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J Thorac Cardiovasc Surg 1995;110:1402-1414
© 1995 Mosby, Inc.
CARDIAC AND PULMONARY REPLACEMENT |
London, Ontario, Canada; Hannover, Germany; Clichy, France; Vienna, Austria; Pittsburgh, Pa.; Houston, Tex.; and St. Louis, Mo.
Supported by a grant from the Ontario Thoracic Society.
Address for reprints: Dr. Richard J. Novick, PO Box 5339, University Hospital, London, Ontario, Canada N6A 5A5.
Abstract
An international series of pulmonary retransplantation was updated to identify the predictors of outcome and the prevalence and recurrence rate of obliterative bronchiolitis after operation. The study cohort included 139 patients who underwent retransplantation in 34 institutions in North America and Europe between 1985 and 1994. Eighty patients underwent retransplantation because of obliterative bronchiolitis, 34 because of acute graft failure, 13 because of intractable airway complications, 8 because of acute rejection, and 4 because of other indications. Survivors were followed up for a median of 630 days, with 48 patients alive at 1 year, 30 at 2 years, and 16 at 3 years after retransplantation. Actuarial survival was 65%± 4% at 1 month, 54%± 4% at 3 months, 45%± 4% at 1 year, 38%± 5% at 2 years, and 36%± 5% at 3 years; nonetheless, of 90-day postoperative survivors, 65%± 6% were alive 3 years after retransplantation. Life-table and univariate Cox analysis revealed that more recent year of retransplantation (p = 0.009), identical match of ABO blood group (p = 0.01), absence of a donor-recipient cytomegalovirus mismatch (p = 0.04), and being ambulatory immediately before retransplantation (p = 0.04) were associated with survival. By multivariate Cox analysis, being ambulatory before retransplantation was the most significant predictor of survival (p = 0.008), followed by reoperation in Europe (p = 0.044). Complete pulmonary function tests were done yearly in every survivor of retransplantation and bronchiolitis obliterans syndrome stages were assigned. Eleven percent of patients were in stage 3 at 1 year, 20% at 2 years, and 25% at 3 years after retransplantation. Values of forced expiratory volume in 1 second decreased from 1.89± 0.13 L early after retransplantation to 1.80± 0.15 L at 1 year and 1.54± 0.16 L at 2 years (p = 0.006, year 2 versus baseline postoperative value). Most of this decrease occurred in patients who underwent retransplantation because of obliterative bronchiolitis, whereas the pulmonary function of patients who underwent retransplantation because of other conditions did not significantly change. We conclude that survival after pulmonary retransplantation is improving. Optimal results can be obtained in patients who are ambulatory before retransplantation. Compared with recent data after primary lung transplantation, bronchiolitis obliterans syndrome does not appear to recur in an accelerated manner after retransplantation. As long as early mortality as a result of infection can be minimized, pulmonary retransplantation appears to offer a reasonable option in highly selected patients. (J THORAC CARDIOVASC SURG 1995;110:1402-14
During the past decade lung transplantation has evolved into a successful therapy for patients with end-stage respiratory failure. Recently, donor and recipient selection, operative technique, and postoperative care have been refined, resulting in a significant improvement in survival. 
1 Despite these advances, the postoperative course of a significant number of patients is complicated by early graft dysfunction, 2-4 an airway healingcomplication, 5,6 or acute rejection. 7,8 Furthermore, the development of obliterative bronchiolitis (OB) remains a threat to intermediate-term survivors of lung transplantation. 9-12 On occasion, these complications may prove so intractable that graft failure will ensue and the only possibility for continued survival rests with retransplantation. Since 1988 an increasing number of pulmonary retransplants have been performed because of acute or chronic graft failure. 13-21 The practice of pulmonary retransplantation has raised controversy because of the shortage of lung grafts available for primary transplantation and the poor results in the early experience with these procedures. The pulmonary retransplant registry was established in 1991 to document, in a large number of patients, the outcome and predictors of survival after pulmonary retransplantation. 13 Recently, after additional patient accrual and with increasing follow-up of retransplant recipients, the registry data were updated to determine the predictors of outcome and recurrence rate of OB after retransplantation.
