Original Thoracic
Evaluation of Short-Term Outcome after Lung Transplantation in the Lung Allocation Score Era Nikolaus Kneidinger1 Julia Holzborn2 Stephan Czerner3 Hauke Winter4 Claus Neurohr1 René Schramm2 1 Department of Internal Medicine V, Comprehensive Pneumology
Center, Member of the German Center for Lung Research, University of Munich, Munich, Germany 2 Department of Cardiac Surgery, University of Munich, Munich, Germany 3 Department of Anesthesiology, University of Munich, Munich, Germany 4 Department of Thoracic Surgery, University of Munich, Munich, Germany
Thomas Weig3
Jürgen Behr1
Address for correspondence René Schramm, MD, PhD, Department of Cardiac Surgery, University of Munich, Marchioninistrasse 15, Munich 81377, Germany (e-mail: [email protected]).
Abstract
Keywords
► ► ► ►
lung allocation score LAS lung transplantation transplant benefit
Background In December 2011, the Eurotransplant Foundation (Leiden, The Netherlands) changed the allocation system for donor lungs from a model based on urgency and waiting time to the lung allocation score (LAS). Objective The aim of the study was to investigate the effects of the LAS implementation on the early outcome after lung transplantation in Germany. Methods We therefore retrospectively studied the outcome of the last 50 patients transplanted before and the first 50 patients transplanted after LAS implementation. Results Both patient groups were comparable in baseline characteristics at the time of transplantation. Postoperative hospital stays were comparable between the groups, that is, 40.3 26.8 and 40.3 31.3 days (p ¼ 0.992). Also, survival rates on intensive care, during entire hospital stay, at 90 days, 6 month, and 1 year after transplant were comparable between the groups. The retrospectively calculated LASs of the patients transplanted under the old allocation system were not statistically significantly different from those after LAS implementation, that is, 46.5 14.2 and 51.2 17.4 (p ¼ 0.139). Conclusion We demonstrate, for the first time, that implementation of the LAS in Germany had no negative effect on the early outcome after lung transplantation. Our data indicate that patients transplanted before implementation of the LAS had a similar prospective transplant benefit.
Introduction Lung transplantation is a well-established procedure in the treatment of end-stage lung disease. Careful patient selection, modern operative techniques, and immunosuppression, as well as dedicated postoperative surveillance in experienced transplant centers provide 5-year survival rates of approximately 60%.1 The threatening shortage of donor organs
received April 18, 2014 accepted after revision July 3, 2014
requires implementation of waiting lists and establishment of allocation models. Until December 2011, donor lungs were allocated in Germany upon matching size and blood group to the patient with the highest urgency status and waiting time.2 This allocation model however neglected the prospective transplantation benefit, which is demanded by the German legislation for organ transplantation. Therefore, the Eurotransplant
© Georg Thieme Verlag KG Stuttgart · New York
DOI http://dx.doi.org/ 10.1055/s-0034-1387821. ISSN 0171-6425.
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Thorac Cardiovasc Surg
Foundation (Leiden, The Netherlands) adopted the lung allocation score (LAS) for the allocation of donor lungs in Germany on December 10, 2011. Provided matching size and blood group, the LAS allocates an organ package to the patient with the highest estimated medical urgency before transplantation and the probability of success after transplantation, to give priority to candidates who are most urgently in need of a transplant and who are expected to receive the greatest benefit.3 In the United States, the LAS was implemented in 2005, until then donor lungs had been allocated upon waiting times only. The implementation of the LAS led to a reduction of waiting list mortality in the United States.4 A similar trend could be observed in a single center study of the waiting list behavior after implementation of the LAS in our center and was recently confirmed by a Germany-wide analysis.5,6 Whether or not the implementation of the LAS has an effect on the outcome after lung transplantation in Germany remains unknown so far.
Materials and Methods Study Design This study was conducted at the Munich Transplant Center, Ludwig-Maximilians-University, Munich, Germany. In a retrospective data analysis, the early results after lung transplantation of the last 50 patients transplanted before and the first 50 patients transplanted after implementation of the LAS were compared. The Munich Lung Transplant Group (MLTG) is an institutional interdisciplinary conference consisting of designated pneumologists, cardiac and thoracic surgeons, anesthesiologists, and intensive care medicine specialists of the LudwigMaximilians-University, Munich, as well as dedicated representatives of associated and cooperating teaching hospitals and clinics. MLTG conference meetings have been held before and after implementation of the LAS every 2 weeks. It is the indented goal of the MLTG conference to regularly evaluate end-stage lung disease patients, who eventually require transplantation, and to follow up on already transplanted patients. The MLTG decides in consent of representatives of all involved disciplines to list an individual patient for lung transplantation upon the current Eurotransplant guidelines.2
Allocation Models All transplanted MLTG patients received donor lungs allocated by the Eurotransplant foundation. Until December 10, donor lungs were allocated within three distinct urgency levels, that is, transplantable (“T”), urgent (“U”), and high urgent (“HU”). Provided matching size and blood group, the organ package was allocated to the patient with the highest urgency status and waiting time. The MLTG requested “U” or “HU” status at Eurotransplant on an individual basis, which was reviewed by three external experts in an anonymous fashion. Criteria for the “U” and “HU” status had been defined by the Eurotransplant members.2 Patients with “U” and “HU” status had to be reevaluated every 4 and 2 weeks, respectively, and required intensive care unit (ICU) treatment was mandatory. Thoracic and Cardiovascular Surgeon
Kneidinger et al.
