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 #
5P01CA018029-38
Application #
8550767
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
2013-09-12
Budget End
2014-06-30
Support Year
38
Fiscal Year
2013
Total Cost
$3,971,921
Indirect Cost
$1,707,029
Name
Fred Hutchinson Cancer Research Center
Department
Type
DUNS #
078200995
City
Seattle
State
WA
Country
United States
Zip Code
98109
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Walter, R B; Gyurkocza, B; Storer, B E et al. (2015) Comparison of minimal residual disease as outcome predictor for AML patients in first complete remission undergoing myeloablative or nonmyeloablative allogeneic hematopoietic cell transplantation. Leukemia 29:137-44
Walter, Roland B; Sandmaier, Brenda M; Storer, Barry E et al. (2015) Number of courses of induction therapy independently predicts outcome after allogeneic transplantation for acute myeloid leukemia in first morphological remission. Biol Blood Marrow Transplant 21:373-8
Mielcarek, Marco; Kirkorian, Anna Yasmine; Hackman, Robert C et al. (2014) Langerhans cell homeostasis and turnover after nonmyeloablative and myeloablative allogeneic hematopoietic cell transplantation. Transplantation 98:563-8
Hoffmeister, Paul A; Storer, Barry E; Baker, K Scott et al. (2014) Nephrolithiasis in pediatric hematopoietic cell transplantation with up to 40 years of follow-up. Pediatr Blood Cancer 61:417-23
Stromnes, Ingunn M; Schmitt, Thomas M; Chapuis, Aude G et al. (2014) Re-adapting T cells for cancer therapy: from mouse models to clinical trials. Immunol Rev 257:145-64
Boyle, Nicole M; Podczervinski, Sara; Jordan, Kim et al. (2014) Bacterial foodborne infections after hematopoietic cell transplantation. Biol Blood Marrow Transplant 20:1856-61
Li, Xiang; Deeg, H Joachim (2014) Murine xenogeneic models of myelodysplastic syndrome: an essential role for stroma cells. Exp Hematol 42:4-10
Fisher, C E; Stevens, A M; Leisenring, W et al. (2014) Independent contribution of bronchoalveolar lavage and serum galactomannan in the diagnosis of invasive pulmonary aspergillosis. Transpl Infect Dis 16:505-10
Raj, Kavita; Pagliuca, Antonio; Bradstock, Kenneth et al. (2014) Peripheral blood hematopoietic stem cells for transplantation of hematological diseases from related, haploidentical donors after reduced-intensity conditioning. Biol Blood Marrow Transplant 20:890-5

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