PATENTS AND METHODS
Since mid-1991 patients undergoing pulmonary retransplantation have been recruited to the pulmonary retransplant registry by means of a standardized study questionnaire. These patients have been followed up prospectively with at least yearly updates of clinical status and pulmonary function. For the purposes of this report, the status of all study patients was determined in October 1994. Patients who underwent retransplantation for any indication were included in the study cohort.
The 16 parameters listed in Tables Iand II were analyzed in each patient. The chief outcome variables included survival interval after retransplantation, cause of death, and pulmonary function test data. Study form results were incorporated into the pulmonary retransplant database with use of the FoxPro database management system (Microsoft Corporation, Redmond, Wash.) on a 486DX2/66 MHz computer. Statistical analysis was performed with the SAS statistical package, version 6.04 (SAS Institute Inc., Cary, N.C.). All data were expressed as mean plus or minus the standard error of the mean. Actuarial survival was calculated by the Kaplan-Meier method 22 and Cox proportional hazards methods 23 were used to determine which variables were associated with survival after pulmonary retransplantation. Variables exhibiting a p value less than 0.25 on univariate analysis were considered for entry into a multivariate model to determine the independent predictors of survival after retransplantation. Furthermore, the risk ratio of each variable was expressed as a comparison of survival between groups, with a value of 1.0 indicating no survival difference.
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11 Complete pulmonary function test data were obtained from every survivor of retransplantation at yearly intervals. Bronchiolitis obliterans syndrome (BOS) stages were designated according to previously published criteria, based on values of forced expiratory volume in 1 second (FEV1). 1,11 The changes in absolute FEV1 values at 1 and 2 years after retransplantation were calculated for the entire study cohort, for single versus bilateral lung retransplant recipients, and for patients who underwent retransplantation because of OB versus those who underwent retransplantation because of other indications. Paired, two-tailed t tests were used to compare changes over time within each patient group, whereas unpaired, two-tailed t tests were used to contrast results between patient groups. Furthermore, contingency table analyses were used to compare the prevalence of and freedom from stages 1, 2, and 3 BOS between patient groups at 1 and 2 years after retransplantation. A p value less than 0.05 was deemed significant. RESULTS
Thirty-four lung transplant centers participated in this study, including 19 from North America and 15 from Europe. Participating institutions and the number of patients contributed by each center are listed in the appendix. A total of 139 patients have undergone retranspl antation, including 79 female and 60 male patients with a median age of 42 years (range 6 months to 62 years). Before the first transplantation procedure, 35% had a diagnosis of emphysema, 21% primary pulmonary hypertension or Eisenmenger's syndrome, 19% restrictive lung disease, 16% cystic fibrosis, and 9% miscellaneous conditions. The indications for retransplantation included OB in 80 cases, primary graft failure in 34 cases, intractable airway complications in 13 cases, histologically confirmed severe acute rejection in 8 cases, and other indications in 4 cases. Fifty-nine patients underwent repeat single-lung transplantation, 37 on the ipsilateral side and 22 on the contralateral side. Thirty patients underwent repeat double-lung transplantation, 24 double-lung transplantation after a previous single-lung transplant, and 26 single-lung transplantation after a previous double-lung or heart-lung transplant. Patient follow-up was 100% complete, with up-to-date survival and pulmonary function test data available in every patient.
Survival
The actuarial survival of all study patients is shown in Fig. 1. Of the 139 retransplant recipients, 85 have died and 54 are still living. Actuarial survival was 65% ± 4% at 1 month, 54% ± 4% at 3 months, 45% ± 4% at 1 year, 38% ± 5% at 2 years, and 36% ± 5% at 3 years. Despite the significant patient attrition early after operation, 65% ± 6% of 90-day postoperative survivors were alive 3 years after retransplantation. The median follow-up in current survivors is 630 days (mean 706 ± 67 days, range 45 to 1781 days). Forty-eight patients have reached the first anniversary, 30 the second anniversary, 16 the third anniversary, and 4 the fourth anniversary of retransplantation.
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Tables I (recipient variables) and II (donor and operative variables). Survival was not statistically different according to the age, sex, or original diagnosis of the recipients. Similarly, survival did not differ according to the predominant indication for retransplantation (Fig. 2). Univariate Cox analysis has confirmed that survival after pulmonary retransplantation is improving (Table II). In particular, actuarial survival has been significantly higher in patients who underwent retransplantation between 1992 and 1994, as opposed to between 1985 and 1991 (Fig. 3).