On December 10, 2011, Eurotransplant replaced the allocation system for lungs in Germany by the LAS. Since then, donor lungs were allocated to the waiting patient with the highest LAS. LASs were generated with the Web-based calculator by Eurotransplant (www.eurotransplant.org). Detailed description of how the LAS is calculated has been previously published.7 The listing status of patients with a LAS 50 (high LAS) and a LAS < 50 (low LAS) have to be updated every 14 and 90 days, respectively. The collected data need to be not older than 1 month and 7 days in low and high LAS patients, respectively. In individual cases, a transplant center may request an exceptional LAS (eLAS), when the regularly calculated LAS is thought to not adequately mirror the clinical status of the individual patient.7 An eLAS request is anonymously reviewed by an expert board and conditional value higher than calculated may be granted. Children below the age of 12 years are listed with LAS of 100 automatically. To better compare the clinical status of the two patient groups, we retrospectively calculated the LAS for those patients transplanted before implementation of the LAS on December 10, 2011. These calculations were based on the individual “U” and “HU” request data. For patients transplanted in the “T” status, we used the last data before transplant. Missing data and data older than 4 weeks before transplant were replaced by physiological values according to Eurotransplant. During the entire observation period, lungs were also transplanted after rescue allocation as competitive organ offers, irrespective of the urgency status or LAS.2 Organs may be offered by Eurotransplant in a competitive fashion to participating lung transplant centers in case of an impending loss of the organ package to maximize organ placement if a donor lung has been declined on at least three occasions or if organ loss is expected due to unstable donor conditions. The individual transplant center may then transplant the best matching patient on the waiting list.
Parameters The demographic patient data at the time of transplantation were collected from the patient files and included age, gender, body mass index, transplantation mode [single lung transplantation (SLTx) or double lung transplantation (DLTx)], and the underlying indicative lung disease. Underlying diseases were summarized in interstitial lung disease (ILD; idiopathic pulmonary fibrosis, nonspecific interstitial pneumonia, cryptogenic pneumonia, hypersensitivity pneumonitis, fibrosis secondary to connective tissue disease); chronic obstructive pulmonary disease (COPD; emphysema, α-1-antitrypsin deficiency); cystic fibrosis (CF); retransplantation; and others (pulmonary hypertension, bronchiectases, sarcoidosis, lymphangioleiomyomatosis). Donor-specific data were recruited from the donation reports provided by Eurotransplant. Postoperative end points were durations of ICU and total hospital stays, as well as ICU, hospital, 90-day, 6-month, and 1-year survival. All 100 transplanted patients were retrospectively followed up for 1 year.
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Outcome after Lung Transplantation in the Lung Allocation Score Era
Statistics Data are given as mean values standard deviation and n represents the number of patients per group. The SPSS Statistics 20.0 (Armonk, New York, United States) software package was used to calculate differences between groups utilizing the Mann–Whitney U test for continuous variables and Chi-square test for categorical variables. A value of probability of less than 0.05 was defined to indicate statistical significance. ICU and hospital stays were censored for nonsurvivors.
Results The 100 patients were transplanted by the MLTG between January 29, 2011, and July 17, 2012. The first consecutive 50 patients were transplanted within 310 days and the second consecutive 50 patients within 216 days. Both patient groups, that is, patients transplanted before and after LAS implementation, were comparable in demographic data and frequencies of transplantation mode (SLTx and DLTx) and underlying diagnoses (►Table 1). Analyses of the donor data revealed that more lungs explanted from male donors were transplanted after LAS implementation (►Table 2). In addition, the mean PO2 at 100% oxygen ventilation was significantly lower in lungs transplanted after LAS implementation (►Table 2). Before LAS implementation, the MLTG transplanted 7 patients in “T”, 5 patients in “U”, and 38 patients in “HU”
Kneidinger et al.
status. The retrospectively calculated mean LAS was 46.5 14.2 (AU) in the 50 patients transplanted just before December 10, 2011. Of these, 40 patients (80%) had a retrospective LAS < 50, while 10 patients (20%) had a high LAS 50. Of the 50 patients transplanted under the LAS-based allocation system, 34 patients (68%) had a LAS < 50, while 16 patients (32%) had a LAS 50. Out of the latter, one child below the age of 12 years was listed with a LAS ¼ 100. One patient was granted an eLAS of 48. The mean LAS after December 10, 2011, was 51.2 17.4 (AU). Statistical comparison showed no significant difference between mean LASs before and after LAS implementation (p ¼ 0.139). Transplanted patients were listed 410 485 days before and 257 469 days after LAS implementation (p ¼ 0.112). Short-term survival after lung transplantation was comparable before and after LAS implementation (►Table 3). Hospital, 90-day, 6-month, and 1-year survival were not significantly different between the two patient groups (►Table 3). There was also no statistically significant difference in the 1-year survival rates before and after LAS implementation comparing distinct disease entities, that is, ILD, COPD, and CF (►Table 3). Differentiated analyses of the 1-year survival rates after retransplantation and due to other diagnosis were omitted due to the small number of patients and heterogenic diagnoses.
Table 1 Baseline characteristics of patients before and after implementation of the lung allocation scores p value
Pre-LAS (n ¼ 50)
Post-LAS (n ¼ 50)
Age (y)
49.9 13.4
46.1 14.2
0.175
Gender; female, n (%)
22 (44)
25 (50)
0.552
BMI (kg/m2)
22.5 4.5
21.2 3.6
0.108
A
26 (52)
18 (36)
0.106
B
16 (32)
16 (32)
0.999
AB
1 (2)
5 (10)
0.091
O
7 (14)
11 (22)
0.300
35 (70)
38 (76)
0.503
22 (44)
16 (32)
0.218
COPD/emphysema
8 (16)
15 (30)
0.095
Cystic fibrosis
8 (16)
9 (18)
0.792
Others
8 (16)
9 (18)
0.792
Retransplantation
Blood group, n (%)
DLTx, n (%) Diagnosis, n (%) Interstitial lung disease
4 (8)
1 (2)
0.169
Invasive ventilation before transplantation, n (%)
2 (4)
4 (8)
0.837
ECMO/ILA before transplantation, n (%)
2/0 (4)
2/2 (8)
0.837
Children < 12 y, n (%)
0 (0)
1 (2)
–
Abbreviations: BMI, body mass index; COPD, chronic obstructive pulmonary disease; DLTx, double lung transplantation; ECMO, extracorporeal membrane oxygenation; ILA, interventional lung assist. Note: Mean standard deviation. Thoracic and Cardiovascular Surgeon
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Outcome after Lung Transplantation in the Lung Allocation Score Era
Outcome after Lung Transplantation in the Lung Allocation Score Era
Kneidinger et al.
