Lung Retransplantation for Chronic Rejection: A Single-Center Experience

doi:10.1016/j.athoracsur.2017.07.025

The Annals of Thoracic Surgery

Volume 105, Issue 1, January 2018, Pages 221-227

Presented at the Fifty-third Annual Meeting of The Society of Thoracic Surgeons, Houston, TX, Jan 21–25, 2017.

https://doi.org/10.1016/j.athoracsur.2017.07.025 Get rights and content

Background

Chronic lung allograft dysfunction (CLAD) is nonreversible and remains the biggest obstacle to long-term survival after lung transplantation (LTx). Retransplantation is the sole definitive therapeutic option for CLAD. We analyzed our single-center experience with retransplantation as a treatment option for CLAD.

Methods

From March 1, 2010, to May 31, 2016, 419 consecutive patients underwent LTx at our institution; 29 of these procedures were retransplantations for CLAD. We analyzed demographic characteristics, lung allocation score, operation type, length of stay, and perioperative outcomes. Actuarial survival was estimated using Kaplan-Meier survival curves.

Results

In total, 29 of 419 patients (6.9%) underwent retransplantation for CLAD. Median time from primary LTx to retransplantation was 1,163 days (range: 304 to 3,971 days). Patients undergoing retransplantation were younger and had higher lung allocation scores than primary transplantation patients. Most LTx procedures were bilateral (93% of retransplantations, 95% of primary LTx). Rates of cardiopulmonary bypass, extracorporeal membrane oxygenation support for severe primary graft dysfunction, and re-exploration for bleeding were higher in retransplantation patients (p = 0.010, p = 0.019, and p = 0.029, respectively). One- and 5-year survival rates in the retransplantation group were similar to those of the primary LTx group (89.2% and 64.3% versus 89.7% and 58.2%, respectively; p = 0.79).

Conclusions

Lung retransplantation is a viable treatment option for CLAD after LTx. In this study, retransplantation patients were younger, had higher lung allocation scores, and were more likely to require cardiopulmonary bypass and postoperative extracorporeal membrane oxygenation support than primary LTx patients. Postoperative length of stay and short- and mid-term survival were comparable with those of primary LTx patients.

Section snippets

Study Population

This study was approved by the Institutional Review Board at St. Joseph’s Hospital and Medical Center. We reviewed the charts of patients who underwent LTx between March 1, 2010, and May 31, 2016, at Norton Thoracic Institute at St. Joseph’s Hospital and Medical Center in Phoenix, Arizona. All 419 patients who received LTx during this time period were included in the study. Patients were separated into one of two groups: primary LTx or lung retransplantation. Patient selection for primary LTx

Patient Characteristics

In total, 419 patients underwent LTx during the study period. Of these, 390 patients (93.1%) underwent primary LTx; 29 patients (6.9%) underwent retransplantation (Table 1). The indication for all 29 retransplantations was CLAD. Median time to retransplantation after initial LTx was 1,163 days (range: 304 to 3971 days). Most LTx procedures were bilateral—27 of 29 in the retransplantation group (93.1%) and 374 of 390 in the primary LTx group (95.9%). Patients who underwent retransplantation were

Comment

This report is a single-center review describing outcomes of lung retransplantation in 29 patients. Because of the reported poor outcomes after lung retransplantation for acute graft failure and airway complications 1, 3, 4, 9, we instituted a policy to perform retransplantation only for CLAD. The outcomes for lung retransplantation were then compared with the outcomes for primary LTx at our center.

Lung retransplantation procedures increased in frequency after the introduction of the LAS system

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Cited by (18)

