Biography
Dr. Ferrara is a Professor of Medicine and Pediatrics at the University of Michigan Medical School and the Director of the Blood and Marrow Transplant Program at the University of Michigan Comprehensive Cancer Center. He received his BA from Xavier University and an MA from Oxford University before obtaining his medical degree in 1980 from Georgetown Medical School. He was an intern and resident in Pediatrics at Children's Hospital in Boston and completed his Pediatric Hematology/Oncology training at the Dana Farber Cancer Institute before joining the faculty of Harvard Medical School where he remained until 1998. Dr. Ferrara is one of the world's leading authorities on the immunologic complications of bone marrow transplantation and his research interests focus on making transplantation safer and more available to a wider group of patients. He currently serves on the National Board of Directors of the American Society for Blood and Marrow Transplantation and has received numerous honors for his contributions to this field including the Stohlman Scholar Award from the Leukemia and Lymphoma Society and the Alexander von Humboldt Award from the German government.
Abstract
Novel Strategies to Improve Allogenic BMT
Allogeneic bone marrow transplantation (BMT) is an important curative therapy for a number of hematologic malignancies, but it is complicated by Graft-vs.-host disease (GVHD) and idiopathic pneumonia syndrome (IPS). Research in Dr. Ferrara's laboratory has demonstrated agents that protect the GI tract provide new opportunities for prevention of the cascade of inflammatory cytokines that can reduce these complications. This project will support several clinical trials designed to test novel agents that can reduce the toxic complications of BMT. Funding from the Doris Duke Charitable Foundation will facilitate the laboratory evaluation of patient samples from all of these trials, support the design of new trials of these agents and enhance the mentoring of junior faculty members involved in translational BMT studies.
Keratinocyte growth factor (KGF) is a protein that stimulates the grown of epithelial cells including those of the GI tract. Recombinant human KGF (rHuKGF) protects the GI tract, prevents severe GVHD and preserves donor T cell function needed for the beneficial graft-versus-leukemia effect. Specific aim 1 is to perform a single arm, dose-esclation, safety trial of rHuKGF plus standard GVHD prophylaxis.
Tumor Necrosis Factor (TNF)-alpha is a major inflammatory cytokine effector of these two disorders. Neutralization of TNF-alpha with soluble dimeric TNF-alpha binding protein (etanercept) can prevent both GVHD and acute lung injury in preclinical studies. Specific Aim 2 is to perform a single arm Phase I-II trial of etanercept plus standard treatment (steroids) to treat newly diagnosed GVHD. Specific Aim 3 is to perform a single-arm, open label Phase I-II study of etanercept plus standard treatment (steroids) to IPS after BMT.