Table 2 Donor characteristics before and after implementation of the lung allocation scores Pre-LAS (n ¼ 50)
Post-LAS (n ¼ 50)
p value
Age (y)
46.9 14.6
44.8 13.7
0.450
Gender; female, n (%)
27 (54)
14 (28)
0.007
BMI
24.4 3.7
25.1 3.4
0.108
Mechanical ventilation (h)
84.5 87.9
76.7 76.4
0.639
Blood gas analysis (FIO2 100%) PO2 (mmHg)
481 61
452 75
0.041
PCO2 (mmHg)
39.5 8.2
40.1 12.5
0.777
PEEP (mbar)
6.4 1.8
6.5 1.9
0.808
The durations of ICU and total hospital stays were statistically not significantly different comparing transplanted patients before and after LAS implementation (►Table 3). In line with this, there were no relevant differences between the groups when comparing ICU and hospital stays before and after LAS implementation in a disease-specific fashion (►Table 3). The frequency of acceptance of competitive organ offers was 8 (16%) before and 9 (18%) after LAS implementation
(p ¼ 0.793). Out of these, three patients were transplanted for ILD, two patients were transplanted for COPD, and three patients were transplanted for CF before December 10, 2011. Under the new LAS system, eight competitive organ offers were accepted for COPD patients and one for others. Because competitive organ offers are allocated outside the “T”, “U”, “HU”, status and LAS, separate calculations excluding these patients were performed. However, there were no significant differences in ICU and hospital stays or survival
Table 3 Posttransplant outcome before and after implementation of the lung allocation scores Pre-LAS (n ¼ 50)
Post-LAS (n ¼ 50)
p value
19.8 24.4
21.7 29.5
0.734
Length of stay Intensive care unit (d SD) ILD
25.5 34.1
26.4 27.1
0.928
COPD
9.0 8.8
12.0 14.6
0.602
CF
16.5 11.1
13.2 14.1
0.606
40.3 26.8
40.3 31.3
0.992
Hospital (d SD) ILD
45.9 37.1
44.9 32.8
0.930
COPD
32.8 10.1
35.2 25.1
0.796
CF
41.0 19.2
28.6 11.6
0.123
Intensive care unit
90 (45)
94 (47)
0.464
Hospital
90 (45)
92 (46)
0.729
90 d
94 (47)
94 (47)
0.999
6 mo
86 (43)
88 (44)
0.768
1y
78 (39)
86 (43)
0.300
64 (14)
75 (12)
0.473
Survival, % (n)
ILD, % (n) COPD, % (n)
100 (8)
100 (15)
> 0.999
CF, % (n)
88 (7)
100 (9)
0.329
Abbreviations: CF, cystic fibrosis; COPD, chronic obstructive pulmonary disease; ILD, interstitial lung disease. Note: Mean standard deviation. Thoracic and Cardiovascular Surgeon
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Abbreviations: BMI, body mass index; FIO2, fraction of inspired oxygen; PCO2, partial pressure of carbon dioxide; PEEP, positive end-expiratory pressure; PO2, partial pressure of oxygen. Note: Mean standard deviation.
rates between the two patient groups transplanted before and after LAS implementation (data not shown).
Discussion The LAS-based allocation of donor lungs has been established in the United States based on a United Network for Organ Sharing (UNOS) database and is in use since 2005. The LAS replaced an allocation system solely based on waiting time. The new system was meant to reduce wait list mortality respecting urgency and the expected maximal individual transplant benefit.3 In fact, reduction of wait list mortality has been confirmed by several studies.8–10 Such data, however, cannot be extrapolated to the situation in Germany because the LAS replaced an allocation system already based on urgency. Accumulated waiting time played only a minor role. The potential effects of the LAS implementation in Germany could only partly be predicted.11 Our novel data document for the first time the early results after lung transplantation under the new LAS-based allocation system in Germany and allow comparison to the old system. Obviously, introduction of the LAS had no relevant effect on the early results after lung transplantation. In fact, hospital stays and survival rates were comparable before and after December 10, 2011. The fact that the retrospectively calculated LASs of the patients transplanted before LAS implementation compare with those of the new era indicates comparable predicted transplant benefits of the transplanted patients before and after LAS implementation. This is also demonstrated by the fact that the majority of patients transplanted before December 10, 2011, were transplanted in “HU” status. In fact, the predicted individual transplant benefit increases with a deteriorating clinical status. It has to be noted that our current data do not allow predicting long-term outcomes after lung transplantation in Germany. Rather are they preliminary and center specific. Ongoing research with growing numbers of patients in entire Germany is required. There are data from the United States, demonstrating relatively poor results after lung transplantation in patients with high LASs when compared with patients with intermediate LASs.12,13 Together with the experience under the old allocation system in Germany, such data raise discussions on how to handle growing numbers of the critically ill patients, whose predicted individual transplant benefit is high, but whose long-term results might be unfavorable.14 For better estimates, further development of the LAS is ongoing.11 Additional patient-specific data shall be used to better predict the individual patient outcome. We have previously published that the MLTG wait list mortality is somewhat lowered after implementation of the LAS.5 In addition, recently Gottlieb et al performed a Germany-wide retrospective analysis confirming a reduction of waiting list mortality following LAS implementation.6 Analyzing our retrospective data, one has to respect certain bias by dynamic changes in the clinical routine of our center. Obviously, the MLTG transplanted the first 50 patients under the novel LAS allocation system in a shorter time frame than the last 50 under the old system. In addition, we
Kneidinger et al.
