oGVHD After Bone Marrow Transplantation: a Territory-wide Cohort

December 9, 2021 updated by: Allie Lee, The University of Hong Kong

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

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.

Study Overview

Status

Recruiting

Conditions

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.

Study Type

Observational

Enrollment (Anticipated)

500

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

  • Name: Allie Lee
  • Phone Number: +852 39621405
  • Email: aleeni@hku.hk

Study Contact Backup

Study Locations

  • Hong Kong
      • Hong Kong, Hong Kong
        • Recruiting
        • Department of Ophthalmology, LKS Faculty of Medicine, The University of Hong Kong
        • Principal Investigator:
          • Allie Lee

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

Yes

Genders Eligible for Study

All

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.

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

Cohorts and Interventions

Group / Cohort
Post-Haematopoietic Stem Cell Transplantation (Post-HSCT) patients
  • Patient aged 18 or above
  • Underwent allogeneic HSCT in Queen Mary Hospital(QMH) in the two-year recruitment period
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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Population-based epidemiology of oGVHD after allogeneic HSCT
Time Frame: 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)
5 years, starting from the baseline visit

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Longitudinal change in OSDI scores
Time Frame: 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.
5 years, starting from the baseline visit
Serial changes in the anatomy, function & quantity of Meibomian gland
Time Frame: 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.
5 years, starting from the baseline visit
Prevalence of ocular surface disease pre-BMT
Time Frame: 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).
5 years, starting from the baseline visit
Compositional and density changes in ocular surface microbiome over time
Time Frame: 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.
5 years, starting from the baseline visit
Proteomics of tear secretions
Time Frame: 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.
5 years, starting from the baseline visit

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

The University of Hong Kong

Investigators

  • Principal Investigator: Allie Lee, The University of Hong Kong

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

April 30, 2021

Primary Completion (Anticipated)

October 1, 2028

Study Completion (Anticipated)

October 1, 2028

Study Registration Dates

First Submitted

June 11, 2021

First Submitted That Met QC Criteria

December 9, 2021

First Posted (Actual)

December 27, 2021

Study Record Updates

Last Update Posted (Actual)

December 27, 2021

Last Update Submitted That Met QC Criteria

December 9, 2021

Last Verified

December 1, 2021

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • UW 21-145

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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