Acute graft-versus-host disease biomarkers measured during therapy can predict treatment outcomes: a Blood and Marrow Transplant Clinical Trials Network study.

Pubmed ID: 22383800

Pubmed Central ID: PMC3335389

Journal: Blood

Publication Date: April 19, 2012

Affiliation: University of Michigan Blood and Marrow Transplant Program, Ann Arbor, USA. jelevine@med.umich.edu

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

Grants: 065528, U01HL069294, U10 HL069249, U10 HL069294, U10 HL069301, U10 HL069330, U10 HL069348, U24 CA076518, U01 HL069294, U10 HL069290

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

Cite As: Levine JE, Logan BR, Wu J, Alousi AM, Bolaños-Meade J, Ferrara JL, Ho VT, Weisdorf DJ, Paczesny S. 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. Epub 2012 Mar 1.

Studies:

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.