Acute graft-versus-host disease (GVHD) is the primary limitation of allogeneic hematopoietic cell transplantation (HCT). There are currently no reliable diagnostic tests to predict the outcome of treatment, which correlate to long term survival. We have recently evaluated six previously validated diagnostic biomarkers of GVHD (IL2R?, TNFR1, HGF, IL8, elafin, and REG3?, for their ability to predict which patients would respond to therapy and who would achieve long term survival. We measured biomarker concentrations by from samples prospectively obtained at the initiation of treatment and day 28 following treatment in 112 patients who participated in a multicenter, randomized phase II clinical trial for newly diagnosed acute GVHD. We discovered an algorithm using values from all six biomarkers that predicted both day 28 response to treatment and mortality at day 180 from onset. This project will validate that algorithm by measuring all six biomarkers in a second group of 200 patients who patients who have recently participated in a multicenter, randomized phase II clinical trial for newly diagnosed acute GVHD. Awe will also develop a new algorithm by including a seventh biomarker that also predicts for response to treatment for GVHD. This algorithm will include both responses to treatment on day 28 after initiation of treatment as well as mortality at day 180 from the initiation of treatment.

Public Health Relevance

There are currently no laboratory tests to predict the outcome of treatment of graft versus host disease (GVHD) the major lethal complication of allogeneic bone marrow transplantation. We have recently discovered an algorithm using six serum biomarker values that we have previously validated that predicted both day 28 response to treatment and mortality at day 180 from onset. This project will validate that algorithm by measuring all six biomarkers in a second group of 200 patients who patients who have recently participated in a multicenter clinical trial for newly diagnosed acute GVHD.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Exploratory/Developmental Grants (R21)
Project #
1R21CA173459-01
Application #
8424381
Study Section
Transplantation, Tolerance, and Tumor Immunology (TTT)
Program Officer
Merritt, William D
Project Start
2013-08-01
Project End
2015-07-31
Budget Start
2013-08-01
Budget End
2014-07-31
Support Year
1
Fiscal Year
2013
Total Cost
$207,143
Indirect Cost
$73,932
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
Ferrara, James L M; Chaudhry, Mohammed S (2018) GVHD: biology matters. Hematology Am Soc Hematol Educ Program 2018:221-227
Hartwell, Matthew J; Ă–zbek, Umut; Holler, Ernst et al. (2017) An early-biomarker algorithm predicts lethal graft-versus-host disease and survival. JCI Insight 2:e89798
Renteria, Anne S; Levine, John E; Ferrara, James L M (2016) Therapeutic targets and emerging treatment options in gastrointestinal acute graft-versus-host disease. Expert Opin Orphan Drugs 4:469-484
Renteria, Anne S; Levine, John E; Ferrara, James L (2016) Development of a biomarker scoring system for use in graft-versus-host disease. Biomark Med 10:793-5
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
Levine, John E; Braun, Thomas M; Harris, Andrew C et al. (2015) A PROGNOSTIC SCORE FOR ACUTE GRAFT-VERSUS-HOST DISEASE BASED ON BIOMARKERS: A MULTICENTER STUDY. Lancet Haematol 2:e21-e29
Levine, John E; Braun, Thomas M; Harris, Andrew C et al. (2015) A prognostic score for acute graft-versus-host disease based on biomarkers: a multicentre study. Lancet Haematol 2:e21-9
Levine, John E; Hogan, William J; Harris, Andrew C et al. (2014) Improved accuracy of acute graft-versus-host disease staging among multiple centers. Best Pract Res Clin Haematol 27:283-7