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Acute graft-versus-host disease biomarkers measured during therapy can predict treatment outcomes: a Blood and Marrow Transplant Clinical Trials Network study. Blood 2012 Apr 19;119(16):3854-60 PMID: 22383800 PMCID: PMC3335389

Pubmed ID

22383800

DOI

10.1182/blood-2012-01-403063

Abstract

Acute graft-versus-host disease (GVHD) is the primary limitation of allogeneic hematopoietic cell transplantation, and once it develops, there are no reliable diagnostic tests to predict treatment outcomes. We hypothesized that 6 previously validated diagnostic biomarkers of GVHD (IL-2 receptor-α; tumor necrosis factor receptor-1; hepatocyte growth factor; IL-8; elafin, a skin-specific marker; and regenerating islet-derived 3-α, a gastrointestinal tract-specific marker) could discriminate between therapy responsive and nonresponsive patients and predict survival in patients receiving GVHD therapy. We measured GVHD biomarker concentrations from samples prospectively obtained at the initiation of treatment, day 14, and day 28, on a multicenter, randomized, 4-arm phase 2 clinical trial for newly diagnosed acute GVHD. We found that at each of 3 time points, GVHD onset, 2 weeks into treatment, and 4 weeks into treatment, a 6-protein biomarker panel predicted for the important clinical outcomes of day 28 posttherapy nonresponse and mortality at day 180 from onset. GVHD biomarker panels can be used for early identification of patients at high or low risk for treatment nonresponsiveness or death, and they may provide opportunities for early intervention and improved survival after hematopoietic cell transplantation. The study was registered in clinicaltrials.gov as NCT00224874.

Author List

Levine JE, Logan BR, Wu J, Alousi AM, Bolaños-Meade J, Ferrara JL, Ho VT, Weisdorf DJ, Paczesny S

Author

Brent R. Logan PhD Director, Professor in the Institute for Health and Equity department at Medical College of Wisconsin




Scopus

2-s2.0-84860345135   107 Citations

MESH terms used to index this publication - Major topics in bold

Acute Disease
Adult
Aged
Biomarkers
Bone Marrow Transplantation
Elafin
Female
Graft vs Host Disease
Hepatocyte Growth Factor
Humans
Immunosuppressive Agents
Interleukin-8
Logistic Models
Male
Middle Aged
Pancreatitis-Associated Proteins
Predictive Value of Tests
Prognosis
Proteins
Randomized Controlled Trials as Topic
Receptors, Interleukin-2
Tumor Necrosis Factor-alpha
Young Adult
jenkins-FCD Prod-331 a335b1a6d1e9c32173c9534e6f6ff51494143916