Allogeneic hematopoietic stem cell transplantation (HSCT) is the only curative therapy for many patients with hematologic malignancies and marrow failure. A critical hurdle in accomplishment of successful HSCT has been graft-versus-host disease (GVHD).The ultimate objective of the research projects in this renewal application is to further improve our understanding of the pathophysiology of aGVHD and cGVHD and to develop novel strategies for both prevention and therapy of cGVHD by targeting distinct cellular populations in these two syndromes while maintaining GVL. Key to achieve this objective and thus to lead to the success of this program project is dynamic biostatistical collaboration with individuals in each of the 3 projects and the 3 other Cores. The purpose of the Biostatistics Core C is to provide the following services that will be utilized by the research projects included in this Program Project. 1. To provide biostatistical collaboration for translational clinical research studies. 2. To provide biostatistical collaboration for translational animal research studies. 3. To provide biostatistical and/or bioinformatics collaboration for translational laboratory research studies. 4. To provide research infrastructure for translational research. 5. To provide computing resources for data processing, and statistical analysis, standardized reporting, and quality control.

Public Health Relevance

Preventing or treating cGVHD, thus reducing related morbidity and mortality, is important because 1) improvements in HSCT technology allow the use of older donors and older patients to receive transplant, thus more patients undergo HSCT, and 2) improvements in supportive care result in better survival in later time periods when cGVHD occurs.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Program Projects (P01)
Project #
5P01CA142106-10
Application #
8468140
Study Section
Heart, Lung, and Blood Initial Review Group (HLBP)
Project Start
Project End
2015-03-31
Budget Start
2013-04-01
Budget End
2014-03-31
Support Year
10
Fiscal Year
2013
Total Cost
$203,783
Indirect Cost
$69,895
Name
Dana-Farber Cancer Institute
Department
Type
DUNS #
076580745
City
Boston
State
MA
Country
United States
Zip Code
02215
Borges, Christopher M; Reichenbach, Dawn K; Kim, Beom Seok et al. (2016) Regulatory T cell expressed MyD88 is critical for prolongation of allograft survival. Transpl Int 29:930-40
Armand, Philippe; Kim, Haesook T; Sainvil, Marie-Michele et al. (2016) The addition of sirolimus to the graft-versus-host disease prophylaxis regimen in reduced intensity allogeneic stem cell transplantation for lymphoma: a multicentre randomized trial. Br J Haematol 173:96-104
Alho, Ana C; Kim, Haesook T; Chammas, Marie J et al. (2016) Unbalanced recovery of regulatory and effector T cells after allogeneic stem cell transplantation contributes to chronic GVHD. Blood 127:646-57
Schönle, Anne; Hartl, Frederike A; Mentzel, Jan et al. (2016) Caveolin-1 regulates TCR signal strength and regulatory T-cell differentiation into alloreactive T cells. Blood 127:1930-9
Flynn, Ryan; Paz, Katelyn; Du, Jing et al. (2016) Targeted Rho-associated kinase 2 inhibition suppresses murine and human chronic GVHD through a Stat3-dependent mechanism. Blood 127:2144-54
Zeiser, Robert; Blazar, Bruce R (2016) Preclinical models of acute and chronic graft-versus-host disease: how predictive are they for a successful clinical translation? Blood 127:3117-26
Kim, Haesook T; Zhang, Mei-Jie; Woolfrey, Ann E et al. (2016) Donor and recipient sex in allogeneic stem cell transplantation: what really matters. Haematologica 101:1260-1266
Souroullas, George P; Jeck, William R; Parker, Joel S et al. (2016) An oncogenic Ezh2 mutation induces tumors through global redistribution of histone 3 lysine 27 trimethylation. Nat Med 22:632-40
Koreth, John; Kim, Haesook T; Jones, Kyle T et al. (2016) Efficacy, durability, and response predictors of low-dose interleukin-2 therapy for chronic graft-versus-host disease. Blood 128:130-7
Hirakawa, Masahiro; Matos, Tiago; Liu, Hongye et al. (2016) Low-dose IL-2 selectively activates subsets of CD4(+) Tregs and NK cells. JCI Insight 1:e89278

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