Approximately 30-50% of people undergoing allogeneic hematopoietic cell transplantation (HCT) will develop chronic graft-versus-host disease (GVHD), a syndrome characterized by multi-system inflammation and fibrosis that clinically resembles autoimmune diseases. Chronic GVHD is the leading cause of non-relapse mortality in two-year disease free survivors and a major cause of morbidity. In 2005, the NIH convened a consensus conference designed to improve clinical research methods in chronic GVHD. Recommendations from the conference have been published, and are called the "NIH consensus criteria." During our previous funding period, we assembled a multi-center, longitudinal, observational study of 554 patients who were assessed every six months to test the NIH consensus criteria. We have published 6 papers (12 more submitted or in preparation) evaluating the consensus recommendations. Our results support the recommended definitions for chronic GVHD diagnosis and severity scoring. Specifically, we confirmed the poor prognosis associated with concurrent acute and chronic GVHD (overlap syndrome) and showed a higher non-relapse mortality and lower overall survival associated with moderate-severe chronic GVHD. However, our analyses did not support the recommended NIH measures to assess therapeutic response. In particular, calculated overall NIH response at 6 months correlated poorly with patient and provider-reported responses, and also did not predict subsequent non-relapse mortality and overall survival. Thus, if a new, promising treatment for chronic GVHD were available, the field does not have a validated measure that can serve as a primary endpoint in a clinical trial. To address this critical gap in the field, we propose developing two new tools, the chronic GVHD activity index (CGVHD-AI) and the chronic GVHD severity score (CGVHD-SS). The CGVHD-AI is intended for use as an overall measure of disease activity, so that change in the score from enrollment to follow-up reflects treatment effects. The CGVHD- SS is intended to serve as an intermediate endpoint that predicts eventual treatment success, even if that takes months to years to reach. Eleven centers will enroll 368 patients with chronic GVHD who are just starting initial or secondary therapy. Comprehensive assessments at enrollment and 6 months will collect the candidate patient-reported, provider-reported, and laboratory tests that will be considered for inclusion in the new measures. At 18 months after enrollment, patients will again be assessed with all measures. Using this information, we will develop and validate the CGVHD-AI and CGVHD-SS, thus allowing robust clinical trials in chronic GVHD.

Public Health Relevance

Chronic graft-versus-host disease (GVHD) is a serious complication that occurs when the bone marrow or stem cells from one person are transplanted into another person, usually for the treatment of a blood cancer or other blood disease. Chronic GVHD is the leading cause of death in people who are otherwise cured of their cancers, and it is a major predictor of poor quality of life and impaired ability to function. The goal of this study s to develop better methods to quickly and accurately determine if people are responding to treatment for chronic GVHD.

National Institute of Health (NIH)
National Cancer Institute (NCI)
Research Project (R01)
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Clinical Oncology Study Section (CONC)
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Merritt, William D
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Fred Hutchinson Cancer Research Center
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Inamoto, Yoshihiro; Flowers, Mary E D; Sandmaier, Brenda M et al. (2014) Failure-free survival after initial systemic treatment of chronic graft-versus-host disease. Blood 124:1363-71
Chow, Eric J; Baker, K Scott; Lee, Stephanie J et al. (2014) Influence of conventional cardiovascular risk factors and lifestyle characteristics on cardiovascular disease after hematopoietic cell transplantation. J Clin Oncol 32:191-8
El-Jawahri, Areej; Pidala, Joseph; Inamoto, Yoshi et al. (2014) Impact of age on quality of life, functional status, and survival in patients with chronic graft-versus-host disease. Biol Blood Marrow Transplant 20:1341-8
Inamoto, Yoshihiro; Pidala, Joseph; Chai, Xiaoyu et al. (2014) Assessment of joint and fascia manifestations in chronic graft-versus-host disease. Arthritis Rheumatol 66:1044-52
Palmer, Jeanne; Williams, Kirsten; Inamoto, Yoshihiro et al. (2014) Pulmonary symptoms measured by the national institutes of health lung score predict overall survival, nonrelapse mortality, and patient-reported outcomes in chronic graft-versus-host disease. Biol Blood Marrow Transplant 20:337-44
Kitko, Carrie L; Levine, John E; Storer, Barry E et al. (2014) Plasma CXCL9 elevations correlate with chronic GVHD diagnosis. Blood 123:786-93
Allen, Jessica L; Tata, Prasanthi V; Fore, Matthew S et al. (2014) Increased BCR responsiveness in B cells from patients with chronic GVHD. Blood 123:2108-15
Inamoto, Y; Jagasia, M; Wood, W A et al. (2014) Investigator feedback about the 2005 NIH diagnostic and scoring criteria for chronic GVHD. Bone Marrow Transplant 49:532-8
Inamoto, Yoshihiro; Martin, Paul J; Storer, Barry E et al. (2014) Association of severity of organ involvement with mortality and recurrent malignancy in patients with chronic graft-versus-host disease. Haematologica 99:1618-23
Pidala, Joseph; Chai, Xiaoyu; Martin, Paul et al. (2013) Hand grip strength and 2-minute walk test in chronic graft-versus-host disease assessment: analysis from the Chronic GVHD Consortium. Biol Blood Marrow Transplant 19:967-72

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