Survival After Lung Retransplantation in the United States in the Current Era (2004 to 2013): Better or Worse? Mathew Thomas, MD, Erol V. Belli, MD, Bhupendra Rawal, MS, Richard C. Agnew, MD, and Kevin P. Landolfo, MD Division of Cardiothoracic Surgery and Division of Biostatistics and Bioinformatics at Mayo Clinic, Mayo Clinic, Jacksonville, Florida
Background. To understand the current patient survival after lung retransplantation (LRTx) in the United States, which has historically been worse compared with primary lung transplantation (LPTx). Methods. The United Network for Organ Sharing (UNOS) registry was retrospectively analyzed to determine survival after adult LRTx performed in 604 (2.48%) of 14,850 patients from 2004 to 2013. After exclusions, 582 LRTx and 13,673 LPTx recipients were selected for analysis. Cox proportional hazards regression models were used to determine the prognosticators of survival after LRTx. Survival after LRTx and LPTx were compared using Kaplan-Meier analysis. Results. The median survival after LRTx was 2.6 years compared with 5.6 years after LPTx. One-year, 3-year, and 5-year survival rates were, respectively, 71.1%, 46.3%, and 34.5% for LRTx, and 84.3%, 66.5%, and 53.3% for LPTx (p < 0.001). On multivariate analysis, patients who had LRTx after a greater than 1-year interval survived longer (relative risk [RR] 0.53; 95% confidence interval [CI] 0.34% to 0.88%; p [ 0.008). Lower survival was associated with single-lung transplantations (RR 1.49; 95% CI, 1.06%
to 2.07%]; p [ 0.021), transplantations done between 2009 and 2013 (RR 1.40; CI, 1.01% to 1.94%; p [ 0.041), multiple (>1) retransplantations (RR 2.55; 95% CI, 1.14% to 5.72%; p [ 0.023), and recipients requiring pretransplantation ventilator support. The only significant donor variable for poor survival was death due to cerebrovascular accidents (RR 1.98; 95% CI, 1.23% to 3.18%; p [ 0.004). Conclusions. Patient survival after LRTx in the United States has improved compared with historical data but remains lower than LPTx. Careful recipient selection and preoperative optimization based on the factors identified in our study may help utilize resources better and improve survival after LRTx. Bilateral LRTx should be preferentially performed as much as possible. Poor candidates for LRTx include those requiring retransplantations more than once or within 1 year. Prospective multi-institutional studies are necessary to help better understand the actual role of these factors in LRTx.
T
survival was observed in LRTx performed for acute primary graft failure and airway dehiscence [9, 10]. Preoperative ventilator support requirements and functional status of the recipient, time to retransplantation, and institution case-volume have been reported as factors that influence the overall survival after LRTx [5–7, 11]. Due to the reported poor outcomes after LRTx, ethical and philosophic debates continue about its appropriateness in a limited-resource situation [12, 13]. Proper recipient selection has been suggested as a way to improve outcomes after LRTx [10]. There are sparse data regarding the current survival after LRTx performed in the United States. We analyzed data from the United Network for Organ Sharing (UNOS) database from 2004 to 2013 in order to understand the most recent trends in the overall survival and the factors that predict survival after adult LRTx in the United States.
he survival rates for primary lung transplantation (LPTx) have historically been among the lowest for all solid organ transplants, estimated at 80% for 1 year and 52% for 5 years [1, 2]. The 1-year and 5-year graft survival rates after LPTx were previously reported to be around 76% to 80% and 42% to 51%, respectively [3], with bronchiolitis obliterans being the most common cause of chronic failure [4]. Due to advances in immunosuppression, perioperative care, and operative techniques, both overall patient and graft survival rates for LPTx have shown improvement over time [2]. Lung retransplantation (LRTx) remains the only option for severe graft dysfunction in the acute and chronic settings but has reported survival rates that are much lower than LPTx. One-year patient survival rates after LRTx were previously reported to be around 45% to 50% [5–9]. The lowest
(Ann Thorac Surg 2015;-:-–-) Ó 2015 by The Society of Thoracic Surgeons
Accepted for publication April 7, 2015. Presented at the Poster Session of the Fifty-first Annual Meeting of The Society of Thoracic Surgeons, San Diego, CA, Jan 24–28, 2015.
