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Ocular graft-versus-host disease and dry eye disease after paediatric haematopoietic stem cell transplantation - incidence and risk factors

Bone Marrow Transplantation volume 57, pages 487–498 (2022)Cite this article

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Abstract

Ocular graft-versus-host disease (oGVHD) contributes substantially to morbidity after allogeneic haematopoietic stem cell transplantation (HSCT) but is sparsely investigated in children. We assessed incidence and risk factors for oGVHD and dry eye disease (DED) in a nationwide, single-centre study of 484 consecutive children receiving HSCT during the period 1980–2016. Ophthalmological examinations were performed before and annually at least until five years after HSCT. Twenty-five patients had DED before transplantation (5.6%). The cumulative incidence was 1.9% for acute oGVHD, 6.0% for chronic oGVHD, 8.7% for new onset DED, and 12.7% for new onset Corneal Fluorescein Staining (CFS). In adjusted Fine-Gray regression models, the use of Busulfan was a risk factor for developing acute oGVHD (HR 5.01, p = 0.03), and malignant disease was a risk factor for developing CFS (HR 2.00, p = 0.047). Younger recipient age was associated with reduced risk of DED when comparing children aged 0–4 years with 10–16 years (HR 0.33, p = 0.03). These data underscore the need of attention to DED and oGVHD in relation to HSCT leading to our recommendation of performing ophthalmic examinations in all children before HSCT, and after HSCT when needed, in order to secure diagnosis and treatment of these complications.

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Fig. 1: Flow chart showing the inclusion and exclusion criteria for the patients in the present study.
Fig. 2: Incidence of ocular disease after HSCT and overall survival.

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Acknowledgements

We would like to thank the following foundation for financial support to this study: The Danish Cancer Society (grant R108-A7021-14-S31), Fight for Sight Denmark, Synoptik-Fonden, Dansk Kræftforskningsfond (Danish Cancer Research Fund) and Børnecancerfonden (The Danish Childhood Cancer Foundation).

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Authors and Affiliations

  1. Department of Ophthalmology, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark

    Helene Jeppesen & Steffen Heegaard

  2. Department of Paediatrics and Adolescent Medicine, Copenhagen University Hospital Rigshospitalet, Copenhagen, Denmark

    Katrine Kielsen & Klaus Müller

  3. The Research Unit of General Practice and Section of General Practice, Department of Public Health, University of Copenhagen, Copenhagen, Denmark

    Volkert Siersma

  4. Copenhagen Eye Infirmary, Copenhagen, Denmark

    Jens Lindegaard

  5. Department of Ophthalmology, Mølholm Private Hospital, Vejle, Denmark

    Hanne Olsen Julian

  6. Department of Pathology, Eye Pathology Section, University of Copenhagen, Copenhagen, Denmark

    Steffen Heegaard

  7. Department of Haematology, The Bone Marrow Transplantation Unit, Rigshospitalet, Copenhagen, Denmark

    Henrik Sengeløv

  8. Institute of Clinical Medicine, University of Copenhagen, Rigshospitalet, Copenhagen, Denmark

    Klaus Müller

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  1. Helene Jeppesen
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Contributions

HJ, KK, JL, HOJ, SH, HS and KM participated in planning the study. HJ collected the data. VS performed the incidence and risk analyses and HJ contributed to analysing the data. HJ, KK and KM drafted the manuscript, and all authors revised the manuscript.

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Correspondence to Helene Jeppesen.

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Jeppesen, H., Kielsen, K., Siersma, V. et al. Ocular graft-versus-host disease and dry eye disease after paediatric haematopoietic stem cell transplantation - incidence and risk factors. Bone Marrow Transplant 57, 487–498 (2022). https://doi.org/10.1038/s41409-022-01564-2

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