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Table I, Fig. 4). Before retransplantation, half of the patients were ventilator dependent whereas half required supplemental oxygen but not mechanical ventilation. There were no significant differences in survival according to the preoperative ventilator status of the retransplant recipient (Table I). Neither the official waiting time for retransplantation nor the interval between transplant procedures had a significant impact on survival, regardless of whether these variables were analyzed continuously or after the grouping of patients into approximately equal quartiles (Table I).
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Table II). In 35% of cases, an old contralateral graft remained in situ after retransplantation, whereas in 65% of cases the old graft or grafts had been excised. As shown in Table II, survival was not significantly different according to whether an old graft remained in situ after retransplantation.
Sixty-one patients underwent retransplantation in Europe and 78 in North America. In contradistinction to our previous report on retransplantation for OB, 24 no difference in survival was found between European and North American patients on univariate analysis (Table II). However, when adjusted for ambulatory status in the multivariate analysis, reoperation in Europe remained as a predictive variable (p = 0.044, adjusted risk ratio 0.61). Six of the 19 North American centers and 3 of the 15 European centers performed five or more pulmonary retransplant procedures. There was a trend toward improved survival in patients undergoing retransplantation in centers with experience in at least five pulmonary retransplant procedures (Table II).
Impact of donor-recipient ABO blood group and cytomegalovirus serologic status on survival
Seventy-eight percent of patients undergoing retransplantation received an ABO-identical graft at reoperation, whereas 22% received a graft that was ABO compatible, but not identical. Survival was significantly better in patients who received an ABO-identical graft (Fig. 5). Neither donor nor recipient cytomegalovirus serologic status was predictive of survival after retransplantation; nonetheless, the 18 cases of cytomegalovirus mismatch (cytomegalovirus-positive donor, negative recipient) were associated with significantly decreased survival after retransplantation (Table II).
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13,14,24 infection was the predominant cause of death at all time intervals after retransplantation. In this series, 48 of the 85 deaths (56%) were caused by opportunistic infection by viral, bacterial, or fungal organisms. Twenty-two percent of deaths were caused by acute failure of the second graft early after operation, 14% by recurrent OB, 4% by an airway complication, and 4% by other causes. Interestingly, only 5 of the 80 patients who underwent retransplantation because of OB died of this complication after operation.
Predictors of survival by multivariate analysis
As shown in Tables I and II, being ambulatory immediately before retransplantation was the most significant predictor of survival on multivariate analysis, followed by reoperation in Europe. Identical match of donor-recipient ABO blood group and the absence of a cytomegalovirus mismatch, which were associated with survival on univariate analysis, did not enter the multivariate model. Whereas more recent year of retransplantation was a significant predictor of survival on multivariate analysis in patients with OB, 24 the year of reoperation did not significantly influence survival in the 59 patients who underwent retransplantation because of other indications (Fig. 6). This resulted in the failure of year of reoperation to enter the current multivariate model as a factor predictive of survival after retransplantation.
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Table III shows the BOS stages of patients at yearly intervals after retransplantation. Of note is that the prevalence of stage 3 (severe) BOS was 11% at 1 year, 20% at 2 years, and 25% at 3 years after retransplantation. There were no significant differences in the BOS stage of single versus double lung retransplant recipients. Likewise, as shown in Fig. 7, there were no statistically significant differences in the prevalence of BOS between patients who underwent retransplantation because of OB versus those who underwent reoperation because of other indications (p= 0.49 and 0.45 at 1 and 2 years, respectively). Two years after retransplantation, the prevalence of stage 3 BOS was 33% in patients who underwent reoperation because of OB versus 7% in those who underwent retransplantation because of graft failure or an airway complication (p= 0.16).
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The results of this study confirm the determinants of outcome after pulmonary retransplantation that have been noted in previous reports from the registry. 13,14,24 Increasing experience with these procedures in North America and Europe has resulted in improved survival after pulmonary retransplantation, consonant with the experience in renal 25,26 and hepatic 27-29 retransplantation. Familiarity of individual centers with pulmonary retransplantation has played a role, inasmuch as the nine institutions that reported five or more retransplant procedures exhibited a trend toward improved patient survival compared with that of less experienced centers. Whereas reoperation in Europe appeared to confer a survival advantage in our previous analysis of retransplantation for OB, 24 the influence of continent of retransplantation on survival has begun to wane. This variable was no longer statistically significant on univariate analysis and had only a marginally significant p value on multivariate analysis in this study.
