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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.
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Submitted August 9, 2007
Accepted September 28, 2007
Biomarkers in newly diagnosed pediatric extensive chronic graft-versus-host disease: a report from the Children's Oncology Group
Hisaki Fujii, Geoff Cuvelier, Kevin She, Soudabeh Aslanian, Hiromi Shimizu, Amina Kariminia, Mark Krailo, Zhengjia Chen, Rob McMaster, Axel Bergman, Frederick Goldman, Stephen A. Grupp, Donna A. Wall, Andrew L. Gilman, and Kirk R. Schultz*
Div. of Hematology/Oncology/BMT, Department of Pediatrics, BC Children's Hospital/UBC, Vancouver, BC, Canada
Department of Preventative Medicine, Children's Oncology Group, University of Southern California, Los Angeles, Ca, United States
Children's Oncology Group Operations Center, Arcadia, CA, United States
Medical Genetics, University of British Columbia, Vancouver, BC, Canada
Stem Cell Transplantation, University of Iowa, Iowa City, IA, United States
Division of Pediatric Oncology, Children's Hospital of Philadelphia, Philadelphia, PA, United States
Methodist Children's Hospital of South Texas, Texas Transplant Institute, San Antonio, TX, United States
Stem Cell Transplantation, University of North Carolina at Chapel Hill, Chapel Hill, NC, United States
* Corresponding author; email: kschultz{at}interchange.ubc.ca.
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 III cGVHD therapeutic trial. Fifty-two newly diagnosed, extensive cGVHD patients were compared for time of onset after blood and marrow transplantation (BMT) (early- 3 to 8 months and late - 9 months) with 28 time-matched controls with no cGVHD (6 months - early and 12 months - late after BMT). Soluble BAFF (sBAFF), anti-dsDNA antibody, soluble IL-2 receptor alpha (sIL-2R ), and soluble CD13 (sCD13) were elevated in early onset cGVHD compared to controls. Soluble BAFF and anti-dsDNA were elevated in late onset cGVHD. Some of the biomarkers correlated with specific organ involvement and with therapeutic response. These four 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 #COG-ASCT0031.
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