title: Predictive models for ocular chronic graft-versus-host disease diagnosis and disease activity in transplant clinical practice.
abstract: Ocular chronic graft-versus-host disease is one of the most bothersome common complications following allogeneic hematopoietic stem cell transplantation. The National Institutes of Health Chronic Graft-versus-Host Disease Consensus Project provided expert recommendations for diagnosis and organ severity scoring. However, ocular chronic graft-versus-host disease can be diagnosed only after examination by an ophthalmologist. There are no currently accepted definitions of ocular chronic graft-versus-host disease activity. The goal of this study was to identify predictive models of diagnosis and activity for use in clinical transplant practice. A total of 210 patients with moderate or severe chronic graft-versus-host disease were enrolled in a prospective, cross-sectional, observational study (clinicaltrials.gov identifier: 00092235). Experienced ophthalmologists determined presence of ocular chronic graft-versus-host disease, diagnosis and activity. Measures gathered by the transplant clinician included Schirmer's tear test and National Institutes of Health 0-3 Eye Score. Patient-reported outcome measures were the ocular subscale of the Lee Chronic Graft-versus-Host Disease Symptom Scale and Chief Eye Symptom Intensity Score. Altogether, 157 (75%) patients were diagnosed with ocular chronic graft-versus-host disease; 133 of 157 patients (85%) had active disease. In a multivariable model, the National Institutes of Health Eye Score (P<0.0001) and Schirmer's tear test (P<0.0001) were independent predictors of ocular chronic graft-versus-host disease (sensitivity 93.0%, specificity 92.2%). The Lee ocular subscale was the strongest predictor of active ocular chronic graft-versus-host disease (P<0.0001) (sensitivity 68.5%, specificity 82.6%). Ophthalmology specialist measures that were most strongly predictive of diagnosis in a multivariate model were Oxford grand total staining (P<0.0001) and meibomian score (P=0.027). These results support the use of selected transplant clinician- and patient-reported outcome measures for ocular chronic graft-versus-host disease screening when providing care to allogeneic hematopoietic stem cell transplantation survivors with moderate to severe chronic graft-versus-host disease. Prospective studies are needed to determine if the Lee ocular subscale demonstrates adequate responsiveness as a disease activity outcome measure.
authors.affiliation: Experimental Transplantation and Immunology Branch, National Cancer institute (NCI), National Institutes of Health (NIH), Bethesda, MD, USA.
authors.forename: Lauren M
authors.initials: LM
authors.lastname: Curtis
authors.affiliation: National Eye Institute, NIH, Bethesda, MD, USA.
authors.forename: Manuel B
authors.initials: MB
authors.lastname: Datiles
authors.affiliation: Biostatistics and Data Management Section, NCI, NIH, Rockville, MD, USA.
authors.forename: Seth M
authors.initials: SM
authors.lastname: Steinberg
authors.affiliation: Outcomes Research Branch, Division of Cancer Control and Population Sciences, NCI, NIH, Rockville, MD, USA.
authors.forename: Sandra A
authors.initials: SA
authors.lastname: Mitchell
authors.affiliation: National Eye Institute, NIH, Bethesda, MD, USA.
authors.forename: Rachel J
authors.initials: RJ
authors.lastname: Bishop
authors.affiliation: Dermatology Branch, NCI, NIH, Bethesda, MD, USA.
authors.forename: Edward W
authors.initials: EW
authors.lastname: Cowen
authors.affiliation: National Institutes of Dental and Craniofacial Research, NIH, Bethesda, MD, USA.
authors.forename: Jacqueline
authors.initials: J
authors.lastname: Mays
authors.affiliation: Bone Marrow Transplant Program, Massey Cancer Center, Virginia Commonwealth University Medical Center, Richmond, VA, USA.
authors.forename: John M
authors.initials: JM
authors.lastname: McCarty
authors.affiliation: Experimental Transplantation and Immunology Branch, National Cancer institute (NCI), National Institutes of Health (NIH), Bethesda, MD, USA.
authors.forename: Zoya
authors.initials: Z
authors.lastname: Kuzmina
authors.affiliation: Experimental Transplantation and Immunology Branch, National Cancer institute (NCI), National Institutes of Health (NIH), Bethesda, MD, USA.
authors.forename: Filip
authors.initials: F
authors.lastname: Pirsl
authors.affiliation: Experimental Transplantation and Immunology Branch, National Cancer institute (NCI), National Institutes of Health (NIH), Bethesda, MD, USA.
authors.forename: Daniel H
authors.initials: DH
authors.lastname: Fowler
authors.affiliation: Experimental Transplantation and Immunology Branch, National Cancer institute (NCI), National Institutes of Health (NIH), Bethesda, MD, USA.
authors.forename: Ronald E
authors.initials: RE
authors.lastname: Gress
authors.affiliation: Experimental Transplantation and Immunology Branch, National Cancer institute (NCI), National Institutes of Health (NIH), Bethesda, MD, USA pavletis@mail.nih.gov.
authors.forename: Steven Z
authors.initials: SZ
authors.lastname: Pavletic
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D064591:Allografts; D002648:Child; D002908:Chronic Disease; D005128:Eye Diseases / Q000175:diagnosis* / Q000209:etiology / Q000473:pathology*; D005260:Female; D006086:Graft vs Host Disease / Q000175:diagnosis* / Q000209:etiology / Q000473:pathology*; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D008297:Male; D008875:Middle Aged; D008954:Models, Biological; D011237:Predictive Value of Tests