Acute graft versus host disease (GHVD) remains a major source of morbidity and transplant-related mortality (TRM) after allogeneic hematopoietic stem cell transplantation (HCT). Despite advances in GVHD prophylactic regimen, significant (grade II-IV) acute GVHD that requires systemic treatment with high dose steroids occurs in 50-70% of HCT recipients of transplants from HLA-matched unrelated donor or partially HLA-matched donors. Outcomes for patients developing acute GVHD remain poor and new prophylactic strategies are needed. The University of Michigan BMT program has made seminal contributions to the understanding of GVHD pathophysiology and to the translation of promising new approaches into clinical trials. The University of Michigan was chosen to be a charter member of the BMT CTN at its inception ten years ago, and it has made key contributions to the success of the network, including a chairmanship of the steering committee, chairmanships of two protocols, additional memberships in six protocols, and the organization and hosting of the highly successful State of the Science Symposium in 2007. This application proposes, in specific Aim I, the comparison of two novel GVHD prophylaxis-required (etanercept vs pentostatin/ATG) in a multicenter, randomized Phase II protocol, the preliminary data for which having been generated at the University of Michigan and MD Anderson.
Specific Aim 2 proposes to validate a four biomarker panel (IL2Rd, TNFRI, Elafin and Reg3a) for its ability to predict the onset of GVHD from plasma samples taken early after transplant from patients participating in the proposed trial. If validated, this biomarker panel could be used in subsequent BMT CTN trials to guide the preemptive treatment of acute GVHD.

Public Health Relevance

This grant will make the University of Michigan a Core Center for the BMT CTN in order to conduct multi- center clinical trials in BMT patients.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Cooperative Clinical Research--Cooperative Agreements (U10)
Project #
5U10HL069330-13
Application #
8479410
Study Section
Special Emphasis Panel (ZHL1-CSR-K (M3))
Program Officer
Di Fronzo, Nancy L
Project Start
2001-09-30
Project End
2017-06-30
Budget Start
2013-07-01
Budget End
2014-06-30
Support Year
13
Fiscal Year
2013
Total Cost
$160,943
Indirect Cost
$57,443
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
Harris, Andrew C; Ferrara, James L M; Levine, John E (2013) Advances in predicting acute GVHD. Br J Haematol 160:288-302