Donor factors at reoperation continued to play an important role in determining intermediate- term survival after pulmonary retransplantation. The presence of a donor-recipient cytomegalovirus mismatch was associated with decreased survival on univariate analysis. The influence of donor-recipient cytomegalovirus matching on survival and on the prevalence of OB after primary lung transplantation is a subject of controversy, with some studies showing no discernible effect 1 and other reports indicating that the presence of a cytomegalovirus mismatch is a highly significant predictor of early and late death after operation. 30 Although the immunosuppressive protocols after retransplantation differed among contributing centers, most retransplant recipients in the registry were administered augmented immunosuppression perioperatively, which perhaps accounted for the increased morbidity and mortality from primary cytomegalovirus infection in the 18 patients who received a cytomegalovirus-mismatched graft.
Another important finding in this study is that an identical match of donor-recipient ABO blood group is significantly associated with survival after retransplantation. A trend in this direction was noted in the first report from the retransplant registry in 1993. 13 A similar analysis in a larger number of patients after primary lung transplantation has indicated only a trend toward improved survival (p = 0.11) in patients receiving an ABO-identical, as opposed to an ABO-compatible, graft (personal communication, Ms. Mary Pohl, St. Louis International Lung Transplant Registry). The importance of an identical match of donor-recipient ABO blood group in pulmonary retransplantation awaits confirmation by the long-term follow-up of a larger number of patients with secondary lung grafts.
The multivariate analysis indicated that the most significant predictor of survival after retransplantation was the ambulatory status of the recipient immediately before reoperation. Patients who were able to walk more than 50 m before retransplantation were more than twice as likely to be alive at all time intervals after operation (adjusted risk ratio of death 0.46, p = 0.008). In 1994, almost half of the newly registered patients were ambulatory before retransplantation, as opposed to 26% in previous years. Similarly, very few patients underwent retransplantation in 1993 and 1994 in the setting of severe multiorgan failure, which has been shown to predict a greater than 90% perioperative mortality rate not only in pulmonary retransplantation 13,24 but also in hepaticretransplantation. 29 These data indicate that patient selection for pulmonary retransplantation may be improving, as additional experience with these procedures is gained in North America and Europe.
Given the absolute necessity to make optimal use of scarce donor lung grafts, it is important to determine whether OB or BOS develops in an accelerated manner after retransplantation. We are aware of only three papers in which the prevalence of BOS after primary lung or heart-lung transplantation has been reported in an actuarial manner. A recent study from Stanford indicated that the actuarial freedom from "clinical OB" was 71% at 1 year and approximately 55% to 60% at 2 and 3 years after heart-lung transplantation. 12 In a report from the University of North Carolina, the actuarial freedom from stages 1, 2, and 3 BOS was 85% to 90% at 1 year and 60% at 2 years after bilateral lung transplantation for cystic fibrosis. 31 In a recent study from Hannover, the prevalence of BOS in more than 100 patients who underwent primary lung transplantation was contrasted with that of 14 patients who underwent retransplantation. 21 At 1 year after operation, 88% of primary lung transplant recipients and 80% of patients who underwent pulmonary retransplantation were free from stage 3 (severe) BOS. At 2 years, however, 72% of primary lung graft recipients were free from stage 3 BOS, whereas only 27% of retransplant recipients had avoided this complication. 21 The Hannover group regards the development of severe BOS as a failure of immunosuppression and has recently switched to an FK506-based protocol in its pulmonary retransplant recipients in an attempt to slow the rate of development of BOS in this patient subset. 21 Other centers have had afavorable experience with FK506 in lung transplantation, 32 although further investigations are required to determine whether modified immunosuppression is capable of reducing the risk of graft loss in the intermediate-term after operation.
