Chronic graft vs. host disease (GVHD) occurs in the majority of survivors of allogeneic hematopoietic cell transplantation (HCT). The syndrome is the major source of non-relapse mortality among two year disease-free survivors, and results in increased symptom burden, functional disability, and impaired quality of life. Therapy of established chronic GVHD is unsuccessful in many cases, and can be associated with toxicity and death due to treatment complications. Rational selection of therapy for any given patient is not possible based on current evidence, and it can be difficult to identify non-responders early in the course of therapy based on clinical judgment. We propose combining cutting edge laboratory techniques with detailed phenotypic data to identify biologic markers predictive of treatment success. The parent R01-funded Chronic GVHD Consortium cohort study will provide rich chronic GVHD response data and allied biospecimens to facilitate this work. In our proposed study, we will identify transcriptional markers of therapeutic response, and verify these findings in an independent patient cohort matched for potentially confounding clinical variables. This work has great promise to identify clinically relevant markers of non-response, and identify mechanisms of therapy resistance that may lead to rational targets for future interventional trials in chronic GVHD.
Chronic graft vs. host disease (GVHD) is a serious obstacle to the otherwise curative potential of blood or bone marrow transplant for cancers such as leukemia and lymphoma. It represents the major cause of late transplant-related death, suffering, and impaired quality of life. One of the major challenges is inability to determine whic patients will respond well to available treatments for chronic GVHD. The goal of this study is to identify biologic markers of response to treatment that can be measured in the blood. This work has great potential to facilitate an individualized approach to chronic GVHD treatment, and through discovery of mechanisms of resistance to therapy, lead to the development of targeted novel therapies in chronic GVHD.
