title: Sclerotic-type chronic GVHD of the skin: clinical risk factors, laboratory markers, and burden of disease.
abstract: Chronic GVHD is one of the most severe complications of allogeneic HSCT. The sclerotic skin manifestations of cGVHD (ScGVHD) result from inflammation and fibrosis of the dermis, subcutaneous tissue, or fascia, leading to significant functional disability. Risk factors and clinical markers associated with ScGVHD remain largely unexamined. By using a single-visit, cross-sectional design, we evaluated 206 patients with cGVHD at the National Institutes of Health. Most patients manifested severe (ie, 63% National Institutes of Health score "severe"), refractory disease (median treatments = 4). ScGVHD was detected in 109 (52.9%) patients. ScGVHD was associated with greater platelet count (P < .001) and C3 (P < .001), and decreased forced vital capacity (P = .013). Total body irradiation (TBI) was associated with development of ScGVHD (P = .002). TBI administered in reduced-intensity conditioning was most strongly associated with ScGVHD (14/15 patients, P < .0001). Patients with ScGVHD had significant impairments of joint range of motion and grip strength (P < .001). Greater body surface area involvement was associated with poorer survival (P = .015). We conclude that TBI, particularly in reduced-intensity regimens, may be an important risk factor for ScGVHD. Widespread skin involvement is associated with significant functional impairment, distressing symptoms, and diminished survival. This trial is registered at http://www.clinicaltrials.gov as NCT00331968.
authors.affiliation: Dermatology Branch, Center for Cancer Research, National Cancer Institute, Bethesda, MD, USA.
authors.forename: Kathryn J
authors.initials: KJ
authors.lastname: Martires
authors.forename: Kristin
authors.initials: K
authors.lastname: Baird
authors.forename: Seth M
authors.initials: SM
authors.lastname: Steinberg
authors.forename: Lana
authors.initials: L
authors.lastname: Grkovic
authors.forename: Galen O
authors.initials: GO
authors.lastname: Joe
authors.forename: Kirsten M
authors.initials: KM
authors.lastname: Williams
authors.forename: Sandra A
authors.initials: SA
authors.lastname: Mitchell
authors.forename: Manuel
authors.initials: M
authors.lastname: Datiles
authors.forename: Fran T
authors.initials: FT
authors.lastname: Hakim
authors.forename: Steven Z
authors.initials: SZ
authors.lastname: Pavletic
authors.forename: Edward W
authors.initials: EW
authors.lastname: Cowen
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D015415:Biomarkers / Q000097:blood; D002648:Child; D002675:Child, Preschool; D003176:Complement C3 / Q000378:metabolism; D003430:Cross-Sectional Studies; D018572:Disease-Free Survival; D005260:Female; D006086:Graft vs Host Disease / Q000097:blood / Q000401:mortality / Q000473:pathology / Q000503:physiopathology; D019337:Hematologic Neoplasms / Q000097:blood / Q000401:mortality / Q000473:pathology / Q000503:physiopathology / Q000628:therapy; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D008297:Male; D008875:Middle Aged; D010976:Platelet Count; D012307:Risk Factors; D012871:Skin Diseases / Q000097:blood / Q000401:mortality / Q000473:pathology / Q000503:physiopathology; D015996:Survival Rate; D019172:Transplantation Conditioning; D014184:Transplantation, Homologous; D015599:Trauma Severity Indices; D014916:Whole-Body Irradiation
chemical_list: D015415:Biomarkers; D003176:Complement C3