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-b 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.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Investigator-Initiated Intramural Research Projects (ZIA)
Project #
1ZIABC011549-04
Application #
9556624
Study Section
Project Start
Project End
Budget Start
Budget End
Support Year
4
Fiscal Year
2017
Total Cost
Indirect Cost
Name
Basic Sciences
Department
Type
DUNS #
City
State
Country
Zip Code
Goklemez, Sencer; Pirsl, Filip; Curtis, Lauren M et al. (2017) Clinical significance of IgE in a large cohort of patients with moderate or severe chronic graft-versus-host disease. Am J Hematol 92:E162-E164
Hakim, Frances T; Memon, Sarfraz; Jin, Ping et al. (2016) Upregulation of IFN-Inducible and Damage-Response Pathways in Chronic Graft-versus-Host Disease. J Immunol 197:3490-3503
Imanguli, Matin M; Atkinson, Jane C; Mitchell, Sandra A et al. (2016) Erratum to ""Salivary Gland Involvement in Chronic Graft-versus-Host Disease: Prevalence, Clinical Significance, and Recommendations for Evaluation"" [Biol Blood Marrow Transplant 16:1362-1369]. Biol Blood Marrow Transplant 22:1147
Cowen, Edward West (2016) Graft-vs-Host Disease. JAMA Dermatol 152:356
Bassim, C W; Fassil, H; Mays, J W et al. (2015) Oral disease profiles in chronic graft versus host disease. J Dent Res 94:547-54
Jagasia, Madan H; Greinix, Hildegard T; Arora, Mukta et al. (2015) National Institutes of Health Consensus Development Project on Criteria for Clinical Trials in Chronic Graft-versus-Host Disease: I. The 2014 Diagnosis and Staging Working Group report. Biol Blood Marrow Transplant 21:389-401.e1
Kuzmina, Zoya; Gounden, Verena; Curtis, Lauren et al. (2015) Clinical significance of autoantibodies in a large cohort of patients with chronic graft-versus-host disease defined by NIH criteria. Am J Hematol 90:114-9
Zuo, Rena C; Naik, Haley B; Steinberg, Seth M et al. (2015) Risk factors and characterization of vitiligo and alopecia areata in patients with chronic graft-vs-host disease. JAMA Dermatol 151:23-32
Baird, Kristin; Comis, Leora E; Joe, Galen O et al. (2015) Imatinib mesylate for the treatment of steroid-refractory sclerotic-type cutaneous chronic graft-versus-host disease. Biol Blood Marrow Transplant 21:1083-90
Curtis, Lauren M; Datiles 3rd, Manuel B; Steinberg, Seth M et al. (2015) Predictive models for ocular chronic graft-versus-host disease diagnosis and disease activity in transplant clinical practice. Haematologica 100:1228-36

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