By Ramsey Hachem, M.D.
Washington University School of Medicine Barnes-Jewish Hospital
Division of Pulmonary and Critical Care
April, 2008
According to the latest International Society for Heart and Lung Transplantation Registry Report, the five-year survival after lung transplantation is 50% and the ten-year survival is approximately 25%. Nonetheless, survival has improved significantly in the most recent era (2000 – 2005) compared to previous eras (1988 – 1994 and 1995 – 1999). Much of this improvement is seen early after transplantation, and this has been attributed to refined surgical techniques and post-operative management, as well as better donor and recipient selection. Unfortunately, the mortality rate beyond the first year after transplantation has not changed considerably between the three eras. Graft failure remains a leading cause of death at all time points after transplantation. In general, there are two major categories of graft failure. Early after transplantation, primary graft dysfunction is a common complication and may result in graft failure when it is severe. This form of graft dysfunction results from multiple insults including donor brain death, ventilator-induced lung injury, and ischemia-reperfusion lung injury. In contrast, chronic rejection, or bronchiolitis obliterans syndrome, is the manifestation of late graft failure. Obviously, both examples of graft failure can be life threatening and the prospect of re-transplantation offers hopes of recovery and improved survival among carefully selected patients.
Not surprisingly, re-transplantation is sometimes controversial because of the scarcity of donor lungs. In general, lungs are suitable for transplantation from only 15-20% of deceased organ donors. This donor organ shortage is the primary obstacle to a more widespread use of lung transplantation and the main reason for death on the waiting list. Unfortunately, despite the recent changes in the lung organ allocation system in the United States, the number of deaths on the waiting list remains considerable. According to data from the Scientific Registry of Transplant Recipients, there were 114 deaths per 1000 patient-years in 2005 in the US. Therefore, ethical concerns are sometimes raised when one patient has a second transplant while others wait for their first transplant and are subjected to an increased risk of dying on the waiting list. This remains a contentious topic, and the transplant community has to decide whether offering re-transplantation to carefully selected patients is justifiable.
To confound matters, outcomes after re-transplantation are typically worse than after primary transplantation. The one-year survival after re-transplantation is approximately 60% and the three-year survival is less than 50%. In contrast, the one-year survival after primary transplantation is approximately 80% and the three-year survival is 65%. The two most common indications for re-transplantation are early graft failure and chronic rejection (bronchiolitis obliterans syndrome). Patients who develop graft failure early after transplantation are typically hospitalized, critically ill, and require invasive mechanical ventilation. On the other hand, many patients with graft failure due to chronic rejection are ambulatory, living at home, and have a reasonable functional capacity. This difference in the acuity of illness between these two groups generally translates into a survival difference after re-transplantation. Those who undergo re-transplantation for chronic rejection have a better survival than those with early graft failure.
There are multiple reasons for the worse outcomes after re-transplantation compared to primary transplantation. First, the operation is technically more difficult because of adhesions that form after the first transplant, which complicate the thoracic dissection and explanting the old lungs. This increases the ischemic time (the length of time the lung grafts are not being perfused with blood), bleeding complications, and sometimes results in delayed graft function. In addition, recipients of a second transplant have a higher risk of chronic rejection than those of a primary transplant. The first transplant can sometimes prime the immune system so that it may be overactive after the second transplant. Lastly, the immunosuppressive regimen after primary transplantation is associated with multiple metabolic side-effects including diabetes, high blood pressure, chronic kidney disease, hypercholesterolemia, and may perhaps accelerate vascular and coronary artery disease. Even when manageable, these complications can jeopardize the outcomes after re-transplantation.
In summary, re-transplantation can sometimes be a contentious issue in the lung transplant community because outcomes are generally worse than after primary transplantation and because of the egalitarian perspective of the allocation of donor organs that are always in short supply. Nonetheless, re-transplantation offers a realistic hope of improved survival and quality of life for carefully selected recipients who have developed graft failure.