Perioperative Outcomes During Double-Lung Transplantation and Retransplantation in Cystic Fibrosis Patients: A Monocentric Cohort Study
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Life expectancy for lung-transplant patients, especially those with cystic fibrosis (CF), is leading increasingly to more retransplantations.
Retrospective monocentric cohort study.
Foch University Hospital, Suresnes, France.
CF patients having had a primary double-lung transplantation (pLgTx) or a retransplantation (reLgTx) from 2012 to 2021.
None.
The authors compared the main intraoperative and early postoperative features between pLgTx (n = 258) and reLgTx (n = 24). Demographic characteristics were similar. No patients with retransplantations had a preoperative bridge with extracorporeal membrane oxygenation (ECMO); however, 23 patients had it in the pLgTx group (p = 0.24). Patients with retransplants had longer second graft ischemic time (p = 0.02), larger intraoperative bleeding volume (p = 0.001) and blood transfusion (p = 0.009 for packed red blood cells), increased blood lactate concentrations (p = 0.002), and higher norepinephrine dose at end-surgery (p = 0.001). Extracorporeal membrane oxygenation was used during surgery in 94 patients in the pLgTx group and 12 patients in the reLgTx group (p = 0.39). Extracorporeal membrane oxygenation could not be weaned after surgery in 55 patients in the pLgTx group and 4 in the reLgTx group (p = 0.54). Despite worse preoperative renal function in the reLgTx group (p < 0.001), there was no difference concerning renal replacement therapy in the intensive care unit between groups (p = 0.08). There were no differences between groups concerning the main complications, including primary graft dysfunction. Although the difference was not statistically different (p = 0.17), mortality was 3 times higher in the reLgTx group.
Intraoperative period of retransplantation was more convoluted but had a similar ECMO profile to primary transplantation. In addition, the early postoperative period was similar.
Identification of Lung Transplant Recipients With a Survival Benefit After Fundoplication
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Gastroesophageal reflux disease (GERD) and aspiration of enteric contents are associated with worse outcomes after lung transplantation. The purpose of this study was to elucidate populations of patients who benefit the most from fundoplication after lung transplantation.
Lung transplantations from 2001 to 2019 (n = 971) were retrospectively reviewed and stratified by fundoplication before (n = 128) or after (n = 24) chronic lung allograft dysfunction (CLAD) development vs patients who did not undergo fundoplication. Patients with a fundoplication before CLAD were propensity matched to patients without a fundoplication. The primary outcome of interest was posttransplant survival. Time-to-event rates were calculated using a multivariable Cox proportional hazards model and Kaplan-Meier functions.
Fundoplication before CLAD improved posttransplant survival before and after propensity matching, and it remained a significant predictor after adjusting for baseline characteristics (hazard ratio [HR],0.57; 95 % confidence interval [CI], 0.4 to 0.8; P = .001). Transplant recipients with a restrictive disorder (HR, 0.46; 95 % CI, 0.3 to 0.73; P = .001), age younger than 65 years (HR, 0.48; 95 % CI, 0.32 to 0.71; P < ;0.001), and with both single (HR, 0.47; 95 % CI, 0.28 to 0.79; P = .005) and double (HR, 0.55; 95 % CI, 0.32 to 0.93; P = .027) lung transplants had a significant decrease in mortality after fundoplication. The effect was present after excluding early deaths and CLAD diagnoses. Gastroesophageal reflux disease diagnosed by pH, impedance, or esophagogastroduodenoscopy was not associated with worse outcomes. Among patients with CLAD, a fundoplication was an independent predictor of post-CLAD survival (HR, 0.27; 95 % CI; 0.12 to 0.61; P = .002).
Fundoplication before or after CLAD development is an independent predictor of survival. Younger patients with restrictive disease, independent of the type of transplant, have a survival benefit. Gastroesophageal reflux disease diagnosed by conventional methods was not associated with worse survival.
Outcomes After Lung Retransplantation: A Single-Center Retrospective Cohort Study
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Citation Excerpt :
Additional factors that could explain the relationship between early LRT and worse survival must be sought in future studies. The trend toward decreased graft survival for the recipients who had LAS score >50 is not entirely surprising, and it corroborates with results from other studies.3,5 As a surrogate for severity of disease,16 higher LAS scores indicate sicker patients who may be more susceptible to complications from any major surgery including LRT.
One-Year Survival Worse for Lung Retransplants Relative to Primary Lung Transplants
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Outcomes after lung retransplantation (LRT) remain inferior compared with primary lung transplantation (PLT). This study examined the impact of center volume on 1-year survival after LRT.
Using the United Network for Organ Sharing database, the study abstracted patients undergoing PLT and LRT between January 2006 and December 2017, excluding combined heart-lung transplants and multiple retransplants. One-year survival rates after PLT and LRT were compared using propensity score matching. In the LRT cohort, multivariable Cox models with and without time-dependent coefficients were fitted to examine association between transplant center volume and 1-year survival. Center volume was categorized on the basis of inspection of restricted cubic splines.
A total of 20,675 recipients (PLT 19,853 [96.0%] vs LRT 822 [4.0%]) were included. One-year survival was lower for LRT recipients in the matched cohort (PLT 84.8% vs LRT 76.7%). There was steady improvement in 1-year survival after LRT (2006 to 2009 72.1% vs 2010 to 2013 76.6% vs 2014 to 2017 80.1%). Higher center volume was associated with better 1-year survival after LRT. This survival difference was noted in the initial 30 days after transplantation (intermediate vs low volume hazard ratio, 0.282 [95% confidence interval, 0.151 to 0.526]; high vs low volume hazard ratio, 0.406 [95% confidence interval, 0.224 to 0.737]), but it became insignificant after 30 days.
