title: Biomarkers in newly diagnosed pediatric-extensive chronic graft-versus-host disease: a report from the Children's Oncology Group.
abstract: Numerous chronic graft-versus-host disease (cGVHD) biomarkers have been identified in limited, single-institution studies without validation. We hypothesized that plasma-derived biomarkers could diagnose, classify, and evaluate response in children with cGVHD. We performed a concomitant analysis of a number of known and predicted peripheral blood cGVHD biomarkers from a Children's Oncology Group (COG) phase 3 cGVHD therapeutic trial. A total of 52 newly diagnosed patients with extensive cGVHD were compared for time of onset after blood and marrow transplantation (BMT) (early, 3-8 months; late, > or = 9 months) with 28 time-matched controls with no cGVHD (early, 6 months after BMT; late, 12 months after BMT). Soluble B-cell activation factor (sBAFF), anti-dsDNA antibody, soluble IL-2 receptor alpha (sIL-2Ralpha), and soluble CD13 (sCD13) were elevated in patients with early-onset cGVHD compared with controls. sBAFF and anti-dsDNA were elevated in patients with late-onset cGVHD. Some of the biomarkers correlated with specific organ involvement and with therapeutic response. These 4 biomarkers had high specificity with higher sensitivity in combination. Changes in biomarker concentrations with immune reconstitution after transplantation significantly affected interpretation of results. The identified biomarkers have the potential for improved classification, early response evaluation, and direction of cGVHD treatment, but require validation in larger studies. This study is registered at www.cancer.gov/clinicaltrials as no. COG-ASCT0031.
authors.affiliation: Children's Oncology Group, Division of Hematology/Oncology/Bone Marrow Transplantation, Department of Pediatrics, BC Children's Hospital/University of British Columbia, Vancouver, BC, Canada.
authors.forename: Hisaki
authors.initials: H
authors.lastname: Fujii
authors.forename: Geoff
authors.initials: G
authors.lastname: Cuvelier
authors.forename: Kevin
authors.initials: K
authors.lastname: She
authors.forename: Soudabeh
authors.initials: S
authors.lastname: Aslanian
authors.forename: Hiromi
authors.initials: H
authors.lastname: Shimizu
authors.forename: Amina
authors.initials: A
authors.lastname: Kariminia
authors.forename: Mark
authors.initials: M
authors.lastname: Krailo
authors.forename: Zhengjia
authors.initials: Z
authors.lastname: Chen
authors.forename: Rob
authors.initials: R
authors.lastname: McMaster
authors.forename: Axel
authors.initials: A
authors.lastname: Bergman
authors.forename: Frederick
authors.initials: F
authors.lastname: Goldman
authors.forename: Stephen A
authors.initials: SA
authors.lastname: Grupp
authors.forename: Donna A
authors.initials: DA
authors.lastname: Wall
authors.forename: Andrew L
authors.initials: AL
authors.lastname: Gilman
authors.forename: Kirk R
authors.initials: KR
authors.lastname: Schultz
mesh_terms: D000293:Adolescent; D000328:Adult; D001323:Autoantibodies / Q000097:blood / Q000276:immunology; D001327:Autoimmune Diseases / Q000097:blood / Q000276:immunology; D015415:Biomarkers / Q000097:blood; D016026:Bone Marrow Transplantation; D002648:Child; D002675:Child, Preschool; D002908:Chronic Disease; D005260:Female; D006086:Graft vs Host Disease / Q000097:blood* / Q000175:diagnosis* / Q000188:drug therapy / Q000276:immunology; D006801:Humans; D007223:Infant; D008297:Male; D008495:Medical Oncology; D010372:Pediatrics; D011379:Prognosis; D040901:Proteomics; D012680:Sensitivity and Specificity; D013256:Steroids / Q000627:therapeutic use
chemical_list: D001323:Autoantibodies; D015415:Biomarkers; D013256:Steroids