The pulmonary function test analyses performed in this study have determined that the prevalence of stages 1, 2, and 3 BOS is almost identical at 1 and 2 years after retransplantation as in the previously noted series of primary lung transplantation. 12,21,31 Our 80% rate of freedom from stage 3 BOS 2 years after retransplantation compares favorably with the freedom from stage 3 BOS in recipients of primary lung grafts in the Hannover study. 21 Furthermore, our 63% rate of freedom from stages 1, 2, and 3 BOS at 2 years is similar to the 60% freedom from the same BOS stages in the North Carolina experience. 31 Current evidence, therefore, indicates that in patents who undergo pulmonary retransplantation BOS develops with a similar prevalence and intensity as in recipients of primary lung grafts. Although in some patients rapidly progressive BOS develops after retransplantation, the majority of retransplant survivors have acceptable pulmonary function in the intermediate-term after operation.
Detailed analysis of patient subgroups has confirmed that pulmonary function declines at a similar rate in single and bilateral lung retransplant recipients. Interestingly, FEV1 values decreased significantly by 2 years after operation in patients who underwent retransplantation because of OB, but not in patients who underwent retransplantation because of acute graft failure or an airway complication. Although the differences in FEV1 and the prevalence of stage 3 BOS were not statistically significant between these two patient groups at 2 years, it is possible that with further patient follow-up and additional patient accrual statistically significant differences will be realized. These results underline the importance of research on alternative immunosuppressive protocols in primary and secondary lung transplantation, so that the prevalence of BOS and its recurrence rate after retransplantation can be minimized.
In summary, survival after pulmonary retransplantation is improving because of increasing experience and better patient selection. The goal of the retransplant registry has been to accelerate this trend by determining the factors associated with survival and, ultimately, with excellent graft function after retransplantation. Current evidence indicates that optimal results may be anticipated in ambulatory candidates who receive an ABO-identical graft that is matched for cytomegalovirus status. Retransplant recipients who survive the first 3 postoperative months have a medium-term prognosis similar to that of patients with first-time lung transplants. Efforts to minimize early mortality from infection should improve further the results of retransplantation and justify the continued performance of these procedures in highly selected patients.
Appendix: APPENDIX
Contributing centers, thoracic surgeons, pulmonologists, and coordinators are as follows: Allegemeine Krankenhaus, Vienna, Austria; Walter Klepetko, Bernhard Schlechta, Abelheid End (18 patients). Medizinische Hochschule Hannover, Hannover, Germany; Hans-Joachim Schäfers (14 patients). Presbyterian University Hospital, Pittsburgh, Pa.; Bartley Griffith, Robert Hardesty, Ann Lee, Debbie Opacic (12 patients). Hopital Beaujon, Clichy, France; Bernard Andréassian, Jean-Pierre Duchatelle (10 patients). Baylor-Methodist Hospital, Houston, Tex.; Adaani Frost, George Noon, H. David Short, Janine O'Leary (10 patients). Toronto Hospital, Toronto, Ontario, Canada; Tim Winton, Janet Maurer, Massina Scavuzzo, Louise Won (9 patients). University of Minnesota Health Center, Minneapolis, Minn.; R. Morton Bolman, Marshall Hertz, Beth Dosland (6 patients). Loyola University Medical Center, Maywood, Ill.; James Houck, Edward Garrity (5 patients). St. Louis Children's Hospital, St. Louis, Mo.; Thomas Spray, George Mallory (5 patients). Washington University-Barnes Hospital, St. Louis, Mo.; Alec Patterson, Joel Cooper, Mary Pohl (4 patients). University of North Carolina Medical Center, Chapel Hill, N.C.; Tom Egan, Ellen Cairns (4 patients). Stanford University Medical Center, Stanford, Calif.; Bruce Reitz, Tom Burdon (3 patients). University of Michigan Medical Center, Ann Arbor, Mich.; Michael Deeb, Ros Florn (3 patients). University of Texas Medical Center, San Antonio, Tex.; John Calhoon, Kent Trinkle (3 patients). Montreal General Hospital, Montreal, Quebec, Canada; Hani Shennib (3 patients). Freeman Hospital, Newcastle-upon-Tyne, England; John Dark, Paul Corris (3 patients). Rikshospitalet, Oslo, Norway; Odd Geiran, Oystein Bjortuft (2 patients). University of Iowa Hospital, Iowa City, Iowa; Louis Lanza (2 patients). University of Pennsylvania Hospital, Philadelphia, Pa.; Larry Kaiser, Nancy Blumenthal, Angela Wurster (2 patients). Vanderbilt