| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
Guest Access | Sign In via User Name/Password
|
|
|
|||||||
Guest Access | Sign In via User Name/Password |
|||||||||
Philadelphia, PA
Dr. Kotloff is Associate Professor of Medicine, and Director, Program for Advanced Lung Disease and Lung Transplantation, Pulmonary, Allergy, and Critical Care Division, University of Pennsylvania Medical Center.
Address correspondence to: Robert M. Kotloff, MD, FCCP, 838 West Gates, University of Pennsylvania Medical Center, 3400 Spruce St, Philadelphia, PA 19104; e-mail: kotloff{at}mail.med.upenn.edu
Long-term preservation of allograft function remains an elusive goal following lung transplantation. Despite current immunosuppressive strategies, bronchiolitis obliterans syndrome (BOS), a disorder characterized by irreversible airflow obstruction and presumed to be a consequence of chronic allograft rejection, develops in the majority of lung transplant recipients.1 Although its course may be interrupted by periods of relative stability, BOS is invariably a progressive disorder that ultimately robs the recipient of the functional gains that accompanied transplantation. A wide range of therapies, centering on augmentation of the magnitude of immunosuppression, have been employed, but there is no consensus on the optimal approach. At best, treatment appears to slow the rate of decline rather than to permanently arrest or reverse the process. Retransplantation represents the only definitive option, but lingering questions about optimal surgical approach, patient selection, outcomes, and ethics have tempered its widespread acceptance.
Answers to these questions are emerging from two principal sources: the Pulmonary Retransplantation Registry and published reports of single-center experiences. The Pulmonary Retransplantation Registry, spearheaded by Canadian transplant surgeon Dr. Richard Novick, had at the time of its most recent publication in 1998 accrued 230 patients from 47 centers across the United States, Canada, Europe, and Australia.2 Actuarial survival of this group following retransplantation was documented to be only 47% at 1 year, significantly below the 73% 1-year survival rate for primary transplantation.3 Factors associated with improved survival following retransplantation included retransplantation for BOS (vs causes of acute graft dysfunction such as primary graft failure, intractable airway complications, and severe acute rejection), ambulatory and ventilator-independent preoperative status, and an interval of > 2 years from the time of initial transplantation. By logistic regression analysis, a patient fulfilling these criteria had a calculated probability of 1-year survival of 69%, suggesting that with application of stringent selection criteria, survival following retransplantation can approximate that of the primary procedure. Analysis of pulmonary function revealed an ominous trend among the subgroup of patients undergoing retransplantation because of severe BOS. These patients demonstrated a more rapid decline in FEV1 and a fourfold higher incidence of BOS by 3 years, compared to the group of patients who underwent retransplantation for acute graft dysfunction.4 Future iterations of the Pulmonary Retransplantation Registry, involving more patients and a longer period of follow-up, should provide further insight into whether BOS returns in an accelerated fashion in those undergoing retransplantation for this indication.
In this issue of CHEST (see page 1832), Brugiere and colleagues from Hopital Beaujon present their experience in retransplantation of 15 patients with BOS. In light of the much larger collective experience documented by the Pulmonary Retransplantation Registry, what role is served by the observations from a single center? First, while the Pulmonary Retransplantation Registry provides a measure of the average outcomes achieved by a collective group of centers of varying experience, single-center studies often provide a glimpse of the optimal outcomes achieved by a highly accomplished center. Indeed, Brugiere and colleagues achieved an impressive 1-year survival rate of 60% among a group of high-risk patients, 40% of whom were nonambulatory prior to surgery. Second, while the Pulmonary Retransplantation Registry relies on analysis of "second-hand" data collected from a questionnaire, a study emanating from a single center has the advantage of drawing from the direct observations made by the clinicians caring for the patients. This permits a more detailed description of events and complications than can be gleaned from a questionnaire. This is illustrated by the description that Brugiere and colleagues provide about the problems posed when an original allograft was left in place following retransplantation. Of 11 patients who had a retained graft, 6 patients acquired bacterial pneumonia in this graft; in four of these instances, the infection proved fatal. The susceptibility of the old graft to infection was ostensibly related to the progressive development of bronchiectasis within the graft and resultant colonization with virulent Gram-negative organisms. In addition to pneumonia, bronchorrhea requiring daily chest physiotherapy developed in three patients as a consequence of underlying bronchiectasis. Based on these observations, the authors recommend that the retransplantation procedure of choice should be one that does not leave an old graft behind (ie, ipsilateral single-lung following initial single-lung transplantation, and bilateral lung following initial bilateral or heart-lung transplantation). Given the small number of patients in the series and the failure of the larger Pulmonary Retransplantation Registry to discern a statistically significant survival difference between patients with and without a retained graft following retransplantation,4 these recommendations must be viewed as preliminary. At the very least, the article by Brugiere and colleagues should prompt those who maintain the Pulmonary Retransplantation Registry to collect more detailed data on this issue so that more definitive conclusions can be reached in the future.
The most vexing questions about retransplantation are not addressed by either the Pulmonary Retransplantation Registry or by the study by Brugiere and colleagues. In an era marked by a scarce and static donor organ supply that meets the needs of only one fourth of listed candidates, can we justify a policy of retransplantation that affords a patient a second opportunity while depriving another of a first? If we accept retransplantation as a legitimate therapeutic option, should its use be restricted to only those patients with a profile favoring survival (ie, ambulatory patients at least 2 years beyond initial transplantation with BOS) and to only those centers judged by volume and outcomes to possess the experience to perform this technically challenging procedure? Should there be, as some have advocated, an annual cap on the number of organs allocated for the purpose of retransplantation?5 The transplant community needs to confront these questions and to establish guidelines to ensure that this procedure is not applied in an arbitrary and uncontrolled fashion. Ultimately, we must strike a balance between the competing goals of maximizing the distribution of a scarce resource to the greatest number of patients vs optimizing the outcome of the individual patient.
References
This article has been cited by other articles:
|
|
 |
|
  R. M. Kotloff, V. N. Ahya, and S. W. Crawford Pulmonary Complications of Solid Organ and Hematopoietic Stem Cell Transplantation Am. J. Respir. Crit. Care Med., July 1, 2004; 170(1): 22 - 48. [Abstract] [Full Text] [PDF]
|
|
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
