The overall goal of this program project is to improve allogeneic hematopoietic cell transplantation (HCT) as treatment for hematological malignancies. Specifically we proposed laboratory and clinical studies to broaden the availability of transplantation, to decrease the incidence and severity of graft-versus-host disease, and to reduce the incidence of malignant disease recurrence post transplant. Four individual projects are proposed: 1. Immunogenetics of Graft-versus-host Disease. 2. Nonmyeloablative Hematopoietic Cell Allotransplants. 3. Specific Adoptive Immunotherapy of Myeloid Malignancy. 4. Targeting T Cell Reactivity for Leukemia Eradication. In addition, core support is requested in biostatistics, molecular diagnostics, cell processing, long-term follow-up, and administration. Our ability to successfully carry out the proposed work is greatly benefited by: (1) the existence of a large group of investigators all focused on the general topic of HCT;(2) strong preclinical research programs at our Center in support of this topic;and, (3) treatment of >500 transplant patients at our Center each year

Public Health Relevance

The Program Project has direct relevance to the >27,000 patients who undergo allogeneic HCT for treatment of hematopoietic malignancies each year. The work proposed promises to increase the availability of transplantation and to make it safer and more effective. Lessons learned from our planned studies will apply to issues of transplant tolerance, the molecular basis of malignant disease progression, and especially the immunotherapy of cancer.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Program Projects (P01)
Project #
5P01CA018029-39
Application #
8733521
Study Section
Special Emphasis Panel (ZCA1-GRB-T (M1))
Program Officer
Merritt, William D
Project Start
1997-12-22
Project End
2017-06-30
Budget Start
2014-07-01
Budget End
2015-06-30
Support Year
39
Fiscal Year
2014
Total Cost
$4,098,686
Indirect Cost
$1,761,510
Name
Fred Hutchinson Cancer Research Center
Department
Type
DUNS #
078200995
City
Seattle
State
WA
Country
United States
Zip Code
98109
Humbert, Olivier; Gisch, Don W; Wohlfahrt, Martin E et al. (2016) Development of Third-generation Cocal Envelope Producer Cell Lines for Robust Lentiviral Gene Transfer into Hematopoietic Stem Cells and T-cells. Mol Ther 24:1237-46
Mielcarek, Marco; Furlong, Terry; O'Donnell, Paul V et al. (2016) Posttransplantation cyclophosphamide for prevention of graft-versus-host disease after HLA-matched mobilized blood cell transplantation. Blood 127:1502-8
Achille, Nicholas J; Othus, Megan; Phelan, Kathleen et al. (2016) Association between early promoter-specific DNA methylation changes and outcome in older acute myeloid leukemia patients. Leuk Res 42:68-74
Cheng, Guang-Shing; Campbell, Angela P; Xie, Hu et al. (2016) Correlation and Agreement of Handheld Spirometry with Laboratory Spirometry in Allogeneic Hematopoietic Cell Transplant Recipients. Biol Blood Marrow Transplant 22:925-31
Festuccia, Moreno; Deeg, H Joachim; Gooley, Theodore A et al. (2016) Minimal Identifiable Disease and the Role of Conditioning Intensity in Hematopoietic Cell Transplantation for Myelodysplastic Syndrome and Acute Myelogenous Leukemia Evolving from Myelodysplastic Syndrome. Biol Blood Marrow Transplant 22:1227-33
Green, Margaret L; Leisenring, Wendy; Xie, Hu et al. (2016) Cytomegalovirus viral load and mortality after haemopoietic stem cell transplantation in the era of pre-emptive therapy: a retrospective cohort study. Lancet Haematol 3:e119-27
Sedlak, Ruth Hall; Hill, Joshua A; Nguyen, Thuy et al. (2016) Detection of Human Herpesvirus 6B (HHV-6B) Reactivation in Hematopoietic Cell Transplant Recipients with Inherited Chromosomally Integrated HHV-6A by Droplet Digital PCR. J Clin Microbiol 54:1223-7
Graf, Solomon A; Vaughn, Jennifer E; Chauncey, Thomas R et al. (2016) Comorbidities, Alcohol Use Disorder, and Age Predict Outcomes after Autologous Hematopoietic Cell Transplantation for Lymphoma. Biol Blood Marrow Transplant 22:1582-7
Aki, S Z; Inamoto, Y; Carpenter, P A et al. (2016) Confounding factors affecting the National Institutes of Health (NIH) chronic Graft-Versus-Host Disease Organ-Specific Score and global severity. Bone Marrow Transplant 51:1350-1353
Gallo, S; Woolfrey, A E; Burroughs, L M et al. (2016) Marrow grafts from HLA-identical siblings for severe aplastic anemia: does limiting the number of transplanted marrow cells reduce the risk of chronic GvHD? Bone Marrow Transplant 51:1573-1578

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