A unique new method to treat a specific group of patients who are at greater risk of rejecting a donor lung, allowing them to live longer after transplant without rejection, has been developed by the Toronto Lung Transplant Program at Toronto General Hospital, University Health Network.
This novel approach differs from other therapies which treat those who are highly "sensitized" or reactive to foreign donor lung tissue in that it uses commonly available and well-tolerated drugs in transplant programs around the world, and is begun only when the patient is in the operating room, rather than still waiting for a transplant. This reduces unnecessary treatments, the risks of side effects and costs for those who are already ill and waiting for a transplant.
The study, which followed 340 patients after lung transplant for about five years to observe how well the new approach works, is called "Survival in Sensitized Lung Transplant Recipients With Perioperative Desensitization" and published online in the February 2015, issue 2 (vol. 15) of the American Journal of Transplantation. Since the study was a retrospective one which followed patients, no external funding was required.
"We've leveled the playing field for those people who are difficult to match with a donor and would likely not get a transplant and die. We're now giving this group the same chance as others who are an easier match. They are no longer starting from a step behind," says Dr. Kathryn Tinckam, who is a transplant kidney specialist at Toronto General Hospital (TGH) and Co-Director of the HLA Lab, which is internationally recognized for its expertise in identifying and understanding high-risk recipients and how best to match them to specific donors to achieve excellent results with a lower risk of donor organ rejection.
Clinicians identified three different groups of recipients who received a lung transplant from January 1, 2008 to December 31, 2011: those who were highly "sensitized" with antibodies to the lung donor, and at highest risk of rejection, a second group with antibodies which were not directed at, or specific to, the lung donor, and those who had no antibodies, and therefore had the lowest risk of rejection. Treatments were adapted to each of these groups.
The difference amongst these groups was the levels of antibodies or proteins in the blood which identify and attack foreign tissue, such as transplanted donor organs. Antibodies develop through exposure to foreign tissue through pregnancy, blood transfusion or a previous transplant. Patients with the highest levels of antibodies are extremely hard to match to specific donors and have the highest rate of rejection. In previous studies, their survival rate at five years has been as low as 30%, in contrast to 70-75% for those who had no antibodies and are easy to match to donors.
Data from international transplant registries shows that women who are more sensitized typically make up about 60% of the waiting list, yet receive only slightly more than 40% of the transplants, suggesting that a patient with antibodies may have less access to a transplant procedure.
"We were determined to solve this problem because those patients with high levels of antibodies would often wait on the transplant list for so long that they died. This is unacceptable," says Dr. Lianne Singer, a senior author and Medical Director of the Toronto Lung Transplant Program at TGH. "We needed to develop a treatment that is safe and effective for this specific group of patients."
After using their novel three-step method, clinicians found that there was no difference in survival rates at five years between the group which had the most antibodies and the group which had none. In fact, the clinicians found that after treatment, the group with the highest antibodies had no differences in infections, rejection or function of the donor organ in comparison to the group which had no antibodies in the first place.
The Toronto Lung Transplant Program at TGH is the first group to put together elements of different approaches in a "universally applicable" protocol that can be easily used anywhere in the world. This method targets and reduces specific antibodies in patients once transplant is underway, lessening the risk to the specific donor lung- unlike other methods which lack this specificity and target a broader range of antibodies while a patient is still on the waiting list. Using various drugs and methods to first remove the antibodies from the patient's blood, and then suppress the immune system from making them further, the method allows the donor lungs to function better once transplanted, rather than to be attacked and destroyed by a patient's antibodies.
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