Risk Factors for Ocular Involvement in Pediatric Graft-Versus-Host Disease.
Adolescent
Bone Marrow Diseases
/ diagnosis
Child
Child, Preschool
Chronic Disease
Eye Diseases
/ diagnosis
Female
Follow-Up Studies
Graft vs Host Disease
/ diagnosis
Hematopoietic Stem Cell Transplantation
/ adverse effects
Humans
Infant
Intestinal Diseases
/ diagnosis
Leukemia, Myeloid, Acute
/ therapy
Liver Diseases
/ diagnosis
Lung Diseases
/ diagnosis
Male
Multivariate Analysis
Precursor Cell Lymphoblastic Leukemia-Lymphoma
/ therapy
Proportional Hazards Models
Retrospective Studies
Risk Factors
Skin Diseases
/ diagnosis
Journal
Cornea
ISSN: 1536-4798
Titre abrégé: Cornea
Pays: United States
ID NLM: 8216186
Informations de publication
Date de publication:
01 Sep 2021
01 Sep 2021
Historique:
received:
14
07
2020
accepted:
27
11
2020
pubmed:
21
1
2021
medline:
15
12
2021
entrez:
20
1
2021
Statut:
ppublish
Résumé
To identify risk factors for ocular graft-versus-host disease (oGVHD) in children with graft-versus-host disease (GVHD). This retrospective cohort study identified 38 children diagnosed with GVHD who underwent an ophthalmological examination. Survival to onset of oGVHD after transplant was analyzed using Kaplan-Meier analyses with log-rank tests. A multivariable Cox proportional hazards model was run for time to oGVHD using univariate risk factors. The average age was 10.0 ± 5.4 years at the time of transplant. Underlying illness was acute lymphoblastic leukemia in 19 (50%) and acute myeloid leukemia in 8 (21%). Nonocular GVHD organ involvement included skin (84%), lungs (16%), intestines (50%), liver (24%), and bone marrow (3%). Fifteen children (39%) had oGVHD, of which 47% were asymptomatic. oGVHD was diagnosed 601 ± 878 days after GVHD. A significant association between risk of oGVHD and diagnosis of acute lymphoblastic leukemia (P = 0.10) or acute myeloid leukemia (P = 0.08) was not found. Organ involvement associated with oGVHD included skin (P = 0.03) and lungs (P = 0.02). Survival curves were significantly influenced by GVHD organ involvement (P = 0.02), but not underlying disease (P = 0.51). The adjusted Cox regression model yielded an independent hazard ratio of 8.82 (95% CI: 1.51-51.49; P = 0.016) for the presence of concomitant GVHD involvement of skin, lungs, and another organ. Children with multiorgan GVHD involvement including skin and lung disease are at increased risk for oGVHD. Given the proportion of asymptomatic cases found in this series, regular eye examinations are warranted in this population.
Identifiants
pubmed: 33470680
doi: 10.1097/ICO.0000000000002659
pii: 00003226-202109000-00016
doi:
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
1158-1164Informations de copyright
Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.
Déclaration de conflit d'intérêts
M. -C. Robert is an employee of EBSCO Health and a consultant for TALLC, Santen, Allergan, and Johnson & Johnson. The remaining authors have no funding or conflicts of interest to disclose.
Références
Nassereddine S, Rafei H, Elbahesh E, et al. Acute graft versus host disease: a comprehensive review. Anticancer Res. 2017;37:1547–1555.
Lee SJ, Vogelsang G, Flowers ME. Chronic graft-versus-host disease. Biol Blood Marrow Transpl. 2003;9:215–233.
Kim SK. Update on ocular graft versus host disease. Curr Opin Ophthalmol. 2006;17:344–348, d8.
Espana EM, Shah S, Santhiago MR, et al. Graft versus host disease: clinical evaluation, diagnosis and management. Graefes Arch Clin Exp Ophthalmol. 2013;251:1257–1266.
Filipovich AH, Weisdorf D, Pavletic S, et al. National Institutes of Health Consensus Development Project on criteria for clinical trials in chronic graft-versus-host disease: I. Diagnosis and Staging Working Group report. Biol Blood Marrow Transplant. 2005;11:945–956.
Jagasia MH, Greinix HT, Arora M, et al. 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 Transpl. 2015;21:389–401.e1.
Jacobs R, Tran U, Chen H, et al. Prevalence and risk factors associated with development of ocular GVHD defined by NIH consensus criteria. Bone Marrow Transpl. 2012;47:1470–1473.