Material and Methods
Address correspondence to Dr Thomas, Division of Cardiothoracic Surgery, Mayo Clinic, 4500 San Pablo Rd, Jacksonville, FL 32224; e-mail: [email protected].
The UNOS database is a prospective registry that includes data voluntarily submitted by transplantation centers in the United States. We conducted a
Ó 2015 by The Society of Thoracic Surgeons Published by Elsevier
0003-4975/$36.00 http://dx.doi.org/10.1016/j.athoracsur.2015.04.036
2
THOMAS ET AL SURVIVAL AFTER LRTX IN THE US
Ann Thorac Surg 2015;-:-–-
retrospective analysis of the UNOS registry data of adult (18 years of age) lung transplantations that occurred from 2004 to 2013. During the study period, a total of 14,850 patients underwent lung transplantation, of which 604 (2.46%) underwent LRTx. After excluding those with multiple missing data, heart-lung transplants, and duplicated entries, 13,673 LPTx and 582 LRTx adult recipients were selected for analysis. The donor variables analyzed included age, sex, presence of pulmonary infection, cigarette use, and mechanism of the death of the donor. Recipient variables included age, sex, preoperative body mass index (BMI), ventilator or extracorporeal membrane oxygenation (ECMO) support requirement prior to surgery, number of previous transplants, lung allocation score (LAS), indication for LRTx, smoking history, and time interval between subsequent transplantations (3 years). Transplant surgery variables included the type of transplantation (single versus double) and ischemic time. The Mayo Clinic Institutional Review Board approved the study.
Statistical Analysis The baseline recipient, donor, and surgical characteristics were initially compared between the 2 cohorts of LRTx and LPTx. Continuous variables are summarized with the sample median and range; categoric variables are summarized with number and percentage. One-year and 5-year overall survival rates after lung transplantation were the primary outcomes analyzed using the Kaplan-Meier method. A single-variable Cox
proportional hazards regression model was used to evaluate associations of recipient and donor characteristics with overall survival after LRTx. Multivariable Cox proportional hazards regression models were used to assess whether any significant association of recipient and donor characteristics was still present while controlling for other confounding variables. The Cox models estimated the relative risks (RRs), p values, and 95% confidence intervals (CIs). No adjustment for multiple testing was made in these exploratory analyses, and p values 0.05 or less were considered statistically significant. Statistical analysis was performed using SAS (version 9.2; SAS Institute, Inc, Cary, NC) and R Statistical Software (version 2.14.0; R Foundation for Statistical Computing, Vienna, Austria).
Results Baseline Characteristics for LRTx and LPTx Cohorts There were a number of significant differences noted between the LRTx and LPTx recipients (Table 1). In general, patients who underwent LRTx (median age, 49 years; range, 18 to 74 years) were younger than LPTx recipients (median age, 58 years; range, 18 to 81 years; p < 0.001). There were a higher proportion of female recipients who underwent LRTx compared with LPTx (48.3% vs 51.7%, p ¼ 0.002). The LRTx cohort had worse preoperative nutritional status, as indicated by the lower preoperative BMI and serum albumin levels. The LAS scores and ECMO or ventilator support requirements, used as surrogate measures for functional status and
Table 1. Recipient and Donor Characteristics Lung Retransplantation (n ¼ 582)
Variables Recipient variables Age at surgery (years) Sex (male) Initial BMI Serum total albumin ECMO prior to surgery Ventilator prior to surgery Donor variables Donor age (years) Donor sex (male) Left ventricular ejection fraction of donor heart Donor pulmonary infection confirmed Operative variables Ischemic time (hours) Type of transplantation Single Double
Primary Lung Transplantation (n ¼ 13,673)
p Value
49 301 22.4 3.7 26 123
(18–74) (51.7%) (12.5–35.9) (0.7–5.1) (4.5%) (21.1%)
58 7985 25.4 4.0 56 742
(18–81) (58.4%) (10.5–45.7) (0.5–9.3) (0.41%) (5.4%)
