Ocular graft-versus-host disease: Risk factors of ocular graft-versus-host disease after allogeneic haematopoietic stem cell transplantation in Denmark.
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Allogeneic haematopoietic stem cell transplantation (HSCT) is used to cure both malignant and non-malignant haematological diseases. Despite HSCT has been available for more than 50 years, chronic graft-versus-host disease (cGVHD) remains a difficult immunologically mediated challenge, which increases morbidity and mortality after transplantation. When cGVHD targets the eyes, it causes reduced tears and inflammation which lead to red, irritated eyes, corneal damage and blindness in worst cases. Ocular cGVHD significantly reduces quality of life after HSCT. We need to gain further knowledge about this disease to help this patient group. The overall aim of this PhD project was to investigate the incidence and risk factors for developing ocular cGVHD in both adults and children. Furthermore, the objective was to investigate possible associations between ocular cGVHD and cGVHD in other organs, and mortality after HSCT. A conditioning regimen is given to the patient before transplantation, which can be either myeloablative (MA) or non-myeloablative (NMA). Our studies showed that in adults, the 5-year cumulative incidence of ocular cGVHD was 18% after MA and 35% after NMA regimen. Several factors were associated with a higher risk of ocular cGVHD after both conditioning regimens. In the MA group, malignant disease, Schirmer's test ≤10 mm/5 min before HSCT, the use of a matched unrelated donor or female donor, peripheral blood as stem cell source and acute GVHD (grade III-IV) increased the risk of ocular cGVHD. In the NMA group, Schirmer's test ≤10 mm/5 min before transplantation and higher recipient age increased the risk of ocular cGVHD. In children, the incidence of ocular cGVHD was 6% and therefore less common than in adults. Ocular cGVHD was more frequent in patients with extensive cGVHD, and when other ectodermal derived organs were involved (skin, mouth, genitals and nails). The frequency of ocular cGVHD was especially high in patients with skin sclerosis as a manifestation of cGVHD (70%). Our studies suggest that target antigens in ectodermal derived organs might be involved in the complex pathophysiology of ocular cGVHD, but more studies are needed to explore this. Ocular cGVHD was furthermore found to be associated with a higher non-relapse mortality. In conclusion, several risk factors for developing ocular cGVHD exists. This knowledge may be applied to guide clinical trials (i.e. power calculations), to inform patients of their risk of developing ocular cGVHD and to guide clinicians in scheduling patient follow-up. Because of the many patients with signs of dry eyes before HSCT (which increase the risk of ocular cGVHD), we recommend performing a baseline ophthalmological examination before HSCT. More studies are needed to elucidate the pathophysiology of ocular GVHD. In the future, this could lead to better treatment options and potentially prevention of the disease.