Superior 1-year survival after LRT at higher-volume centers is predominantly the result of better 30-day outcomes. This finding suggests that LRT candidates may be referred to higher-volume centers for surgery.
Consensus document for the selection of lung transplant candidates: An update from the International Society for Heart and Lung Transplantation
2021, Journal of Heart and Lung Transplantation
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The outcomes after re-transplants are inferior compared to first lung transplants, particularly if the re-transplant is done within the first year after the original transplant or for patients with restrictive allograft syndrome (RAS).1,139,140,145-149 Several studies, however, have found acceptable results for carefully selected recipients.140,146,150,151 In the pre-transplant evaluation of such patients, particular emphasis should be focused on understanding the possible reasons for the graft failure, such as alloimmunization, poor adherence, GER, or repeated infections.86,152
Tens of thousands of patients with advanced lung diseases may be eligible to be considered as potential candidates for lung transplant around the world each year. The timing of referral, evaluation, determination of candidacy, and listing of candidates continues to pose challenges and even ethical dilemmas. To address these challenges, the International Society for Heart and Lung Transplantation appointed an international group of members to review the literature, to consider recent advances in the management of advanced lung diseases, and to update prior consensus documents on the selection of lung transplant candidates. The purpose of this updated consensus document is to assist providers throughout the world who are caring for patients with pulmonary disease to identify potential candidates for lung transplant, to optimize the timing of the referral of these patients to lung transplant centers, and to provide transplant centers with a framework for evaluating and selecting candidates. In addition to addressing general considerations and providing disease specific recommendations for referral and listing, this updated consensus document includes an ethical framework, a recognition of the variability in acceptance of risk between transplant centers, and establishes a system to account for how a combination of risk factors may be taken into consideration in candidate selection for lung transplantation.
Lung retransplant. Experience of a referral centre
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El retrasplante pulmonar (RTP) es un tratamiento válido en pacientes con disfunción pulmonar, pero con una elevada morbimortalidad. Nuestro objetivo es analizar nuestra experiencia en RTP en supervivencia y función pulmonar.
Estudio retrospectivo de pacientes con RTP (1990-2019). Variables: receptores y procedimiento, mortalidad precoz, supervivencia y función pulmonar en pacientes CLAD. Variables cuantitativas (media±DE); cualitativas (%). Se utilizó el test t de Student o χ². La supervivencia se estimó mediante Kaplan-Meier, comparándose con Log Rank. Se estableció como significativa p < 0,05.
De 784 pacientes trasplantados, 25 pacientes (edad media 38,41 ± 16,3 años, 12 hombres y 13 mujeres) fueron RTP; CLAD (n = 19), infarto pulmonar (n = 2), complicaciones de vía aérea (n = 2), disfunción del injerto (n = 1), rechazo hiperagudo (n = 1). Tiempo medio hasta el retrasplante: 5,41 ± 3,87 años en CLAD y 21,2 ± 21,4 días en no CLAD.
La mortalidad a 90 días fue del 52% y 36,8% en el segundo periodo (p = 0,007), siendo mayor en pacientes que precisaron ECMO preoperatorio (80 vs. 20%, p = 0,04).
La supervivencia a 1 y 5 años fue del 53,9% y 37,7%, respectivamente (p = 0,016). La supervivencia del grupo CLAD fue mayor (p = 0,08). El ECMO pre RTP disminuyó la supervivencia (p = 0,032). FEV₁ mejoró una media de 0,98 ± 0,13L (25,6 ± 18,8%) (p = 0,001).
El RTP es un procedimiento de elevada mortalidad que obliga a una cuidadosa selección de los pacientes, con mejores resultados en aquellos con CLAD. La función pulmonar de los pacientes con CLAD mejoró significativamente.
Lung retransplantation (LR) is a valid choice with a significant risk of perioperative morbidity and mortality in selected patients with graft dysfunction after lung transplantation. Our goal is to analyse our experience in LR in terms of survival and lung function.
Retrospective study of patients undergoing LR (1990-2019). Variables: recipients and procedure, early mortality, survival and lung function in patients with CLAD. Quantitative variables (mean±SD); qualitative (%). Student's t test or χ2 was used. Survival was estimated using Kaplan-Meier, compared with Log Rank. A p < 0.05 was established as significant.
Of 784 transplanted patients, 25 patients (mean age 38.41-16.3 years, 12 men and 13 women) were LR; (CLAD (n = 19), pulmonary infarction (n = 2), airway complications (n = 2), graft dysfunction (n = 1), hyperacute rejection (n = 1), mean time to retransplantation: 5.41 ± 3.87 years in CLAD and 21.2 ± 21.4 days in non-CLAD.
The 90-day mortality was 52% and 36.8% in the second period (p = 0.007), being higher in patients who required preoperative ECMO (80 vs. 20%, p = 0.04).
The 1- and 5-year survival was 53.9% and 37.7%, respectively (p = 0.016). Survival of the CLAD group was greater (p = 0.08). Pre LR ECMO decreased survival (p = 0.032).
After LR, FEV₁ improved an average of 0.98 ± 0.13L (25.6 ± 18.8%) (p = 0.001).
LR is a high mortality procedure that requires careful selection of patients with better results in patients with CLAD. The lung function of patients with CLAD improved significantly.

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Original articleGeneral thoracicLung Retransplantation for Chronic Rejection: A Single-Center Experience

Background

Methods

Results

Conclusions

Section snippets

Study Population

Patient Characteristics

Comment

J Heart Lung Transplant

Clin Chest Med

J Thorac Cardiovasc Surg

J Heart Lung Transplant

J Heart Lung Transplant

J Thorac Cardiovasc Surg

Ann Thorac Surg

Ann Thorac Surg

Ann Thorac Surg

J Thorac Cardiovasc Surg

Chest

Ann Thorac Surg

Semin Thorac Cardiovasc Surg

Am J Transplant

Original article
General thoracic
Lung Retransplantation for Chronic Rejection: A Single-Center Experience