = 0.04) and single‐lung transplantation (HR 1.64, 95% CI: 1.34–2.01, p < 0.001). Significant interactions between donor or recipient smoking and single‐lung transplantation were noted. On multivariable survival analysis, DNMs were associated with an increased risk of mortality (HR 1.44, 95% CI: 1.10–1.88, p = 0.009).