Lung Transplant Patients Successfully Tapered to Monotherapy Using Alemtuzumab  -Medscape Medical News 2004 Early results of an ongoing protocol show that both the number of immunosuppressive agents taken and the dose of each can be reduced in lung transplant patients, and with very little acute rejection, researchers said here Sunday.The study was presented by Kenneth R. McCurry, MD, from the University of Pittsburgh Medical Center in Pennsylvania, at the 2004 annual meeting of the American Transplant Congress, the joint meeting of the American Society of Transplant Surgeons and the American Society of Transplantation.At Pittsburgh, most transplant patients are being given induction therapy with a T cell depleting agent, followed by either no steroids or low-dose steroids and immunosuppressive monotherapy, usually tacrolimus. Dr. McCurry began his study in lung transplant patients in June 2002, administering thymoglobulin as the induction agent. That protocol was followed until June 2003, when new transplant patients were instead given alemtuzumab for induction.Most lung transplant patients also continued to receive a low dose of prednisone 5 mg (compared with the conventional 20 mg).  They also were given valganciclovir prophylaxis for six months before transplantation.Dr. McCurry focused his presentation on the 42 patients who had received alemtuzumab; results for the first 38 patients who received thymoglobulin were included in the abstract and not featured as prominently. Pittsburgh will be moving mostly to alemtuzumab as an induction agent in lung transplantation, said Dr.  McCurry. The patients who received alemtuzumab ranged in age from 26 to 70 years; 17 received a single lung transplant, 22 received a double-lung transplant, and two received heart and lung transplants. With follow-up of one month to one year, 41 of the 42 transplant patients are still alive. Sixty-four  percent have had no rejection; 14% had a grade 2 rejection, and only two of those 6 patients received treatment with steroids. Nine patients had a grade 3 or higher acute rejection episode.Thirty-nine patients are receiving tacrolimus monotherapy, and of those, three have tapered to four-times-weekly dosing. Three patients have added mycophenolate mofetil to their regimen. Pulmonary function is excellent, with patients having less than a 5% decline, said Dr. McCurry. There has been one case of cytomegalovirus and one case of posttransplant lymphoproliferative disorder.Session moderator Mark Barr, MD, an associate professor of cardiothoracic surgery at the University of Southern California, Los Angeles, told attendees that while Dr. McCurry's results were impressive,  he was concerned that Pittsburgh surgeons might not be able to predict which patients are more likely to reject, and that they might not be able to properly monitor for and thus, treat  rejection. "This is a gutsy protocol," he told attendees, noting the higher rejection risk with lung transplants.Dr. McCurry replied that there is no assay available to predict who might reject, and he later told Medscape that patients are closely monitored through biopsies for signs of rejection. And, he said, patients with chronic rejection would receive rescue medications such as IVIG.Stuart Knechtle, MD, a transplant surgeon at the University of Wisconsin Medical School in Madison who conducted many of the initial studies of alemtuzumab for induction, told Medscape that it is too early to say whether Dr. McCurry's results will hold. "I'd like to see continued follow-up," he said. But he added that he was not surprised by the positive results, saying "they are quite analogous to what we've seen" with other organs.Dr. Knechtle said the research also adds to the evidence that T-cell depletion plays a key role in helping to prevent rejection, and that it also helps head off longer-term problems with infection and malignancy by allowing surgeons to taper immunosuppressive therapy.Pittsburgh plans to continue treating all lung transplant patients with alemtuzumab followed by tacrolimus monotherapy, and will continue to report their results, Dr. McCurry said.