title: Acute graft-versus-host disease biomarkers measured during therapy can predict treatment outcomes: a Blood and Marrow Transplant Clinical Trials Network study.
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.
authors.affiliation: University of Michigan Blood and Marrow Transplant Program, Ann Arbor, USA. jelevine@med.umich.edu
authors.forename: John E
authors.initials: JE
authors.lastname: Levine
authors.forename: Brent R
authors.initials: BR
authors.lastname: Logan
authors.forename: Juan
authors.initials: J
authors.lastname: Wu
authors.forename: Amin M
authors.initials: AM
authors.lastname: Alousi
authors.forename: Javier
authors.initials: J
authors.lastname: Bolaños-Meade
authors.forename: James L M
authors.initials: JL
authors.lastname: Ferrara
authors.forename: Vincent T
authors.initials: VT
authors.lastname: Ho
authors.forename: Daniel J
authors.initials: DJ
authors.lastname: Weisdorf
authors.forename: Sophie
authors.initials: S
authors.lastname: Paczesny
mesh_terms: D000208:Acute Disease; D000328:Adult; D000368:Aged; D015415:Biomarkers / Q000378:metabolism; D016026:Bone Marrow Transplantation / Q000009:adverse effects* / Q000401:mortality*; D053492:Elafin / Q000378:metabolism; D005260:Female; D006086:Graft vs Host Disease / Q000276:immunology / Q000378:metabolism* / Q000401:mortality* / Q000628:therapy; D017228:Hepatocyte Growth Factor / Q000378:metabolism; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use; D016209:Interleukin-8 / Q000378:metabolism; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D000073718:Pancreatitis-Associated Proteins; D011237:Predictive Value of Tests; D011379:Prognosis; D011506:Proteins / Q000378:metabolism; D016032:Randomized Controlled Trials as Topic; D015375:Receptors, Interleukin-2 / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D055815:Young Adult
chemical_list: D015415:Biomarkers; C508606:CXCL8 protein, human; D053492:Elafin; C066855:HGF protein, human; D007166:Immunosuppressive Agents; D016209:Interleukin-8; C506806:PI3 protein, human; D000073718:Pancreatitis-Associated Proteins; D011506:Proteins; C494437:REG3G protein, human; D015375:Receptors, Interleukin-2; D014409:Tumor Necrosis Factor-alpha; D017228:Hepatocyte Growth Factor