University Medical Center, Nashville, Tenn.; Jim Loyd, Bill Frist (2 patients). University of Wisconsin Medical Center, Madison, Wis.; Robert Love, Debbie Welter (2 patients). Papworth Hospital, Cambridge, England; John Wallwork (2 patients). Hopital d'Enfants de la Timone, Marseille, France; Dominique Metras (2 patients). Hopital Xavier-Arnozan, Pessac, France; Louis Couraud, Claire Dromer (2 patients). Klinikum Grosshadern, Munich, Germany; Bruno Reichart, Florio Wagner (2 patients). Centre for Health Sciences, Winnipeg, Manitoba, Canada; Wayne Kepron, Helmut Unruh (1 patient). Brigham and Women's Hospital, Boston, Mass.; Stephen Mentzer, David Sugarbaker, Carol Coakley (1 patient). University of Virginia Health Sciences Center, Charlottesville, Va.; Curtis Tribble, John Truwit, Margaret Ball (1 patient). Hopital Erasme, Brussels, Belgium; Martine Antoine, Marc Estenne (1 patient). University Hospital, Rigshospitalet; Gosta Pettersson, Ulrik Gerner Svendsen (1 patient). Helsinki University Central Hospital, Helsinki, Finland; Ari Harjula (1 patient). Centre Medico-Chirurgical Foch, Suresnes, France; Alain Bisson (1 patient). Academisch Ziekenhuis Groningen, Groningen, The Netherlands; Wim de Boer (1 patient). Universitätsspital Zürich, Zürich, Switzerland; Walter Weder (1 patient).
Appendix: DISCUSSION
Dr. C. G. A. McGregor (Rochester, Minn.).
I would like to congratulate Dr. Novick and his colleagues for successfully forming the pulmonary retransplant registry. Clearly, no individual center develops enough experience with such relatively unusual techniques to be able to draw meaningful conclusions as to optimal management. For example, perhaps only 15 of the 77 lung transplant centers in the United States perform more than 10 transplants per year.
I would encourage members of the Association to pursue similar efforts whether as registries of multicenter studies in pursuit of knowledge as to the best management of other rare clinical challenges in cardiothoracic transplantation. Examples that come to mind include cardiac transplantation for amyloid disease or cardiac tumors and pulmonary transplantation for systemic collagen diseases; there are many other examples.
Pulmonary retransplant candidates comprise a group of patients with extremely challenging conditions in that they have received recurrent heavy immunosuppressive therapy for treatment of OB or recalcitrant rejection including steroids, cytolytic therapy, and sometimes total lymphoid irradiation. These patients are, therefore, in profoundly immunosuppressed conditions and not in a good state for retransplantation in terms of the likelihood of infection and perhaps the development of posttransplant lymphoproliferative disorders. It is no surprise, therefore, that 56% of the early deaths in this series were caused by infection. Only 29% of the retransplant recipients whose results are presented in this paper were ambulatory and half were ventilator dependent. Although the survival of 45% at 1 year is disappointing, it is important to note that those patients who survived for 90 days after operation had a survival thereafter comparable with that of primary lung transplant recipients.
It is also interesting that the interval between transplantation and retransplantation and the reason for retransplantation did not have an impact on survival, unlike the situation in heart retransplantation in which early retransplantation, which is commonly necessitated by recalcitrant rejection, has a 1-year survival approximately half of that for late retransplantation, which is commonly done because of accelerated transplant atherosclerosis.
This paper informs us that the preoperative status of the patient as reflected by ambulation immediately before retransplantation is the critical factor in a successful outcome. If, with this important information, we can reduce early mortality, then we know from this presentation that the rate of recurrence of OB will be no greater than that after a primary transplant and that satisfactory lung function will be achieved.
I would like to ask Dr. Novick the following three questions. First, previous reports from the registry indicated that removal of the previously transplanted lung was important, but the current report suggests this is no longer true. Is this change simply a reflection of more numbers in the registry? Second, there seems to be a paradox in that being ambulatory is important in survival, and yet being ventilator dependent is not. Can you explain this? Third, can you comment on the contrast between the indication and time interval before retransplantation not being a factor in survival in pulmonary retransplantation compared with the situation in heart retransplantation?
Dr. Novick.
