Donor Bone Marrow Injections Into Thymus Improve Outcomes For Children Getting Heart Transplants, According To Results Of Unique Trial
WASHINGTON, June 1, 2003 One to five years after heart transplantation, children who had received injections of their donors bone marrow into their thymus during the surgery had significantly fewer late rejection episodes than children who received heart transplants without the addition of the bone marrow containing donor immune system cells, according to a study performed by researchers from the University of Pittsburgh School of Medicine and Childrens Hospital of Pittsburgh.
The children receiving the injections also required fewer anti-rejection drugs. These and other results of the human trial the only one of its kind are being presented today at the American Transplant Congress (ATC), the joint scientific meeting of the American Society of Transplant Surgeons and the American Society of Transplantation. The scientific sessions are June 1 4 at the Marriott Wardman Park Hotel in Washington, D.C.
Our main objective for this pilot study was to prove intrathymic injection during heart transplantation to be both safe and feasible. But at follow-up, our findings also suggest that this approach is of benefit to patients as well. The much lower rate of acute cellular rejection occurring later than six months after transplantation is clearly a positive outcome. While it is too soon to know, the lower incidence could make the children who received intrathymic injections less likely to develop chronic rejection down the road. That would be our ultimate goal of this and any future studies, stated Steven A. Webber, MBChB, associate professor of pediatrics at the University of Pittsburgh School of Medicine and medical director of heart and heart-lung transplantation at Childrens Hospital of Pittsburgh.
Chronic rejection, which is characterized by scarring and narrowing of the hearts vessels, is a major limitation to long-term survival for heart transplant patients. It usually develops within five years in about 10 to 15 percent of all pediatric heart transplant patients and is the leading cause of late death. According to some experts, patients who experience several bouts of acute rejection, a process that is mediated by immune system T cells, are more prone to developing chronic rejection.
The thymus is a gland located behind the breastbone accessible in children during heart transplant surgery where T cells from bone marrow are educated to distinguish cells of self from those that are foreign. It is most active during infancy and childhood; after puberty it begins to shrink in size. In some adults it becomes so small that normal thymic tissue is difficult to distinguish from other surrounding tissues.
The idea behind infusing donor bone marrow into the thymus, as opposed to other sites within the body, is to fool the recipients T cells that are being educated in the thymus into thinking that the donor bone marrow is "self" as well. Those T cells that would see the donor tissue as foreign would either die in the thymus or become weakened. Without these active cells in circulation, an immune system attack against the donor organ might be avoided.
The study consisted of 14 children who received intrathymic bone marrow during heart transplantation. Immediately following heart implantation, surgeons injected the donor bone marrow contained in a small syringe into several sites of the patients thymus. Outcomes were followed for an average of 30 months, the longest being more than five years, and compared to 23 patients in whom donor bone marrow was not available at the time of their heart transplants.
While the incidence of acute rejection episodes within the first six months after transplantation was comparable in the two groups, after six months, differences were more apparent, and at one year, the rates were significantly less in the thymus patients. Among the patients who received bone marrow, there was only one episode of acute rejection between six and 12 months as well as just one episode that occurred later than 12 months, compared to six episodes that occurred after six months and 22 that occurred beyond one year in the control patients. The thymus patients also could be maintained on fewer anti-rejection drugs. Most (60 percent) required only one drug, compared to 26 percent of the control group patients.
None of the patients who received the donor bone marrow developed graft vs. host disease, a common complication of bone marrow transplantation whereby donor immune cells attack recipient tissues. No adverse events associated with the bone marrow injections were noted.
According to Dr. Webber, plans are now underway to modify the protocol so that patients will receive induction therapy as part of the immunosuppression regimen. In addition to the standard anti-rejection drugs, patients will receive a short course of a drug that depletes recipient T cells, thus reducing the number of T cells that could be activated in the early period after transplantation.
The only other known studies involving donor tissue or bone marrow injections into the thymus during transplantation are taking place in India. These involve both children and adults undergoing living-donor kidney transplantation.
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