Help guide our efforts to modernize
Send us your comments by March 14, 2020. Menu

Study on Systemic and Airway Biomarkers in Haemopoietic Stem Cell Transplantation

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT00956358
Recruitment Status : Completed
First Posted : August 11, 2009
Last Update Posted : May 12, 2016
Information provided by (Responsible Party):
James Chung-Man HO, The University of Hong Kong

Brief Summary:

Haemopoietic stem cell transplantation (HSCT) has become a major life-saving treatment for many haematological conditions, mostly malignancies.

However, there are lots of potential complications that hinder the long-term success of HSCT, in which bronchiolitis obliterans syndrome (BOS) is one of such serious complications. Basically, BOS represents a form of graft-versus-host immunological damage of small airways (bronchioles), leading to progressive narrowing of small airways and thus obstructive lung function abnormalities. With progressive loss of lung function in BOS, patients after HSCT can be complicated by intractable respiratory failure that results in mortality. Up until now, there is still no reliable way to accurately predict or detect BOS early to allow pharmacological interventions.

Therefore there is intense interest in the search for biomarkers that can help to predict the occurrence of BOS after HSCT. Apart from biomarkers (e.g., cytokines) in blood, there has been recent development in the sampling of airway lining fluid by a non-invasive method, i.e., collection of exhaled breath condensate (EBC). In airway diseases such as asthma or chronic obstructive pulmonary disease, EBC has been found to have various cytokines which can serve as potential biomarkers of disease activity. Since BOS is largely a small airway disease, it becomes logical to investigate the profile of biomarkers in EBC as predictors for BOS after HSCT.

Therefore this study has been designed to look into the role of biomarkers in blood and EBC in early detection of BOS after HSCT.

Condition or disease
Hematological Diseases

Detailed Description:

Haemopoietic stem cell transplantation (HSCT) has revolutionized the treatment of both haematological and perhaps some solid malignancies. However, despite recent technological advancements, HSCT is still associated with significant mortality and morbidities.

Apart from various infective complications in early stage post-HSCT, bronchiolitis obliterans syndrome (BOS) has been a well-known late complication that can result in high mortality. It has been mostly associated with those who develop chronic graft-versus-host disease after allogeneic HSCT. Clinically, the diagnosis of BOS is largely based on demonstration of obstructive lung function abnormalities and air-trapping in computed tomography scan of thorax. Pathologically, bronchiolitis obliterans is characterized by both inflammatory and fibrotic reactions in the small bronchioles leading to subsequent obliteration. Upon diagnosis of BOS post-HSCT, inhaled corticosteroid (with or without bronchodilators) is commonly prescribed as anti-inflammatory agent, though with undocumented clinical efficacy. Unfortunately, there is still a lack of reliable biomarkers that can predict or allow early detection of BOS, preferably in the early and potentially reversible stage of development of BOS.

Apart from measuring circulating biomarkers in blood, exhaled breath condensate (EBC) has recently emerged as a non-invasive sampling method for real-time analysis and evaluation of oxidative stress biomarkers in the lower respiratory tract airways, especially in various lung diseases including asthma, chronic obstructive pulmonary disease, and lung cancer. As bronchiolitis obliterans is predominantly a disease of the small bronchioles, it is highly likely to be associated with changes in various inflammatory and oxidative stress biomarkers in EBC. However, the role of measuring EBC biomarkers in predicting the occurrence of BOS after HSCT has not been studied. Therefore, the current study aims to evaluate the temporal changes of various oxidative stress biomarkers and cytokines in EBC and blood in patients with haematological conditions who undergo allogeneic HSCT, with regard to the subsequent development of BOS.

Layout table for study information
Study Type : Observational
Actual Enrollment : 228 participants
Observational Model: Case Control
Time Perspective: Prospective
Official Title: Study on Systemic and Airway Cytokines and Oxidative Stress in Patients Undergoing Haemopoietic Stem Cell Transplantation (HSCT)
Study Start Date : March 2009
Actual Primary Completion Date : December 2015
Actual Study Completion Date : December 2015

Resource links provided by the National Library of Medicine

Haematological conditions requiring haemopoietic stem cell transplantation
Post-HSCT with BOS
Occurence of bronchiolitis obliterans syndrome after haemopoietic stem cell transplantation
Healthy HSCT donors

Primary Outcome Measures :
  1. Lung function indices [ Time Frame: Every 3 months until either 18 months post-HSCT or diagnosis of BOS ]

Biospecimen Retention:   Samples Without DNA
Plasma, buffy coat, red blood cell and exhaled breath condensate samples.

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.

Layout table for eligibility information
Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Sampling Method:   Non-Probability Sample
Study Population
Haematological conditions requiring HSCT and healthy HSCT donors will be identified from Bone Marrow Transplatation (BMT) Unit and post-HSCT patients with BOS will be identified from Respiratory Medicine clinics at Queen Mary Hospital.

Inclusion Criteria:

  • Haematological conditions requiring HSCT (either autologous or allogeneic with sibling donor), post-HSCT BOS, or healthy HSCT donors
  • Life expectancy > 12 weeks

Exclusion Criteria:

  • Respiratory failure requiring use of supplemental oxygen therapy
  • Known airway diseases including asthma, chronic obstructive pulmonary disease and bronchiectasis

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT00956358

Layout table for location information
Hong Kong
Queen Mary Hospital
Hong Kong, Hong Kong
Sponsors and Collaborators
The University of Hong Kong
Layout table for investigator information
Principal Investigator: Chung-man James Ho The University of Hong Kong

Layout table for additonal information
Responsible Party: James Chung-Man HO, Clinical Assistant Professor, The University of Hong Kong Identifier: NCT00956358    
Other Study ID Numbers: UW 09-107
First Posted: August 11, 2009    Key Record Dates
Last Update Posted: May 12, 2016
Last Verified: May 2016
Keywords provided by James Chung-Man HO, The University of Hong Kong:
bronchiolitis obliterans syndrome
Additional relevant MeSH terms:
Layout table for MeSH terms
Hematologic Diseases