The Pulmonary Retransplant Registry has had several previous publications:

Novick RJ, Stitt L, Schäfers JH, Andréassian B, Duchatelle JP, Klepetko W, Hardesty RL, Frost A, Patterson GA. Pulmonary retransplantation: does the indication for surgery influence postoperative lung function? J Thorac Cardiovasc Surg 1996;112:1504-14.
Novick RJ, Schäfers HJ, Stitt L, Andréassian B, Duchatelle JP, Klepetko W, Hardesty RL, Frost A, Patterson GA. Recurrence of obliterative bronchiolitis and determinants of outcome in 139 pulmonary retransplant recipients. J Thorac Cardiovasc Surg 1995;110:1402-14.
Novick RJ, Schäfers HJ, Stitt L, Andréassian B, Klepetko W, Hardesty RL, Frost A, Patterson GA. Seventy-two pulmonary retransplantations for obliterative bronchiolitis: predictors of survival. Ann Thorac Surg 1995;60:111-6.
Novick RJ, Andréassian B, Schäfers HJ, Haverich A, Patterson GA, Kaye MP, Menkis AH, McKenzie FN. Pulmonary retransplantation for obliterative bronchiolitis: Intermediate-term results of a North American - European series. J Thorac Cardiovasc Surg 1994;107:755-63.
Novick RJ, Kaye M, Patterson G, Andréassian B, Klepetko W, Menkis AH, McKenzie FN. Redo lung transplantation: a North American - European experience. J Heart Lung Transplant 1993;12:5-16.

Reprinted with permission from the Society of Thoracic Surgeons (The Annals of Thoracic Surgery 1998, 65, 227-234)

Richard J. Novick, MD, Larry W. Stitt, MSc, Khaled Al-Kattan, MD, Walter Klepetko, MD, Hans-Joachim Schäfers, MD, Jean-Pierre Duchatelle, MD, Asghar Khaghani, MD, Robert L. Hardesty, MD, G. Alexander Patterson, MD, and Magdi H. Yacoub, MD, for the Pulmonary Retransplant Registry.

From the Departments of Surgery and Epidemiology and Biostatistics, the London Health Sciences Centre, the Robarts Research Institute, and the University of Western Ontario, London, Ontario, Canada; Harefield, England; Vienna, Austria; Hannover and Homburg, Germany; Paris, France; Pittsburgh, Pennsylvania; St. Louis, Missouri; and 47 participating centers in the Pulmonary Retransplant Registry.

Abstract

Background. Despite improving results in lung transplantation, a significant number of grafts fail early or late postoperatively. The pulmonary retransplant registry was founded in 1991 to determine the predictors of outcome after retransplantation. We hypothesized that ambulatory status of the recipient and center retransplant volume, which had been previously shown to predict survival after retransplantation, would also be associated with improved graft function postoperatively.

Methods. Two hundred thirty patients underwent retransplantation in 47 centers from 1985 to 1996. Logistic regression methods were used to determine variables associated with, and predictive of, survival and lung function after retransplantation.

Results. Kaplan-Meier survival was 47% ± 3%, 40% ± 3%, and 33% ± 4% at 1, 2, and 3 years, respectively. On multivariable analysis, the predictors of survival included ambulatory status or lack of ventilator support preoperatively (p = 0.005; odds ratio, 1.62; 95% confidence interval, 1.15 to 2.27), followed by retransplantation after 1991 (p = 0.048; odds ratio, 1.41; 95% confidence interval, 1.003 to 1.99). Ambulatory, nonventilated patients undergoing retransplantation after 1991 had a 1-year survival of 64% ± 5% versus 33% ± 4% for nonambulatory, ventilated recipients. Eighty-one percent, 70%, 62%, and 56% of survivors were free of bronchiolitis obliterans syndrome at 1, 2, 3, and 4 years after retransplantation, respectively. Factors associated with freedom from stage 3 (severe) bronchiolitis obliterans syndrome at 2 years after retransplantation included an interval between transplants greater than 2 years (p = 0.01), the lack of ventilatory support before retransplantation (p = 0.03), increasing retransplant experience within each center (fifth and higher retransplant patient, p = 0.04) and total center volume of five or more retransplant operations (p = 0.05).

Conclusions. Nonambulatory, ventilated patients should not be considered for retransplantation with the same priority as other candidates. The best intermediate-term functional results occurred in more experienced centers, in nonventilated patients, and in patients undergoing retransplantation more than 2 years after their first transplant. In view of the scarcity of lung donors, patient selection for retransplantation should remain strict and should be guided by the outcome data reviewed in this article.

Figure 1
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Figure 3
Figure 4
Figure 5
Figure 6
Figure 7

Table 1
Table 2
Table 3
Table 4

Figure 1. Actuarial survival of patients undergoing retransplantation because of obliterative bronchiolitis versus those undergoing retransplantation because of other indications (log-rank p value = 0.07)

Figure 2. Actuarial survival according to the interval between transplantation procedures (log-rank p value = 0.002)

Figure 3. Actuarial survival according to the requirement for ventilator support before retransplantation (log-rank p value = 0.002)

Figure 4. Actuarial survival according to the recipient's ambulatory staus and requirement for ventilator support preoperatively (log-rank p value = 0.003)

Figure 5. Actuarial survival according to the year of retransplantation and the recipient's requirement for ventilator support preoperatively (log-rank p value = 0.001)

Figure 6. Prevalence of stages 0, 1, 2, and 3 bronchiolitis obliterans syndrome (BOS) at 1, 2, and 5 years after retransplantation.