Background. To understand the current patient survival after lung retransplantation (LRTx) in the United States, which has historically been worse compared with primary lung transplantation (LPTx). Methods. The United Network for Organ Sharing (UNOS) registry was retrospectively analyzed to determine survival after adult LRTx performed in 604 (2.48%) of 14,850 patients from 2004 to 2013. After exclusions, 582 LRTx and 13,673 LPTx recipients were selected for analysis. Cox proportional hazards regression models were used to determine the prognosticators of survival after LRTx. Survival after LRTx and LPTx were compared using Kaplan-Meier analysis. Results. The median survival after LRTx was 2.6 years compared with 5.6 years after LPTx. One-year, 3-year, and 5-year survival rates were, respectively, 71.1%, 46.3%, and 34.5% for LRTx, and 84.3%, 66.5%, and 53.3% for LPTx (p < 0.001). On multivariate analysis, patients who had LRTx after a greater than 1-year interval survived longer (relative risk [RR] 0.53; 95% confidence interval [CI] 0.34% to 0.88%; p [ 0.008). Lower survival was associated with single-lung transplantations (RR 1.49; 95% CI, 1.06%
to 2.07%]; p [ 0.021), transplantations done between 2009 and 2013 (RR 1.40; CI, 1.01% to 1.94%; p [ 0.041), multiple (>1) retransplantations (RR 2.55; 95% CI, 1.14% to 5.72%; p [ 0.023), and recipients requiring pretransplantation ventilator support. The only significant donor variable for poor survival was death due to cerebrovascular accidents (RR 1.98; 95% CI, 1.23% to 3.18%; p [ 0.004). Conclusions. Patient survival after LRTx in the United States has improved compared with historical data but remains lower than LPTx. Careful recipient selection and preoperative optimization based on the factors identified in our study may help utilize resources better and improve survival after LRTx. Bilateral LRTx should be preferentially performed as much as possible. Poor candidates for LRTx include those requiring retransplantations more than once or within 1 year. Prospective multi-institutional studies are necessary to help better understand the actual role of these factors in LRTx.
T
survival was observed in LRTx performed for acute primary graft failure and airway dehiscence [9, 10]. Preoperative ventilator support requirements and functional status of the recipient, time to retransplantation, and institution case-volume have been reported as factors that influence the overall survival after LRTx [5–7, 11]. Due to the reported poor outcomes after LRTx, ethical and philosophic debates continue about its appropriateness in a limited-resource situation [12, 13]. Proper recipient selection has been suggested as a way to improve outcomes after LRTx [10]. There are sparse data regarding the current survival after LRTx performed in the United States. We analyzed data from the United Network for Organ Sharing (UNOS) database from 2004 to 2013 in order to understand the most recent trends in the overall survival and the factors that predict survival after adult LRTx in the United States.
he survival rates for primary lung transplantation (LPTx) have historically been among the lowest for all solid organ transplants, estimated at 80% for 1 year and 52% for 5 years [1, 2]. The 1-year and 5-year graft survival rates after LPTx were previously reported to be around 76% to 80% and 42% to 51%, respectively [3], with bronchiolitis obliterans being the most common cause of chronic failure [4]. Due to advances in immunosuppression, perioperative care, and operative techniques, both overall patient and graft survival rates for LPTx have shown improvement over time [2]. Lung retransplantation (LRTx) remains the only option for severe graft dysfunction in the acute and chronic settings but has reported survival rates that are much lower than LPTx. One-year patient survival rates after LRTx were previously reported to be around 45% to 50% [5–9]. The lowest
(Ann Thorac Surg 2015;-:-–-) Ó 2015 by The Society of Thoracic Surgeons
Accepted for publication April 7, 2015. Presented at the Poster Session of the Fifty-first Annual Meeting of The Society of Thoracic Surgeons, San Diego, CA, Jan 24–28, 2015.