accepted donor lungs with certainly acceptable, but poorer oxygenation capacities after LAS implementation. The markedly increased utilization of the donor organ pool by the MLTG does, however, not affect the outcome after lung transplantation, at least not short term. Moreover, the MLTG recruits relatively high numbers of patients with ILDs,5 which are prioritized by the LAS, due to the relatively dynamic and rapid changes in disease progression.7 This also highlights that close multicenter follow-up on the effects of the LAS implementation on the outcome after lung transplantation are urgently needed. Competitive organ offers have been and are made outside the “T”, “U”, “HU” status and LAS.7 Eurotransplant offers donor lungs to the different transplant centers in a competitive and not patient-specific fashion. Although our data do not indicate that acceptance of competitive organ offers negatively affect short-term results after lung transplantation, the MLTG seems to more likely transplant COPD patients upon such a competitive organ offer. One reason for this might simply rely on anatomical features allowing the acceptance of also larger organ packages for COPD patients. Another reason may be that a poor clinical status in a COPD patient may not adequately be represented by the LAS.15 Our study has several limitations. Although, we provide for the first time information from a large transplant center, our ability to detect differences in outcome is limited by the small sample size and the missing long-term follow-up. Furthermore, transplant and surveillance practice did not change before and after LAS implementation in our center. However, the retrospective study comparing two consecutive cohorts might impact our results. Despite these limitations, our findings provide useful information on the impact of the LAS on survival in patients undergoing lung transplantation in Germany. Taken together, our novel preliminary data indicate that implementation of the LAS for allocation of donor lungs in Germany had no negative effect on the short-term outcome after lung transplantation. Patients transplanted before LAS implementation exhibited comparable individually predicted transplant benefits. However, future multicenter studies and long-term observations are required. Further improvements are expected from ongoing adaptations of the LAS model for better representation of patients’ status and disease entities.
Conflict of Interest There are no competing interests.
Funding No funding.
References 1 Yusen RD, Christie JD, Edwards LB, et al; International Society for
Heart and Lung Transplantation. The registry of the International Society for Heart and Lung Transplantation: thirtieth adult lung and heart-lung transplant report—2013; focus theme: age. J Heart Lung Transplant 2013;32(10):965–978 Thoracic and Cardiovascular Surgeon
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Outcome after Lung Transplantation in the Lung Allocation Score Era
Outcome after Lung Transplantation in the Lung Allocation Score Era 2 Eurotransplant: donation, waiting lists, and transplants.
3
4 5
6 7
8
10 McCue JD, Mooney J, Quail J, Arrington A, Herrington C, Dahlberg
11
12
13
14
15
PS. Ninety-day mortality and major complications are not affected by use of lung allocation score. J Heart Lung Transplant 2008; 27(2):192–196 Smits JM, Nossent GD, de Vries E, et al. Evaluation of the lung allocation score in highly urgent and urgent lung transplant candidates in Eurotransplant. J Heart Lung Transplant 2011; 30(1):22–28 Russo MJ, Worku B, Iribarne A, et al. Does lung allocation score maximize survival benefit from lung transplantation? J Thorac Cardiovasc Surg 2011;141(5): 1270–1277 Liu V, Zamora MR, Dhillon GS, Weill D. Increasing lung allocation scores predict worsened survival among lung transplant recipients. Am J Transplant 2010;10(4):915–920 George TJ, Beaty CA, Kilic A, Shah PD, Merlo CA, Shah AS. Outcomes and temporal trends among high-risk patients after lung transplantation in the United States. J Heart Lung Transplant 2012; 31(11):1182–1191 Nunley DR, Bauldoff GS, Holloman CH, Pope-Harman A. The lung allocation score and survival in lung transplant candidates with chronic obstructive pulmonary disease. Lung 2009;187(6): 383–387
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9
In: Oosterlee A, Rahmel A, eds. Annual report 2008 of Eurotransplant International Foundation. Leiden. The Netherlands: Eurotransplant International Foundation; 2008 Egan TM, Murray S, Bustami RT, et al. Development of the new lung allocation system in the United States. Am J Transplant 2006;6(5 Pt 2): 1212–1227 Valapour M, Paulson K, Smith JM, et al. OPTN/SRTR 2011 Annual Data Report: lung. Am J Transplant 2013;13(Suppl 1):149–177 Kneidinger N, Winter H, Sisic A, et al. The Munich Lung Transplant Group: The Waiting List during the first 9 month of the lung allocation score era. Thorac Cardiovasc Surg 2013;62:422–426 Gottlieb J, Greer M, Sommerwerck U, et al. Introduction of the lung allocation score in Germany. Am J Transplant 2014;14(6):1318–1327 Bekanntgaben der Herausgeber: Bundesärztekammer. Richtlinien zur Organtransplantation gem. § 16 Abs. 1 S. 1 Nrn. 2 u. 5 TPG. Dtsch Arztebl 2011;108:A-2425 / B-2037/C-2009 Gries CJ, Mulligan MS, Edelman JD, Raghu G, Curtis JR, Goss CH. Lung allocation score for lung transplantation: impact on disease severity and survival. Chest 2007;132(6):1954–1961 Kozower BD, Meyers BF, Smith MA, et al. The impact of the lung allocation score on short-term transplantation outcomes: a multicenter study. J Thorac Cardiovasc Surg 2008;135(1):166–171
Kneidinger et al.
