Chronic graft-versus-host disease

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This effort continues to be very productive as evidenced by the yearly publication output related to GVHD, inclugin publication of the Branch initiated imatinib clinical trial (see below). In addition, I have made several important contributions to the identification of novel skin manifestations of cGVHD, as well as identified the role of total body irradiation as a risk factor for cGVHD. In press is a report describing autoimmune skin manifestations of cutaneous GVHD and a link to female hematopoeitic cell donor. In addition, this group has developed a national reputation as a referral center for challenging cases to be evaluated from around the country. Imatinib mesylate is a tyrosine kinase inhibitor that was specifically developed to target inhibition of tyrosine phosphorylation of proteins involved in BCR-ABL signal transduction. It additionally has a high degree of specificity and biological activity against both platelet-derived growth factor (PDGF) and transforming growth factor- (TGF-) signaling pathways, cytokines strongly implicated in the fibrogenesis process. Patients in this trial were recruited nationwide and treated and evaluated in the cGVHD Multidisciplinary Program at the National Cancer Institute/National Institutes of Health. In evaluating an exceedingly complex disease with a diverse patient population, cGVHD clinical trials suffer from poor standardization of entry and response-assessment criteria. This has resulted in difficulties in clinical trial data interpretation. Diagnosis and response assessment are based on the NIH Consensus Development Project on Criteria for Clinical Trials in Chronic Graft-Versus-Host Disease criteria and is focused on well-defined cGVHD organ manifestations with clearly defined entry, concurrent treatment, and evaluation criteria. To date all patients have met the primary outcome (6 month) endpoint of the trial and will are currently collecting the laboratory and other research study data in preparion of a final manuscript.