Abstract

) Our preliminary data demonstrate that the intensity of the conditioning regimen correlates with systemic levels of endotoxin, TNFalpha and IL-1 which significantly amplify GVHD. Using murine BMT models, we propose to investigate novel strategies to modulate this cytokine cascade, and to determine the extent to which individual target organ pathology correlates with changes in systemic GVHD.
Our specific aims are: 1) To evaluate the ability of IL-I 1 and keratinocyte growth factor to prevent GVHD after intensively conditioned allogeneic BMT. 2) To compare conditioning regimens prior to allogeneic BMT for their effects on inflammatory cytokines. 3) To analyze blockade of inflammatory cytokines (both directly and indirectly) as a strategy to separate GVL from GVHD.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Program Projects (P01)
Project #
5P01CA039542-14
Application #
6318277
Study Section
Project Start
2000-06-01
Project End
2001-04-30
Budget Start
Budget End
Support Year
14
Fiscal Year
2000
Total Cost
$310,115
Indirect Cost

  Institution

Name
Dana-Farber Cancer Institute
Department
Type
DUNS #
149617367
City
Boston
State
MA
Country
United States
Zip Code
02215

  Publications

Holtan, Shernan G; DeFor, Todd E; Panoskaltsis-Mortari, Angela et al. (2018) Amphiregulin modifies the Minnesota Acute Graft-versus-Host Disease Risk Score: results from BMT CTN 0302/0802. Blood Adv 2:1882-1888
Ortiz-Velez, Laura; Ortiz-Villalobos, Javiera; Schulman, Abby et al. (2018) Genome alterations associated with improved transformation efficiency in Lactobacillus reuteri. Microb Cell Fact 17:138
Ferrara, James L M; Chaudhry, Mohammed S (2018) GVHD: biology matters. Hematology Am Soc Hematol Educ Program 2018:221-227
Major-Monfried, Hannah; Renteria, Anne S; Pawarode, Attaphol et al. (2018) MAGIC biomarkers predict long-term outcomes for steroid-resistant acute GVHD. Blood 131:2846-2855
Naymagon, Steven; Naymagon, Leonard; Wong, Serre-Yu et al. (2017) Acute graft-versus-host disease of the gut: considerations for the gastroenterologist. Nat Rev Gastroenterol Hepatol 14:711-726
Hartwell, Matthew J; Özbek, Umut; Holler, Ernst et al. (2017) An early-biomarker algorithm predicts lethal graft-versus-host disease and survival. JCI Insight 2:e89798
Stickel, N; Hanke, K; Marschner, D et al. (2017) MicroRNA-146a reduces MHC-II expression via targeting JAK/STAT signaling in dendritic cells after stem cell transplantation. Leukemia 31:2732-2741
Ferrara, James Lm; Smith, Christopher M; Sheets, Julia et al. (2017) Altered homeostatic regulation of innate and adaptive immunity in lower gastrointestinal tract GVHD pathogenesis. J Clin Invest 127:2441-2451
Miller, Holly K; Braun, Thomas M; Stillwell, Terri et al. (2017) Infectious Risk after Allogeneic Hematopoietic Cell Transplantation Complicated by Acute Graft-versus-Host Disease. Biol Blood Marrow Transplant 23:522-528
Harris, Andrew C; Young, Rachel; Devine, Steven et al. (2016) International, Multicenter Standardization of Acute Graft-versus-Host Disease Clinical Data Collection: A Report from the Mount Sinai Acute GVHD International Consortium. Biol Blood Marrow Transplant 22:4-10

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