Biomarkers in newly diagnosed pediatric-extensive chronic graft-versus-host disease: a report from the Children's Oncology Group.
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.
Fujii
Hisaki
H
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.
Cuvelier
Geoff
G
She
Kevin
K
Aslanian
Soudabeh
S
Shimizu
Hiromi
H
Kariminia
Amina
A
Krailo
Mark
M
Chen
Zhengjia
Z
McMaster
Rob
R
Bergman
Axel
A
Goldman
Frederick
F
Grupp
Stephen A
SA
Wall
Donna A
DA
Gilman
Andrew L
AL
Schultz
Kirk R
KR
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
D001323:Autoantibodies; D015415:Biomarkers; D013256:Steroids