Thoracic and Cardiovascular Surgeon
Evaluation of Short-Term Outcome after Lung Transplantation in the Lung Allocation Score Era Nikolaus Kneidinger1 Julia Holzborn2 Stephan Czerner3 Hauke Winter4 Claus Neurohr1 René Schramm2 1 Department of Internal Medicine V, Comprehensive Pneumology
Center, Member of the German Center for Lung Research, University of Munich, Munich, Germany 2 Department of Cardiac Surgery, University of Munich, Munich, Germany 3 Department of Anesthesiology, University of Munich, Munich, Germany 4 Department of Thoracic Surgery, University of Munich, Munich, Germany
Thomas Weig3
Jürgen Behr1
Address for correspondence René Schramm, MD, PhD, Department of Cardiac Surgery, University of Munich, Marchioninistrasse 15, Munich 81377, Germany (e-mail: [email protected]).
Abstract
Keywords
► ► ► ►
lung allocation score LAS lung transplantation transplant benefit
Background In December 2011, the Eurotransplant Foundation (Leiden, The Netherlands) changed the allocation system for donor lungs from a model based on urgency and waiting time to the lung allocation score (LAS). Objective The aim of the study was to investigate the effects of the LAS implementation on the early outcome after lung transplantation in Germany. Methods We therefore retrospectively studied the outcome of the last 50 patients transplanted before and the first 50 patients transplanted after LAS implementation. Results Both patient groups were comparable in baseline characteristics at the time of transplantation. Postoperative hospital stays were comparable between the groups, that is, 40.3 26.8 and 40.3 31.3 days (p ¼ 0.992). Also, survival rates on intensive care, during entire hospital stay, at 90 days, 6 month, and 1 year after transplant were comparable between the groups. The retrospectively calculated LASs of the patients transplanted under the old allocation system were not statistically significantly different from those after LAS implementation, that is, 46.5 14.2 and 51.2 17.4 (p ¼ 0.139). Conclusion We demonstrate, for the first time, that implementation of the LAS in Germany had no negative effect on the early outcome after lung transplantation. Our data indicate that patients transplanted before implementation of the LAS had a similar prospective transplant benefit.
Introduction Lung transplantation is a well-established procedure in the treatment of end-stage lung disease. Careful patient selection, modern operative techniques, and immunosuppression, as well as dedicated postoperative surveillance in experienced transplant centers provide 5-year survival rates of approximately 60%.1 The threatening shortage of donor organs
received April 18, 2014 accepted after revision July 3, 2014
requires implementation of waiting lists and establishment of allocation models. Until December 2011, donor lungs were allocated in Germany upon matching size and blood group to the patient with the highest urgency status and waiting time.2 This allocation model however neglected the prospective transplantation benefit, which is demanded by the German legislation for organ transplantation. Therefore, the Eurotransplant
© Georg Thieme Verlag KG Stuttgart · New York
DOI http://dx.doi.org/ 10.1055/s-0034-1387821. ISSN 0171-6425.
Downloaded by: Boston University. Copyrighted material.
Thorac Cardiovasc Surg
Foundation (Leiden, The Netherlands) adopted the lung allocation score (LAS) for the allocation of donor lungs in Germany on December 10, 2011. Provided matching size and blood group, the LAS allocates an organ package to the patient with the highest estimated medical urgency before transplantation and the probability of success after transplantation, to give priority to candidates who are most urgently in need of a transplant and who are expected to receive the greatest benefit.3 In the United States, the LAS was implemented in 2005, until then donor lungs had been allocated upon waiting times only. The implementation of the LAS led to a reduction of waiting list mortality in the United States.4 A similar trend could be observed in a single center study of the waiting list behavior after implementation of the LAS in our center and was recently confirmed by a Germany-wide analysis.5,6 Whether or not the implementation of the LAS has an effect on the outcome after lung transplantation in Germany remains unknown so far.
Materials and Methods Study Design This study was conducted at the Munich Transplant Center, Ludwig-Maximilians-University, Munich, Germany. In a retrospective data analysis, the early results after lung transplantation of the last 50 patients transplanted before and the first 50 patients transplanted after implementation of the LAS were compared. The Munich Lung Transplant Group (MLTG) is an institutional interdisciplinary conference consisting of designated pneumologists, cardiac and thoracic surgeons, anesthesiologists, and intensive care medicine specialists of the LudwigMaximilians-University, Munich, as well as dedicated representatives of associated and cooperating teaching hospitals and clinics. MLTG conference meetings have been held before and after implementation of the LAS every 2 weeks. It is the indented goal of the MLTG conference to regularly evaluate end-stage lung disease patients, who eventually require transplantation, and to follow up on already transplanted patients. The MLTG decides in consent of representatives of all involved disciplines to list an individual patient for lung transplantation upon the current Eurotransplant guidelines.2
Allocation Models All transplanted MLTG patients received donor lungs allocated by the Eurotransplant foundation. Until December 10, donor lungs were allocated within three distinct urgency levels, that is, transplantable (“T”), urgent (“U”), and high urgent (“HU”). Provided matching size and blood group, the organ package was allocated to the patient with the highest urgency status and waiting time. The MLTG requested “U” or “HU” status at Eurotransplant on an individual basis, which was reviewed by three external experts in an anonymous fashion. Criteria for the “U” and “HU” status had been defined by the Eurotransplant members.2 Patients with “U” and “HU” status had to be reevaluated every 4 and 2 weeks, respectively, and required intensive care unit (ICU) treatment was mandatory. Thoracic and Cardiovascular Surgeon
Kneidinger et al.
