The overall goal of this program project grant (PPG) continues to be the exploration of the cellular and molecular mechanisms of allogeneic bone marrow transplantation (BMT) and to serve as a translational research platform for novel therapeutic strategies for patients with hematologic malignancies. Graft versus host disease (GVHD) remains a major cause of morbility and mortality after allogeneic BMT and prevents this curative therapy from wider application in cancer patients;thus a long term goal for the entire area of BMT is to develop new strategies to separate a beneficial graft versus leukemia (GVL) effect from GVHD. This PPG contributes to that goal by: 1) exploring the cellular and molecular mechanisms of GVHD from several perspectives;and 2) functioning as a translational research platform for the application of these mechanistic insights in Phase l/ll clinical trials in BMT patients. The significance of these studies therefore lies in their potential to lead to novel therapies for cancer patients, particularly those with hematologic malignancies. The major theme of this PPG is the modulation of donor immune responses to allogeneic host tissues without removal of T cells from the donor graft. This theme of modulating the interactions among the cellular subpopulations that initiate and mediate GVHD develops in several ways and unifies the entire PPG increasing collaborations and interactions among project leaders and provides multiple opportunities for synergy. In this next cycle, the PPG components continue as three projects and three cores: Project 1 HDAC Inhibition to Prevent GVHD Project 2 A Novel Bioenergetic Strategy to Treat GVHD Project 3 GVHD Clinical Trials and Biomarkers Core A Administration and Biostatistics Core B Experimental BMT Core C Clinical Sample Database and Proteomics

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Program Projects (P01)
Project #
5P01CA039542-25
Application #
8331344
Study Section
Special Emphasis Panel (ZCA1-RPRB-J (M1))
Program Officer
Merritt, William D
Project Start
1997-09-10
Project End
2015-08-31
Budget Start
2012-09-01
Budget End
2013-08-31
Support Year
25
Fiscal Year
2012
Total Cost
$1,665,263
Indirect Cost
$560,322
Name
University of Michigan Ann Arbor
Department
Pediatrics
Type
Schools of Medicine
DUNS #
073133571
City
Ann Arbor
State
MI
Country
United States
Zip Code
48109
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Choi, Sung Won; Braun, Thomas; Chang, Lawrence et al. (2014) Vorinostat plus tacrolimus and mycophenolate to prevent graft-versus-host disease after related-donor reduced-intensity conditioning allogeneic haemopoietic stem-cell transplantation: a phase 1/2 trial. Lancet Oncol 15:87-95
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Levine, John E; Huber, Elisabeth; Hammer, Suntrea T G et al. (2013) Low Paneth cell numbers at onset of gastrointestinal graft-versus-host disease identify patients at high risk for nonrelapse mortality. Blood 122:1505-9
Harris, Andrew C; Kitko, Carrie L; Couriel, Daniel R et al. (2013) Extramedullary relapse of acute myeloid leukemia following allogeneic hematopoietic stem cell transplantation: incidence, risk factors and outcomes. Haematologica 98:179-84
Brown, J R; Kim, H T; Armand, P et al. (2013) Long-term follow-up of reduced-intensity allogeneic stem cell transplantation for chronic lymphocytic leukemia: prognostic model to predict outcome. Leukemia 27:362-9
Paczesny, Sophie (2013) Discovery and validation of graft-versus-host disease biomarkers. Blood 121:585-94

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