Material and Methods
Address correspondence to Dr Thomas, Division of Cardiothoracic Surgery, Mayo Clinic, 4500 San Pablo Rd, Jacksonville, FL 32224; e-mail: [email protected].
The UNOS database is a prospective registry that includes data voluntarily submitted by transplantation centers in the United States. We conducted a
Ó 2015 by The Society of Thoracic Surgeons Published by Elsevier
0003-4975/$36.00 http://dx.doi.org/10.1016/j.athoracsur.2015.04.036
2
THOMAS ET AL SURVIVAL AFTER LRTX IN THE US
Ann Thorac Surg 2015;-:-–-
retrospective analysis of the UNOS registry data of adult (18 years of age) lung transplantations that occurred from 2004 to 2013. During the study period, a total of 14,850 patients underwent lung transplantation, of which 604 (2.46%) underwent LRTx. After excluding those with multiple missing data, heart-lung transplants, and duplicated entries, 13,673 LPTx and 582 LRTx adult recipients were selected for analysis. The donor variables analyzed included age, sex, presence of pulmonary infection, cigarette use, and mechanism of the death of the donor. Recipient variables included age, sex, preoperative body mass index (BMI), ventilator or extracorporeal membrane oxygenation (ECMO) support requirement prior to surgery, number of previous transplants, lung allocation score (LAS), indication for LRTx, smoking history, and time interval between subsequent transplantations (3 years). Transplant surgery variables included the type of transplantation (single versus double) and ischemic time. The Mayo Clinic Institutional Review Board approved the study.
Statistical Analysis The baseline recipient, donor, and surgical characteristics were initially compared between the 2 cohorts of LRTx and LPTx. Continuous variables are summarized with the sample median and range; categoric variables are summarized with number and percentage. One-year and 5-year overall survival rates after lung transplantation were the primary outcomes analyzed using the Kaplan-Meier method. A single-variable Cox
proportional hazards regression model was used to evaluate associations of recipient and donor characteristics with overall survival after LRTx. Multivariable Cox proportional hazards regression models were used to assess whether any significant association of recipient and donor characteristics was still present while controlling for other confounding variables. The Cox models estimated the relative risks (RRs), p values, and 95% confidence intervals (CIs). No adjustment for multiple testing was made in these exploratory analyses, and p values 0.05 or less were considered statistically significant. Statistical analysis was performed using SAS (version 9.2; SAS Institute, Inc, Cary, NC) and R Statistical Software (version 2.14.0; R Foundation for Statistical Computing, Vienna, Austria).
Results Baseline Characteristics for LRTx and LPTx Cohorts There were a number of significant differences noted between the LRTx and LPTx recipients (Table 1). In general, patients who underwent LRTx (median age, 49 years; range, 18 to 74 years) were younger than LPTx recipients (median age, 58 years; range, 18 to 81 years; p < 0.001). There were a higher proportion of female recipients who underwent LRTx compared with LPTx (48.3% vs 51.7%, p ¼ 0.002). The LRTx cohort had worse preoperative nutritional status, as indicated by the lower preoperative BMI and serum albumin levels. The LAS scores and ECMO or ventilator support requirements, used as surrogate measures for functional status and
Table 1. Recipient and Donor Characteristics Lung Retransplantation (n ¼ 582)
Variables Recipient variables Age at surgery (years) Sex (male) Initial BMI Serum total albumin ECMO prior to surgery Ventilator prior to surgery Donor variables Donor age (years) Donor sex (male) Left ventricular ejection fraction of donor heart Donor pulmonary infection confirmed Operative variables Ischemic time (hours) Type of transplantation Single Double
Primary Lung Transplantation (n ¼ 13,673)
p Value
49 301 22.4 3.7 26 123
(18–74) (51.7%) (12.5–35.9) (0.7–5.1) (4.5%) (21.1%)
58 7985 25.4 4.0 56 742
(18–81) (58.4%) (10.5–45.7) (0.5–9.3) (0.41%) (5.4%)