On December 10, 2011, Eurotransplant replaced the allocation system for lungs in Germany by the LAS. Since then, donor lungs were allocated to the waiting patient with the highest LAS. LASs were generated with the Web-based calculator by Eurotransplant (www.eurotransplant.org). Detailed description of how the LAS is calculated has been previously published.7 The listing status of patients with a LAS 50 (high LAS) and a LAS < 50 (low LAS) have to be updated every 14 and 90 days, respectively. The collected data need to be not older than 1 month and 7 days in low and high LAS patients, respectively. In individual cases, a transplant center may request an exceptional LAS (eLAS), when the regularly calculated LAS is thought to not adequately mirror the clinical status of the individual patient.7 An eLAS request is anonymously reviewed by an expert board and conditional value higher than calculated may be granted. Children below the age of 12 years are listed with LAS of 100 automatically. To better compare the clinical status of the two patient groups, we retrospectively calculated the LAS for those patients transplanted before implementation of the LAS on December 10, 2011. These calculations were based on the individual “U” and “HU” request data. For patients transplanted in the “T” status, we used the last data before transplant. Missing data and data older than 4 weeks before transplant were replaced by physiological values according to Eurotransplant. During the entire observation period, lungs were also transplanted after rescue allocation as competitive organ offers, irrespective of the urgency status or LAS.2 Organs may be offered by Eurotransplant in a competitive fashion to participating lung transplant centers in case of an impending loss of the organ package to maximize organ placement if a donor lung has been declined on at least three occasions or if organ loss is expected due to unstable donor conditions. The individual transplant center may then transplant the best matching patient on the waiting list.
Parameters The demographic patient data at the time of transplantation were collected from the patient files and included age, gender, body mass index, transplantation mode [single lung transplantation (SLTx) or double lung transplantation (DLTx)], and the underlying indicative lung disease. Underlying diseases were summarized in interstitial lung disease (ILD; idiopathic pulmonary fibrosis, nonspecific interstitial pneumonia, cryptogenic pneumonia, hypersensitivity pneumonitis, fibrosis secondary to connective tissue disease); chronic obstructive pulmonary disease (COPD; emphysema, α-1-antitrypsin deficiency); cystic fibrosis (CF); retransplantation; and others (pulmonary hypertension, bronchiectases, sarcoidosis, lymphangioleiomyomatosis). Donor-specific data were recruited from the donation reports provided by Eurotransplant. Postoperative end points were durations of ICU and total hospital stays, as well as ICU, hospital, 90-day, 6-month, and 1-year survival. All 100 transplanted patients were retrospectively followed up for 1 year.
Downloaded by: Boston University. Copyrighted material.
Outcome after Lung Transplantation in the Lung Allocation Score Era
Statistics Data are given as mean values standard deviation and n represents the number of patients per group. The SPSS Statistics 20.0 (Armonk, New York, United States) software package was used to calculate differences between groups utilizing the Mann–Whitney U test for continuous variables and Chi-square test for categorical variables. A value of probability of less than 0.05 was defined to indicate statistical significance. ICU and hospital stays were censored for nonsurvivors.
Results The 100 patients were transplanted by the MLTG between January 29, 2011, and July 17, 2012. The first consecutive 50 patients were transplanted within 310 days and the second consecutive 50 patients within 216 days. Both patient groups, that is, patients transplanted before and after LAS implementation, were comparable in demographic data and frequencies of transplantation mode (SLTx and DLTx) and underlying diagnoses (►Table 1). Analyses of the donor data revealed that more lungs explanted from male donors were transplanted after LAS implementation (►Table 2). In addition, the mean PO2 at 100% oxygen ventilation was significantly lower in lungs transplanted after LAS implementation (►Table 2). Before LAS implementation, the MLTG transplanted 7 patients in “T”, 5 patients in “U”, and 38 patients in “HU”
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status. The retrospectively calculated mean LAS was 46.5 14.2 (AU) in the 50 patients transplanted just before December 10, 2011. Of these, 40 patients (80%) had a retrospective LAS < 50, while 10 patients (20%) had a high LAS 50. Of the 50 patients transplanted under the LAS-based allocation system, 34 patients (68%) had a LAS < 50, while 16 patients (32%) had a LAS 50. Out of the latter, one child below the age of 12 years was listed with a LAS ¼ 100. One patient was granted an eLAS of 48. The mean LAS after December 10, 2011, was 51.2 17.4 (AU). Statistical comparison showed no significant difference between mean LASs before and after LAS implementation (p ¼ 0.139). Transplanted patients were listed 410 485 days before and 257 469 days after LAS implementation (p ¼ 0.112). Short-term survival after lung transplantation was comparable before and after LAS implementation (►Table 3). Hospital, 90-day, 6-month, and 1-year survival were not significantly different between the two patient groups (►Table 3). There was also no statistically significant difference in the 1-year survival rates before and after LAS implementation comparing distinct disease entities, that is, ILD, COPD, and CF (►Table 3). Differentiated analyses of the 1-year survival rates after retransplantation and due to other diagnosis were omitted due to the small number of patients and heterogenic diagnoses.