Figure 7. Forced expiratory volume in 1 second (FEV₁) values in 3-year survivors who underwent retransplantation because of obliterative bronchiolitis (OB) versus non-OB conditions.
p value = 0.04 at 2 years; p value = 0.01 at 3 years.
SEM = standard error of the mean.

Table I.
Factors Associated with Survival after Retransplantation on Univariable Analysis

	Unadjusted for Center Effect		Adjusted for Center Effect
Variable	Odds ratioa	p Value	Odds ratioa	p Value
Indication for retransplantation, all indications	NAb	0.150	NAb	0.115
Indication for retransplantation, OB vs non-OB	1.32 (0.95, 1.84)	0.099	1.45 (1.03, 2.06)	0.035
Ambulatory before retransplantation	1.62 (1.12, 2.33)	0.010	1.93 (1.31, 2.83)	<0.001
Ventilator support	0.61 (0.44, 0.85)	0.003	0.53 (0.37, 0.74)	<0.001
Either ambulatory or not on ventilator support	1.72 (1.23, 2.40)	0.001	2.06 (1.45, 2.94)	<0.001
Both ambulatory and not on ventilator support	1.57 (1.08, 2.28)	0.017	1.82 (1.24, 2.68)	0.002
Interval between transplants, continuous	NAb	0.006	NAb	0.003
Interval between transplants, >2 y vs < or =2 y	1.83 (1.21, 2.76)	0.004	1.96 (1.28, 2.99)	0.002
Year of reoperation, continuous	NAb	0.005	NAb	<0.001
Year of reoperation, 1992-95 vs 1985-91	1.55 (1.11, 2.15)	0.010	1.66 (1.17, 2.35)	0.005
Donor CMV negativity	1.38 (0.98, 1.93)	0.063	1.52 (1.07, 2.17)	0.021
Donor-recipient ABO blood group identity	1.49 (0.96, 2.29)	0.074	1.61 (1.03, 2.51)	0.038

^a Odds ratio >1.0 indicate increased survival, whereas ratios <1.0 indicate decreased survival after retransplantation.
^b Odds ratio not calculated because variable has more than two categories.
Odds ratio has 95% confidence limits.
CMV, cytomegalovirus; OB, obliterative bronchiolitis; NA, not applicable

Table 2.
Subset of Variables Predictive of Survival on Multivariable Analysis

	Unadjusted for Center Effect		Adjusted for Center Effect
Predictive Variable	Odds ratioa	p Value	Odds ratioa	p Value
Either ambulatory or not ventilator dependent	1.62 (1.15, 2.27)	0.005	1.93 (1.39, 2.79)	<0.001
Year of retransplantation, > or =1992 vs < or =1991	1.41 (1.00, 1.99)	0.048	1.53 (1.05, 2.21)	0.025

^a Odds ratio >1.0 indicate increased survival, whereas ratios <1.0 indicate decreased survival after retransplantation.
Odds ratio has 95% confidence limits.

Table 3.
Probability of 1-Year Survival After Pulmonary Retransplantation Under Two Hypothetical Scenarios^a

Patient Characteristic	Coefficient	Scenario 1	Scenario 2
Recipient age (years)	-0.0039337	30	50
Sex (0 if male, 1 if female)	-0.040716	Male	Female
Ambulatory before retransplant? (0 if ambulatory, 1 if not ambulatory)	-0.57020	Yes	No
Ventilator dependent before retransplantation? (0 if dependent, 1 if not dependent)	0.37313	No	Yes
Indication for retransplantation = obliterative bronchiolitis (0 if yes, 1 if no)	0.12719	Yes	No
Indication for retransplantation = acute graft failure (0 if yes, 1 if no)	-0.27725	No	Yes
Interval between transplantations (days)	0.0003452	4 years	10 days
Year of retransplantation (0 if after 1991, 1 if 1991 or before)	-0.33245	After 1991	1991 or before
Center experience with > or =5 retransplantations (0 if yes, 1 if no)	-0.42775	Yes	No
Probability of 1-year survival	---	69%	25%

^a Probability of 1-year survival can be calculated using the coefficients presented within a logistic regression model. The model also includes a constant = 0.33670.

Table 4.
Factors Associated with Freedom from BOS (Stage 0) or the Absence of Severe BOS (BOS Stages 0-2) 2 Years after Retransplantation

	BOS Stage 0		BOS Stages 0-2
Variable	Odds ratioa	p Value	Odds ratioa	p Value
Absence of ventilator support before retransplantation	1.84 (0.92, 3.70)	0.083	2.03 (1.07, 3.86)	0.031
Interval between transplants, continuous	NAb	0.047	NAb	0.051
Interval between transplants, >2 y vs < or =2 y	2.14 (1.03, 4.42)	0.041	2.45 (1.23, 4.85)	0.011
Donor CMV negativity	1.97 (0.99, 3.90)	0.054	1.52 (0.81, 2.85)	0.193
Individual center experience, >4th vs < or =4th retransplant	1.93 (0.98, 3.80)	0.057	1.90 (1.02, 3.53)	0.044
Total center retransplant volume, > or = 5 vs <5 retransplants	2.04 (0.91, 4.56)	0.082	2.04 (0.99, 4.22)	0.053

^a Odds ratios >1.0 indicate an increased probability and ratios <1.0 a decreased probability of BOS stage 0 or stages 0-2.
^b Odds ratio not calculated because variable has more than 2 categories.
Odds ratio has 95% confidence limits.
BOS, bronchiolitis obliterans syndrome; CMV, cytomegalovirus; NA, not applicable

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