The National Heart, Lung, and Blood Institute (NHLBI) of the National Institutes of Health (NIH) has awarded a team from Children's Hospital and the University of Pittsburgh a $14.5 million grant to develop novel approaches that seek to improve the outcomes of pediatric heart transplant recipients. The five-year grant establishes the University of Pittsburgh as a Specialized Center of Clinically Oriented Research (SCCOR) in Pediatric Heart Development and Disease. Such a center encourages basic science research findings to be applied more rapidly to address specific clinical problems.
National statistics show that c hildren who receive heart transplants don't do as well as adult recipients. Transplant recipients must take medication to suppress rejection of the transplanted organ, but the medications often cause other complications that affect long-term survival. The NHLBI grant funds three projects that will assess different aspects of immunosuppression in pediatric heart recipients.
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One project takes bone marrow from the donor and delivers it to the heart recipient's thymus, a gland where immature T-cells that fight disease and foreign tissue are activated. The idea is to get the thymus to program T-cells so they won't attack the donated heart. Preliminary results in 14 patients who received thymic injections indicated that those patients experienced significantly fewer episodes of rejection in the long run than 23 recipients who did not. The patients who received the bone marrow also needed less immunosuppression one to five years after the procedure. This study will be expanded under the NHLBI grant.
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A second project will investigate Epstein-Barr virus (EBV) infection and immune response, culminating with a Phase I trial of a cellular immunotherapy for the prevention and treatment of post-transplant lymphoproliferative disease (PTLD). This study considers a new way to prevent certain post-transplant tumors that are related to immunosuppression. Conventional treatment of the tumors involves reducing immune-suppression medicines, but that can result in organ rejection.
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The grant also funds a multi-center study of the genetic variability that may predict an individual's transplant outcome and help explain why African Americans do worse than other groups of patients. Such an approach would allow doctors to individualize treatments, diminishing the chances of rejection and minimizing drug-related complications.
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Four cores will support the clinical projects. Dr. Steven Webber will lead the Administrative Core. Dr. Diana Metes will lead the Immunological Monitoring Core; Sheryl F. Kelsey, Ph.D., professor of epidemiology at GSPH, will lead the Biostatistics and Data Management Core; and Bradley B. Keller, M.D., professor of pediatrics at the School of Medicine and chief of cardiology at Children's, will head the Clinical Research Skills Development Core. This unique core will provide a structured training environment for talented future physician-scientists who aspire to careers in translational research.
The center grant brings together experts in pediatric cardiology and transplant medicine, transplant surgery, immunology, pharmacology, infectious diseases, molecular genetics and biostatistics from the School of Medicine, Graduate School of Public Health, Starzl Transplantation Institute and Children's Hospital of the University of Pittsburgh Medical Center.
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