Table 1 Baseline characteristics of patients before and after implementation of the lung allocation scores p value
Pre-LAS (n ¼ 50)
Post-LAS (n ¼ 50)
Age (y)
49.9 13.4
46.1 14.2
0.175
Gender; female, n (%)
22 (44)
25 (50)
0.552
BMI (kg/m2)
22.5 4.5
21.2 3.6
0.108
A
26 (52)
18 (36)
0.106
B
16 (32)
16 (32)
0.999
AB
1 (2)
5 (10)
0.091
O
7 (14)
11 (22)
0.300
35 (70)
38 (76)
0.503
22 (44)
16 (32)
0.218
COPD/emphysema
8 (16)
15 (30)
0.095
Cystic fibrosis
8 (16)
9 (18)
0.792
Others
8 (16)
9 (18)
0.792
Retransplantation
Blood group, n (%)
DLTx, n (%) Diagnosis, n (%) Interstitial lung disease
4 (8)
1 (2)
0.169
Invasive ventilation before transplantation, n (%)
2 (4)
4 (8)
0.837
ECMO/ILA before transplantation, n (%)
2/0 (4)
2/2 (8)
0.837
Children < 12 y, n (%)
0 (0)
1 (2)
–
Abbreviations: BMI, body mass index; COPD, chronic obstructive pulmonary disease; DLTx, double lung transplantation; ECMO, extracorporeal membrane oxygenation; ILA, interventional lung assist. Note: Mean standard deviation. Thoracic and Cardiovascular Surgeon
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Outcome after Lung Transplantation in the Lung Allocation Score Era
Outcome after Lung Transplantation in the Lung Allocation Score Era
Kneidinger et al.
Table 2 Donor characteristics before and after implementation of the lung allocation scores Pre-LAS (n ¼ 50)
Post-LAS (n ¼ 50)
p value
Age (y)
46.9 14.6
44.8 13.7
0.450
Gender; female, n (%)
27 (54)
14 (28)
0.007
BMI
24.4 3.7
25.1 3.4
0.108
Mechanical ventilation (h)
84.5 87.9
76.7 76.4
0.639
Blood gas analysis (FIO2 100%) PO2 (mmHg)
481 61
452 75
0.041
PCO2 (mmHg)
39.5 8.2
40.1 12.5
0.777
PEEP (mbar)
6.4 1.8
6.5 1.9
0.808
The durations of ICU and total hospital stays were statistically not significantly different comparing transplanted patients before and after LAS implementation (►Table 3). In line with this, there were no relevant differences between the groups when comparing ICU and hospital stays before and after LAS implementation in a disease-specific fashion (►Table 3). The frequency of acceptance of competitive organ offers was 8 (16%) before and 9 (18%) after LAS implementation
(p ¼ 0.793). Out of these, three patients were transplanted for ILD, two patients were transplanted for COPD, and three patients were transplanted for CF before December 10, 2011. Under the new LAS system, eight competitive organ offers were accepted for COPD patients and one for others. Because competitive organ offers are allocated outside the “T”, “U”, “HU”, status and LAS, separate calculations excluding these patients were performed. However, there were no significant differences in ICU and hospital stays or survival
Table 3 Posttransplant outcome before and after implementation of the lung allocation scores Pre-LAS (n ¼ 50)
Post-LAS (n ¼ 50)
p value
19.8 24.4
21.7 29.5
0.734
Length of stay Intensive care unit (d SD) ILD
25.5 34.1
26.4 27.1
0.928
COPD
9.0 8.8
12.0 14.6
0.602
CF
16.5 11.1
13.2 14.1
0.606
40.3 26.8
40.3 31.3
0.992
Hospital (d SD) ILD
45.9 37.1
44.9 32.8
0.930
COPD
32.8 10.1
35.2 25.1
0.796
CF
41.0 19.2
28.6 11.6
0.123
Intensive care unit
90 (45)
94 (47)
0.464
Hospital
90 (45)
92 (46)
0.729
90 d
94 (47)
94 (47)
0.999
6 mo
86 (43)
88 (44)
0.768
1y
78 (39)
86 (43)
0.300
64 (14)
75 (12)
0.473
Survival, % (n)
ILD, % (n) COPD, % (n)
100 (8)
100 (15)
> 0.999
CF, % (n)
88 (7)
100 (9)
0.329
Abbreviations: CF, cystic fibrosis; COPD, chronic obstructive pulmonary disease; ILD, interstitial lung disease. Note: Mean standard deviation. Thoracic and Cardiovascular Surgeon
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Abbreviations: BMI, body mass index; FIO2, fraction of inspired oxygen; PCO2, partial pressure of carbon dioxide; PEEP, positive end-expiratory pressure; PO2, partial pressure of oxygen. Note: Mean standard deviation.
rates between the two patient groups transplanted before and after LAS implementation (data not shown).