In 1993 I presented a paper on 33 patients who underwent retransplantation because of OB. The survival of patients without an old, retained contralateral graft was significantly better than that of patients with an old contralateral graft. Two years have gone by, the number of patients in the registry has increased fourfold (to 139), and patient selection and postoperative treatment have improved. Likely, increased patient accrual to the pulmonary retransplant registry and these other factors have muted the importance of the presence of an old contralateral graft as a predictor of poor outcome after retransplantation.
There was no difference in survival between the 70 patients who were receiving ventilator support and the 69 patients who were not receiving ventilator support before retransplantation. Of the 70 patients who were on a ventilator, however, 33 were ambulatory; they were able to walk at least 50 m with assistance from the nursing and physiotherapy staff. Thus, if the patients are rehabilitated in every other way except for the ventilatory status before retransplantation, and if they survive the perioperative period, in all likelihood they will do well.
Finally, concerning the interval between transplant operations, it is true that in cardiac retransplantation an interval of greater than 6 months correlates with a successful outcome. When analyzed as a continuous variable after pulmonary retransplantation, there is no relationship between the interval between transplants and survival.
Dr. Alvaro Montoya (Chicago, Ill.).
At Loyola University in Chicago we have done 135 lung transplants since 1991. Seven of these patients required retransplantation. We had four survivors. One of these survivors was a 21-year-old girl with cystic fibrosis in which OB developed. I elected to do a retransplant in her case. I retransplanted the heart and lung because of clinical feasibilities. OB developed in the new transplanted lungs 3 months after retransplantation and she died. We had been debating about doing a second retransplantation, but she died before we came to a conclusion.
We now have six patients on the waiting list for retransplantation. One of these is a 32-year-old marathon runner who received double-lung transplantation because of alveolar cell carcinoma. Now he needs a retransplant and we are debating about whether to do it.
We are committed to these patients. For their care we performed transplantation one time; maybe we should perform retransplantation if it is required. My question is simple. Should we continue to do retransplants? We do not retransplant hearts. I have asked why and the answer was, we do not have donors. Should be continue to do retransplants on patients with lung disease?
Dr. Novick.
In brief, I believe that as a minimum a pulmonary retransplant candidate should meet the same criteria as a first-time lung transplant candidate and perhaps be even more highly selected. Our findings, which show satisfactory results in the intermediate term of 90-day postoperative survivors of retransplantation, indicate that we should still be retransplanting lungs, but that patient selection should be further refined.
Acknowledgments
We thank the contributing thoracic surgeons, pulmonary medicine physicians, and recipient coordinators who have participated in the pulmonary retransplant registry. We also acknowledge the assistance of Heather Motloch in manuscript preparation and of Theresa Novick, MSc, in data collection and analysis.
Footnotes
Read at the Seventy-fifth Annual Meeting of The American Association for Thoracic Surgery, Boston, Mass., April 23-26, 1995. 
J THORAC CARDIOVASC SURG 1995;110:1402-14
References
This article has been cited by other articles:
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  S. M. Kawut, D. J. Lederer, S. Keshavjee, J. S. Wilt, T. Daly, F. D'Ovidio, J. R. Sonett, S. M. Arcasoy, and M. L. Barr Outcomes after Lung Retransplantation in the Modern Era Am. J. Respir. Crit. Care Med., January 1, 2008; 177(1): 114 - 120. [Abstract] [Full Text] [PDF]
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R. J. Novick, L. W. Stitt, K. Al-Kattan, W. Klepetko, H.-J. Schafers, J.-P. Duchatelle, A. Khaghani, R. L. Hardesty, G. A. Patterson, and M. H. Yacoub Pulmonary Retransplantation: Predictors of Graft Function and Survival in 230 Patients Ann. Thorac. Surg., January 1, 1998; 65(1): 227 - 234. [Abstract] [Full Text] [PDF]
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R. J. Novick, L. Stitt, H.-J. Schafers, B. Andreassian, J.-P. Duchatelle, W. Klepetko, R. L. Hardesty, A. Frost, and G. A. Patterson PULMONARY RETRANSPLANTATION: DOES THE INDICATION FOR OPERATION INFLUENCE POSTOPERATIVE LUNG FUNCTION? J. Thorac. Cardiovasc. Surg., December 1, 1996; 112(6): 1504 - 1514. [Abstract] [Full Text]
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Contralateral Pneumonectomy After Single-Lung Transplantation for Emphysema Ann. Thorac. Surg., April 1, 1996; 61(4): 1286 - 1287. [Full Text]
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