oGVHD After Bone Marrow Transplantation: a Territory-wide Cohort

Study Overview
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Brief Summary
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Allogeneic Haematopoietic stem cell transplantation (HSCT) is an effective treatment for all array of blood or blood-producing organ disorders. Graft-versus-host-disease (GVHD) occurs as a result of an overactive immunological system against normal host tissues. It can happen in the liver, skin, mucosal surface of the eye, gastrointestinal tract, and genitalia. Ocular GVHD occurs in 30-70% of patients after HSCT. It mainly affects the ocular surface, including the conjunctiva and cornea. In severe cases, multiple clinical manifestations can lead to painful non-healing corneal ulcers, secondary infections, and visual loss. oGVHD can be debilitating and severely impact patients' quality of life. However, there are no widely accepted guidelines available for prevention and management. In collaboration with the Department of Haematology of Queen Mary Hospital, the investigators set out to establish a territory-wide cohort of patients receiving HSCT. Primarily, the investigators aim to establish the population-based epidemiology of oGVHD and understand the natural history and the long-term ophthalmic outcomes of oGVHD via this study.

Detailed Description
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Allogeneic haematopoietic stem cell transplantation (HSCT) is an effective treatment for all array of haematological disorders. Graft-versus-host-disease (GVHD) occurs as a result of an overactive systemic immunological response against normal host tissues, in particular the liver, skin, mucosal surface of the eye, gastrointestinal tract, and genitalia. Ocular graft-versus-host-disease (oGVHD) occurs in 30-70% patients after allogeneic HSCT. It mainly affects the ocular surface, and pathologically it is characterized by decreased conjunctival goblet cell density, increased conjunctival squamous metaplasia, and infiltration of tissues with inflammatory cells. Common clinical manifestations include keratoconjunctivitis sicca, marginal keratitis, conjunctivitis, and conjunctival scarring, and anterior uveitis. In severe cases, these can lead to painful non-healing corneal ulcers, secondary infections, and visual loss. Risk factors for oGVHD reported in the literature included non- Caucasian race, male recipient from female donor, more extensive and severe systemic involvement, pre-existing diabetes mellitus, and use of anti-thymocyte globulin. oGVHD can be debilitating and severely impact patients' quality of life. Although common and significant, currently there are no widely accepted guidelines available for prophylaxis and management. The Haemopoietic Stem Cell Transplantation Centre at Queen Mary Hospital is the only quaternary referral centre for adults in Hong Kong since 1990 and now it serves over 100 patients per year. In collaboration with the Department of Haematology of QMH, the investigators set out to establish a territory-wide cohort of patients receiving allogeneic HSCT to fill the current knowledge gaps.

Official Title
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Ocular Graft-Versus-Host-Disease After Allogeneic Haematopoietic Stem Cell Transplantation: A Territory-Wide Prospective Cohort

Conditions
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Graft Vs Host Disease, Haematological Malignancy, Cancer

Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patient aged 18 or above Underwent allogeneic HSCT in QMH in the two-year recruitment period Exclusion Criteria: Underwent autologous HSCT Patient unable to attend follow-up visits Family Control Subjects The research team will invite an accompanying family member to be the family control. Microbiome and tear samples will be collected for comparison. The sample collection schedule is the same as the corresponding post-HSCT case.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Post-Haematopoietic Stem Cell Transplantation (Post-HSCT) patients<br>Patient aged 18 or above Underwent allogeneic HSCT in Queen Mary Hospital(QMH) in the two-year recruitment period | |
| Family Control Subjects<br>The research team will invite an accompanying family member to be the family control. Microbiome and tear samples will be collected for comparison. The sample collection schedule is the same as the corresponding post-HSCT case. | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Population-based epidemiology of oGVHD after allogeneic HSCT | Incidence of oGVHD at 3 months, 6 months, 9 months, 12 months, 18 months, 24 months, 36 months, 48 months, and 60 months following allogeneic HSCT (according to ? criteria) | 5 years, starting from the baseline visit | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Longitudinal change in OSDI scores | Change in OSDI scores post-BMT over the 5-year study period will be evaluated. OSDI scores are calculated from a Chinese-validated OSDI questionnaire. They assess oGVHD-induced dry eye disease symptom severity and their burden on the patients' quality of life. | 5 years, starting from the baseline visit | 
| Serial changes in the anatomy, function & quantity of Meibomian gland | Since Meibomian gland dysfunction is one of the main clinical features of oGVHD, anatomical, functional and quantitative changes of Meibomian gland will be examined. Parameters associated with Meibomian gland anatomy and quantity include its level of obstruction and dropout, which can be observed from Meibographs taken with the Keratography 5M and LipiView devices. With the help of the ImageJ software, these parameters will be graded according to the () criteria. Degree of Meibomian gland atrophy indicates the functionality of the Meibomian gland thus the degree of Meibomian gland dysfunction. | 5 years, starting from the baseline visit | 
| Prevalence of ocular surface disease pre-BMT | (Purpose). The presence of ocular surface disease will be confirmed through a comprehensive eye examination (visual acuity, intraocular pressure, slit-lamp and fundus examination), Pentacam, specular microscopy (corneal cell density), and tear assessment (tear breakup time (TBUT), fluorescein staining pattern, non-anaesthetic Schirmer's test). | 5 years, starting from the baseline visit | 
| Compositional and density changes in ocular surface microbiome over time | Changes in diversity and density of microbial colonies on the ocular surface are hypothesised to be involved in oGVHD pathogenesis, and hence are investigated. | 5 years, starting from the baseline visit | 
| Proteomics of tear secretions | oGVHD is an ocular complication arisen from the infiltration of inflammatory cells. The presence, type and quantity of inflammatory markers implied in oGVHD pathogenesis will be confirmed through proteomic analysis. Tear matrix metalloproteinase-9 (MMP-9) will be the main inflammatory marker investigated. | 5 years, starting from the baseline visit | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Graft Vs Host Disease, Bone Marrow Transplant, Cancer, Haematological malignancy