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The Fourth Joint American Transplant Meeting
Immunosuppressive Drugs After Lung Transplant
Martha Kerr
June 9, 2003 (Washington) Depletion of T cells using intravenous thymoglobulin prior to lung transplantation has allowed patients to take tacrolimus; -- in some cases, on a less-than-daily basis; -- and low-dose prednisone posttransplant without an increase in organ rejection rates.
Kenneth R. McCurry, MD, director of the lung and heart-lung transplant unit of the University of Pittsburgh in Pennsylvania, presented results of a tolerogenic protocol in 20 lung transplant patients to attendees of the American Transplant Congress, the joint annual meeting of the American Society of Transplantation and the American Society of Transplant Surgeons.
Investigators compared outcomes of the 20 patients receiving the tolerogenic protocol after lung transplantation since June 2002 with a similar group of 15 lung transplant recipients transplanted prior to the tolerogenic protocol, which is being developed by Thomas E. Starzl, MD, from the University of Pittsburgh.
Eighteen of the 20 patients are still alive and without signs of acute rejection. One died of multisystem organ failure complicated by Aspergillus infection. Cause of death in the other patient is still under investigation.
All of the remaining 18 patients are receiving prednisone 5 mg daily, while eight receive tacrolimus twice daily, five receive tacrolimus once daily, and five receive tacrolimus four times a week. Periodic adjustments in prednisone and other immunosuppressants have been required, Dr. McCurry reported, but overall, the tolerogenic protocol is proving effective. Furthermore, there have been no cases of viral infections such as Epstein-Barr virus infection or cytomegalovirus infection.
Follow-up ranges from six to 10 months. Allograft function is good in all of the survivors.
"We believe that having our patients on fewer and lower doses of tacrolimus and minimal prednisone has already offered them tremendous advantages," Dr. McCurry said in a university press release. "Down the road, we should expect that they will be at much less risk for developing the types of complications associated with high levels of immunosuppression, such as kidney dysfunction, which is quite common in lung recipients.
"Even reducing steroids in these patients is a somewhat remarkable feat, since so-called steroid-sparing has only been successful in kidney and liver recipients," Dr. McCurry said.
The tolerogenic protocol is being adopted by transplant surgeons using other organs and at other institutions. Investigators with the Immune Tolerance Network are using it as part of the Edmonton Protocol in islet transplantation and surgeons performing small bowel and multivisceral organ transplants are using it at the University of Miami.
Andreas Tzakis, MD, from the University of Miami in Florida, told Medscape that "it is ironic" that his team is using a similar protocol with small bowel transplants. "It is the most highly immunogenic organ. We were having so many problems [with rejection] that we were forced to use this approach with small bowel transplantation."
ATC 2003: Abstract 3, presented June 1, 2003; abstract 401, 601, 699, presented June 2, 2003.
Reviewed by Gary D. Vogin, MD
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