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UPMC Children's Hospital of Pittsburgh has been at the forefront of pediatric heart and lung transplant research. Its research programs allow researchers and clinicians to work side-by-side to study relevant cardiovascular- and transplant-related problems in children. The goal is not only to increase the over-all body of knowledge about heart disease and transplantation in children, but also to discover methods to enhance success of the procedures.
In his 10 years as a pediatric cardiologist and transplant physician at Children’s Hospital of Pittsburgh, Steven A. Webber, MBChB, has observed great strides in improving the long-term health and survival of his young heart transplant patients.
Now, with a $14.5 million grant from the National Institutes of Health (NIH), Dr. Webber, medical director of Children’s Heart and Heart/Lung Transplantation programs, will direct innovative clinical research to improve the outcomes of pediatric heart transplant recipients.
While five-year patient survival now approaches 90 percent at Children’s, young heart transplant patients still struggle with infections, tumors and organ rejection.
Significantly, the five-year grant from NIH’s National Heart, Lung and Blood Institute will enable Dr. Webber and his team to move their research from bench to bedside - that is, apply their findings more quickly to prolong the lives of heart transplant patients.
The NIH grant funds three unique clinical projects, including one that seeks to find ways to decrease the need for immunosuppressive drugs. These medicines, used to prevent the body’s immune system from rejecting the transplanted heart, can create serious side effects.
“Even better, we would eventually like to be able to eliminate the use of immunosuppressive drugs completely,” says Dr. Webber.
Dr. Webber is the principal investigator of the grant that establishes Children’s Hospital and the University of Pittsburgh as a Specialized Center of Clinically Oriented Research in Pediatric Heart Development and Disease.
In addition, under the direction of Bradley B. Keller, MD, who will head a Clinical Research Skills Development Core, Children’s Hospital now will recruit and train physicians interested in careers in research.
Dr. Webber’s team has been exploring novel strategies to reduce immunosuppressive drug requirements, including delivery of the donor’s bone marrow to the heart recipient’s thymus, a gland in the neck where immature T-cells are activated to fight disease and foreign tissue.
In effect, the cells from the donor’s bone marrow program the cells in the thymus so they will not attack the donated heart.
To date, 14 patients who received thymic injections have had fewer episodes of rejection over time than 23 patients who did not receive the donor’s bone marrow injected into the thymus. Moreover, those who received the bone marrow were able to tolerate a lower amount of immunosuppressive drugs for one to five years after their heart transplants.
Those 37 patients will continue in the study, and new patients will be enrolled as part of the NIH grant. About 12 to 15 heart transplants are performed each year at Children's.
Another project funded by the grant is a multi-center study to identify genetic markers to help explain why certain populations of children, including African Americans, do not tolerate heart transplants as well as other children. This study will have 750 pediatric heart transplant patients.
“Once we determine genetically who will do badly and who will do well, we can individualize the immunosuppression to suit the patient's needs,” says Dr. Webber.
The third clinical research project will try to better understand the development of tumors after transplantation. This will include developing a therapy that uses the transplant patient’s own immune system cells to treat - or prevent - tumors after the heart transplant.
Three other medical centers - Boston Children’s Hospital, Children’s Hospital of Philadelphia and Cincinnati Children’s Hospital Medical Center - also have been awarded grants, which total $68 million.
Hillman Center for Pediatric Transplantation
Transplant Program Research
Clinical Trial Comparing Everolimus and Low-Dose Tacrolimus to Tacrolimus and Mycophenalate Mofetil at 6 Months Post Heart Transplant to Prevent Long-Term Complications after Pediatric Heart Transplantation
Transplant Epstein-Barr Virus (EBV) Disease – Pathogenesis and Immunotherapy
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