Wang JCC, Teichman JC, Mustafa M, et al. Risk factors for the development of ocular graft-versus-host disease (GVHD) dry eye syndrome in patients with chronic GVHD. Br J Ophthalmol. 2015;99:1514–1518.
Suh DW, Ruttum MS, Stuckenschneider BJ, et al. Ocular findings after bone marrow transplantation in a pediatric population. Ophthalmology. 1999;106:1564–1570.
Bradfield YS, Kushner BJ, Gangnon RE. Ocular complications after organ and bone marrow transplantation in children. J AAPOS. 2005;9:426–432.
Kinori M, Bielorai B, Souroujon D, et al. Ocular complications in children after hematopoietic stem cell transplantation without total body irradiation. Graefes Arch Clin Exp Ophthalmol. 2015;253:1397–1402.
Fahnehjelm KT, Törnquist A-L, Winiarski J. Dry-eye syndrome after allogeneic stem-cell transplantation in children. Acta Ophthalmologica. 2007;86:253–258.
Kalinina Ayuso V, Hettinga Y, van der Does P, et al. Ocular complications in children within 1 year after hematopoietic stem cell transplantation. JAMA Ophthalmol. 2013;131:470–475.
Ng JSK, Lam DSC, Li CK, et al. Ocular complications of pediatric bone marrow transplantation. Ophthalmology. 1999;106:160–164.
Cuvelier GDE, Nemecek ER, Wahlstrom JT, et al. Benefits and challenges with diagnosing chronic and late acute GVHD in children using the NIH consensus criteria. Blood. 2019;134:304–316.
Westeneng AC, Hettinga Y, Lokhorst H, et al. Ocular graft-versus-host disease after allogeneic stem cell transplantation. Cornea. 2010;29:758–763.
Khan R, Nair S, Seth T, et al. Ocular graft versus host disease in allogenic haematopoetic stem cell transplantation in a tertiary care centre in India. Indian J Med Res. 2015;142:543–548.
Pathak M, Diep PP, Lai X, et al. Ocular findings and ocular graft-versus-host disease after allogeneic stem cell transplantation without total body irradiation. Bone Marrow Transpl. 2018;53:863–872.
Hoehn ME, Vestal R, Calderwood J, et al. Ocular complications in school-age children and adolescents after allogeneic bone marrow transplantation. Am J Ophthalmol. 2020;213:153–160.
Vittinghoff E, McCulloch CE. Relaxing the rule of ten events per variable in logistic and Cox regression. Am J Epidemiol. 2007;165:710–718.
Na KS, Yoo YS, Mok JW, et al. Incidence and risk factors for ocular GVHD after allogeneic hematopoietic stem cell transplantation. Bone Marrow Transpl. 2015;50:1459–1464.
Ogawa Y, Shimmura S, Kawakita T, et al. Epithelial mesenchymal transition in human ocular chronic graft-versus-host disease. Am J Pathol. 2009;175:2372–2381.
Ogawa Y, Shimmura S, Dogru M, et al. Immune processes and pathogenic fibrosis in ocular chronic graft-versus-host disease and clinical manifestations after allogeneic hematopoietic stem cell transplantation. Cornea. 2010;29(suppl 1):S68.
Wu M, Liu C, Zhao K, et al. The role of epithelial to mesenchymal transition in the remodeling of lung injury induced by acute graft-versus-host disease. Blood. 2013;122:3257.
Verleden SE, Sacreas A, Vos R, et al. Advances in understanding bronchiolitis obliterans after lung transplantation. Chest. 2016;150:219–225.
Shroff A, Mamalis A, Jagdeo J. Oxidative stress and skin fibrosis. Curr Pathobiol Rep. 2014;2:257–267.
Matsukuma KE, Wei D, Sun K, et al. Diagnosis and differential diagnosis of hepatic graft versus host disease (GVHD). J Gastrointest Oncol. 2016;7:S21–S31.
Hoehn ME, Calderwood J, Gannon E, et al. Ocular complications in a young pediatric population following bone marrow transplantation. J AAPOS. 2018;22:102-106.e1.
Vogelsang GB. How I treat chronic graft-versus-host disease. Blood. 2001;97:1196–1201.
Shikari H, Amparo F, Saboo U, et al. Onset of ocular graft-versus-host disease symptoms after allogeneic hematopoietic stem cell transplantation. Cornea. 2015;34:243–247.