Discussion The LAS-based allocation of donor lungs has been established in the United States based on a United Network for Organ Sharing (UNOS) database and is in use since 2005. The LAS replaced an allocation system solely based on waiting time. The new system was meant to reduce wait list mortality respecting urgency and the expected maximal individual transplant benefit.3 In fact, reduction of wait list mortality has been confirmed by several studies.8–10 Such data, however, cannot be extrapolated to the situation in Germany because the LAS replaced an allocation system already based on urgency. Accumulated waiting time played only a minor role. The potential effects of the LAS implementation in Germany could only partly be predicted.11 Our novel data document for the first time the early results after lung transplantation under the new LAS-based allocation system in Germany and allow comparison to the old system. Obviously, introduction of the LAS had no relevant effect on the early results after lung transplantation. In fact, hospital stays and survival rates were comparable before and after December 10, 2011. The fact that the retrospectively calculated LASs of the patients transplanted before LAS implementation compare with those of the new era indicates comparable predicted transplant benefits of the transplanted patients before and after LAS implementation. This is also demonstrated by the fact that the majority of patients transplanted before December 10, 2011, were transplanted in “HU” status. In fact, the predicted individual transplant benefit increases with a deteriorating clinical status. It has to be noted that our current data do not allow predicting long-term outcomes after lung transplantation in Germany. Rather are they preliminary and center specific. Ongoing research with growing numbers of patients in entire Germany is required. There are data from the United States, demonstrating relatively poor results after lung transplantation in patients with high LASs when compared with patients with intermediate LASs.12,13 Together with the experience under the old allocation system in Germany, such data raise discussions on how to handle growing numbers of the critically ill patients, whose predicted individual transplant benefit is high, but whose long-term results might be unfavorable.14 For better estimates, further development of the LAS is ongoing.11 Additional patient-specific data shall be used to better predict the individual patient outcome. We have previously published that the MLTG wait list mortality is somewhat lowered after implementation of the LAS.5 In addition, recently Gottlieb et al performed a Germany-wide retrospective analysis confirming a reduction of waiting list mortality following LAS implementation.6 Analyzing our retrospective data, one has to respect certain bias by dynamic changes in the clinical routine of our center. Obviously, the MLTG transplanted the first 50 patients under the novel LAS allocation system in a shorter time frame than the last 50 under the old system. In addition, we
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accepted donor lungs with certainly acceptable, but poorer oxygenation capacities after LAS implementation. The markedly increased utilization of the donor organ pool by the MLTG does, however, not affect the outcome after lung transplantation, at least not short term. Moreover, the MLTG recruits relatively high numbers of patients with ILDs,5 which are prioritized by the LAS, due to the relatively dynamic and rapid changes in disease progression.7 This also highlights that close multicenter follow-up on the effects of the LAS implementation on the outcome after lung transplantation are urgently needed. Competitive organ offers have been and are made outside the “T”, “U”, “HU” status and LAS.7 Eurotransplant offers donor lungs to the different transplant centers in a competitive and not patient-specific fashion. Although our data do not indicate that acceptance of competitive organ offers negatively affect short-term results after lung transplantation, the MLTG seems to more likely transplant COPD patients upon such a competitive organ offer. One reason for this might simply rely on anatomical features allowing the acceptance of also larger organ packages for COPD patients. Another reason may be that a poor clinical status in a COPD patient may not adequately be represented by the LAS.15 Our study has several limitations. Although, we provide for the first time information from a large transplant center, our ability to detect differences in outcome is limited by the small sample size and the missing long-term follow-up. Furthermore, transplant and surveillance practice did not change before and after LAS implementation in our center. However, the retrospective study comparing two consecutive cohorts might impact our results. Despite these limitations, our findings provide useful information on the impact of the LAS on survival in patients undergoing lung transplantation in Germany. Taken together, our novel preliminary data indicate that implementation of the LAS for allocation of donor lungs in Germany had no negative effect on the short-term outcome after lung transplantation. Patients transplanted before LAS implementation exhibited comparable individually predicted transplant benefits. However, future multicenter studies and long-term observations are required. Further improvements are expected from ongoing adaptations of the LAS model for better representation of patients’ status and disease entities.
Conflict of Interest There are no competing interests.
Funding No funding.
References 1 Yusen RD, Christie JD, Edwards LB, et al; International Society for
Heart and Lung Transplantation. The registry of the International Society for Heart and Lung Transplantation: thirtieth adult lung and heart-lung transplant report—2013; focus theme: age. J Heart Lung Transplant 2013;32(10):965–978 Thoracic and Cardiovascular Surgeon
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Outcome after Lung Transplantation in the Lung Allocation Score Era
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PS. Ninety-day mortality and major complications are not affected by use of lung allocation score. J Heart Lung Transplant 2008; 27(2):192–196 Smits JM, Nossent GD, de Vries E, et al. Evaluation of the lung allocation score in highly urgent and urgent lung transplant candidates in Eurotransplant. J Heart Lung Transplant 2011; 30(1):22–28 Russo MJ, Worku B, Iribarne A, et al. Does lung allocation score maximize survival benefit from lung transplantation? J Thorac Cardiovasc Surg 2011;141(5): 1270–1277 Liu V, Zamora MR, Dhillon GS, Weill D. Increasing lung allocation scores predict worsened survival among lung transplant recipients. Am J Transplant 2010;10(4):915–920 George TJ, Beaty CA, Kilic A, Shah PD, Merlo CA, Shah AS. Outcomes and temporal trends among high-risk patients after lung transplantation in the United States. J Heart Lung Transplant 2012; 31(11):1182–1191 Nunley DR, Bauldoff GS, Holloman CH, Pope-Harman A. The lung allocation score and survival in lung transplant candidates with chronic obstructive pulmonary disease. Lung 2009;187(6): 383–387
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In: Oosterlee A, Rahmel A, eds. Annual report 2008 of Eurotransplant International Foundation. Leiden. The Netherlands: Eurotransplant International Foundation; 2008 Egan TM, Murray S, Bustami RT, et al. Development of the new lung allocation system in the United States. Am J Transplant 2006;6(5 Pt 2): 1212–1227 Valapour M, Paulson K, Smith JM, et al. OPTN/SRTR 2011 Annual Data Report: lung. Am J Transplant 2013;13(Suppl 1):149–177 Kneidinger N, Winter H, Sisic A, et al. The Munich Lung Transplant Group: The Waiting List during the first 9 month of the lung allocation score era. Thorac Cardiovasc Surg 2013;62:422–426 Gottlieb J, Greer M, Sommerwerck U, et al. Introduction of the lung allocation score in Germany. Am J Transplant 2014;14(6):1318–1327 Bekanntgaben der Herausgeber: Bundesärztekammer. Richtlinien zur Organtransplantation gem. § 16 Abs. 1 S. 1 Nrn. 2 u. 5 TPG. Dtsch Arztebl 2011;108:A-2425 / B-2037/C-2009 Gries CJ, Mulligan MS, Edelman JD, Raghu G, Curtis JR, Goss CH. Lung allocation score for lung transplantation: impact on disease severity and survival. Chest 2007;132(6):1954–1961 Kozower BD, Meyers BF, Smith MA, et al. The impact of the lung allocation score on short-term transplantation outcomes: a multicenter study. J Thorac Cardiovasc Surg 2008;135(1):166–171
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