Clinical trial NCT05170347: oGVHD After Bone Marrow Transplantation: a Territory-wide Cohort
Official title: Ocular Graft-Versus-Host-Disease After Allogeneic Haematopoietic Stem Cell Transplantation: A Territory-Wide Prospective Cohort
Study type: OBSERVATIONAL
Overall status: RECRUITING
Conditions: Graft Vs Host Disease
Haematological Malignancy
Cancer
Keywords: Graft Vs Host Disease
Bone Marrow Transplant
Cancer
Haematological malignancy
Lead sponsor: The University of Hong Kong
Sponsor class: OTHER
First posted: 2021-12-27
Enrollment: 500
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: PROBABILITY_SAMPLE
Study population: In a two-year recruitment period, all patients attending the pre-HSCT assessment clinic in the Bone Marrow Transplant Centre (BMTC) at Queen Mary Hospital (QMH) will be invited to join the cohort. The sample size is estimated to be 250. This is based on the calculation that, each year, approximately 120-130 patients underwent allogeneic HSCT at the BMTC of QMH.

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Population-based epidemiology of oGVHD after allogeneic HSCT
timeFrame: 5 years, starting from the baseline visit
Secondary outcomes:
measure: Longitudinal change in OSDI scores
timeFrame: 5 years, starting from the baseline visit
measure: Serial changes in the anatomy, function & quantity of Meibomian gland
timeFrame: 5 years, starting from the baseline visit
measure: Prevalence of ocular surface disease pre-BMT
timeFrame: 5 years, starting from the baseline visit
measure: Compositional and density changes in ocular surface microbiome over time
timeFrame: 5 years, starting from the baseline visit
measure: Proteomics of tear secretions
timeFrame: 5 years, starting from the baseline visit
Other outcomes:
Locations:
city: Hong Kong
country: Hong Kong
facility: Department of Ophthalmology, LKS Faculty of Medicine, The University of Hong Kong
Study officials:
affiliation: The University of Hong Kong
name: Allie Lee
role: PRINCIPAL_INVESTIGATOR
References:
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citation: Na KS, Yoo YS, Mok JW, Lee JW, Joo CK. Incidence and risk factors for ocular GVHD after allogeneic hematopoietic stem cell transplantation. Bone Marrow Transplant. 2015 Nov;50(11):1459-64. doi: 10.1038/bmt.2015.187. Epub 2015 Aug 24.
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