New Tolerogenic Protocol Helps Lung-transplant Patients Wean Off Immunosuppression
A new lung-transplant protocol that represents a major departure from the traditional triple-drug therapy approach is producing good early results, according to preliminary findings presented here June 2nd at the American Transplant Congress.
Researchers from the University of Pittsburgh Medical Center (UPMC), in Pennsylvania, developed a protocol that uses lower-than-normal doses of tacrolimus, the mainstay anti-rejection drug, and lower doses of prednisone post-transplant.
The new protocol is less intensive that the three-drug combination therapy currently used in most institutions — intravenous thymoglobulin pre-transplant, followed by tacrolimus and high-dose prednisone.
If successful in the long term, the new protocol might help prevent or reduce some of the complications that result from high levels of immunosuppression, such as kidney dysfunction and life-threatening infection, according to Kenneth McCurry, MD, who directs UPMC’s lung and heart-lung transplant program.
“We expect that the complications, such as hypertension, associated with the steroids, should be fewer as well,” Dr. McCurry said.
Few studies have attempted to reduce or eliminate anti-rejection drugs in lung-transplant patients, because of fears that they might suffer irreversible immune-system attack of a vital organ — increasing the risk of death.
To date, 18 of 20 patients treated with the new protocol at UPMC have demonstrated good allograft function and are doing well, in terms of rates of complications compared with those seen with traditional treatment, Dr. McCurry noted.
The protocol involves giving patients a single 3-5 mg dose of the T-cell depleting drug thymoglobulin pre-transplant and minimal post-operative doses of tacrolimus at a trough level target of 10-15 ng/mL, in addition to a 5 mg daily dose of prednisone, which is far lower than the traditional dose.
The concept is based on more rapid weaning of patients from immunosuppression, to reduce the risk of associated complications. All of the patients whose results were presented are at least 2 months post transplant.
Although acute rejection rates were comparable to those of patients who received the higher-dose triple-drug therapy, Dr. McCurry said he and fellow researchers are hopeful that the new protocol might help reduce the rate of chronic rejection — which is notoriously difficult to treat and occurs in about half of lung-transplant patients who survive the first few years after transplant.
Dr. McCurry acknowledged that two of the 20 patients who received the new protocol have died, one from multisystem organ failure and associated complications, and the second from yet-to-be-determined causes.
