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Blood, 15 March 2008, Vol. 111, No. 6, pp. 3276-3285. Prepublished online as a Blood First Edition Paper on October 9, 2007; DOI 10.1182/blood-2007-08-106286.
TRANSPLANTATION Biomarkers in newly diagnosed pediatric-extensive chronic graft-versus-host disease: a report from the Children's Oncology Group1 Children's Oncology Group, Division of Hematology/Oncology/Bone Marrow Transplantation, Department of Pediatrics, BC Children's Hospital/University of British Columbia, Vancouver, BC; 2 Children's Oncology Group, Department of Preventative Medicine, University of Southern California, Los Angeles; 3 Children's Oncology Group Operations Center, Arcadia, CA; 4 Medical Genetics, University of British Columbia, Vancouver, BC; 5 University of Iowa, Iowa City; 6 Division of Pediatric Oncology, Childrens Hospital of Philadelphia, PA; 7 Methodist Children's Hospital of South Texas, Texas Transplant Institute, San Antonio; and 8 University of North Carolina at Chapel Hill
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,
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| Copyright © 2008 by American Society of Hematology Online ISSN: 1528-0020 | |||||||||
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-2R
), 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 
