oGVHD After Bone Marrow Transplantation: a Territory-wide Cohort

Recruiting

• Conditions: Graft Vs Host Disease; Cancer; Haematological Malignancy

• Registration Number: NCT05170347
• Lead Sponsor: The University of Hong Kong

Brief Summary

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

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.

Basic Information
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Recruitment & Eligibility
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Study & Design
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Trial Locations

Study Timeline

• Study Start: 2021-04-30
• Study First Submitted: 2021-06-11
• Status Verified: 2021-12
• Study First Submitted QC: 2021-12-09
• Last Update Submitted: 2021-12-09
• Study First Posted: 2021-12-27
• Last Update Posted: 2021-12-27
• Primary Completion: 2028-10
• Study Completion: 2028-10

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 500

Inclusion Criteria

• Patient aged 18 or above
• Underwent allogeneic HSCT in QMH in the two-year recruitment period

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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.

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Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Population-based epidemiology of oGVHD after allogeneic HSCT	5 years, starting from the baseline visit	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)

Secondary Outcome Measures

Name	Time	Method
Longitudinal change in OSDI scores	5 years, starting from the baseline visit	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.
Serial changes in the anatomy, function & quantity of Meibomian gland	5 years, starting from the baseline visit	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.
Prevalence of ocular surface disease pre-BMT	5 years, starting from the baseline visit	(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).
Compositional and density changes in ocular surface microbiome over time	5 years, starting from the baseline visit	Changes in diversity and density of microbial colonies on the ocular surface are hypothesised to be involved in oGVHD pathogenesis, and hence are investigated.
Proteomics of tear secretions	5 years, starting from the baseline visit	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.

Trial Locations

Locations (1)

Department of Ophthalmology, LKS Faculty of Medicine, The University of Hong Kong; 🇭🇰 Hong Kong, Hong Kong