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Trial registered on ANZCTR


Registration number
ACTRN12616001066471
Ethics application status
Approved
Date submitted
5/08/2016
Date registered
9/08/2016
Date last updated
29/06/2021
Date data sharing statement initially provided
21/01/2019
Type of registration
Prospectively registered

Titles & IDs
Public title
Do donor white blood cells survive in children who need a blood transfusion?
Scientific title
Is there an incidence of donor white blood cell survival (microchimerism) in paediatric transfusion recipients?
Secondary ID [1] 289857 0
None
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Blood Transfusion related outcomes 299796 0
Microchimerism 299797 0
Condition category
Condition code
Blood 299725 299725 0 0
Other blood disorders

Intervention/exposure
Study type
Observational
Patient registry
False
Target follow-up duration
Target follow-up type
Description of intervention(s) / exposure
This study is a pilot observational study only. A blood sample (1mL, 0.2 teaspoon) will be taken from any paediatric patients with any indication who requires a routine blood transfusion with at least one paediatric sized red blood cell unit as standard of care treatment. Since some patients will require multiple transfusions over the course of their treatment. The research samples will be taken before transfusion and during other routine standard of care samples that will be taken, this can mean samples will be taken every week or every few months depending on the clinical diagnosis of the patient. It is expected that each patient may provided up to, but not limited to, 10 samples over the 18 month study period and up to 12 months post transfusion.
Intervention code [1] 295539 0
Early Detection / Screening
Comparator / control treatment
A comparative group will be found in the retrospective study where patients who were first transfused 5-15 years ago will provide a single (1mL, 0.2 teaspoon) research sample for microchimerism testing. If long-term donor white blood cell survival is found in these patients they can be compared with patients who are currently undergoing blood transfusion. Patients who are current patients are vital to study in addition to the retrospective cohort as transfusion manufacturing processes have changed over time, there is also the introduction of new white blood cell filters which may or may not have an effect on the current incidence of microchimerism and also trying to determine when microchimerism establishes in a patient may be found.
Control group
Active

Outcomes
Primary outcome [1] 299185 0
To determine if donor white blood cells survive in paediatric patients who are transfused with red blood cell units. This will be achieved using a sensitive genetic real time polymerase chain reaction test on specific non-coding DNA sequences. This outcome is relevant for both the retrospective and prospective patient cohort
Timepoint [1] 299185 0
For retrospective participants
a single research sample (1mL, 0.2 teaspoon volume) will be taken, this sample could be between 5-15 years since the commencement of their transfusion treatment.

For prospective participants
Samples will be taken before transfusion (baseline)
and before each red blood cell transfusion is administered at the same time as other routine standard of care testing (these will be patient dependent timepoints with up to but not limited to 10 samples collected over 18 month recruitment period).
Secondary outcome [1] 326447 0
None
Timepoint [1] 326447 0
N/A

Eligibility
Key inclusion criteria
For retrospective study
Male and female paediatric patients between the age of 0-16 years of age admitted for (but not limited to) haematology or oncology conditions which require chronic blood transfusion as part of treatment and who have received at least one blood transfusion between 5-15 years prior to enrollment into this study.

For prospective study
Male and female paediatric patients between the age of 0-16 years of age admitted for (but not limited to) haematology or oncology conditions which require chronic blood transfusion as part of treatment.
Minimum age
No limit
Maximum age
16 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
For both retrospective and prospective studies these exclusion criteria apply:
1)No blood transfusion given
2) Females who are pregnant, or have previously been pregnant
3) Mentally impaired or individuals in dependant relationships who are not sound of mind to consent to agree to participate in this study.

Study design
Purpose
Screening
Duration
Longitudinal
Selection
Defined population
Timing
Both
Statistical methods / analysis
Directed measures outcomes. Patients will either have a positive or negative outcome for the test of microchimerism. The number of patients for recruitment is 200. This recruitment target will be achievable in the timeframe, will give a good indication of whether there is an incidence of microchimerism in this patient population, given that 10% incidence was found in the Australian major trauma study. This number of patients has also been funded where preliminary data could lead to a larger study in the area whereby more health related analyses could be performed.

Recruitment
Recruitment status
Stopped early
Data analysis
Data collected is being analysed
Reason for early stopping/withdrawal
Participant recruitment difficulties
Date of first participant enrolment
Anticipated
5/09/2016
Actual
5/12/2016
Date of last participant enrolment
Anticipated
Actual
31/12/2020
Date of last data collection
Anticipated
Actual
31/12/2020
Sample size
Target
200
Accrual to date
Final
44
Recruitment in Australia
Recruitment state(s)
QLD
Recruitment hospital [1] 6416 0
Lady Cilento Children's Hospital - South Brisbane
Recruitment hospital [2] 6417 0
John Hunter Children's Hospital - New Lambton
Recruitment postcode(s) [1] 13957 0
2305 - New Lambton
Recruitment postcode(s) [2] 13956 0
4101 - South Brisbane

Funding & Sponsors
Funding source category [1] 294234 0
Government body
Name [1] 294234 0
Australian Red Cross Blood Service
Country [1] 294234 0
Australia
Primary sponsor type
Government body
Name
Australian Red Cross Blood Service
Address
Research and Development
17 O'Riordan Street
Alexandria, Sydney NSW 2015
Country
Australia
Secondary sponsor category [1] 293063 0
None
Name [1] 293063 0
Address [1] 293063 0
Country [1] 293063 0
Other collaborator category [1] 279145 0
Hospital
Name [1] 279145 0
Lady Cilento Children's hospital
Address [1] 279145 0
Department of Haematology
501 Stanley St
South Brisbane QLD 4101
Country [1] 279145 0
Australia
Other collaborator category [2] 279146 0
Hospital
Name [2] 279146 0
John Hunter Children's Hospital
Address [2] 279146 0
Department of oncology
Kookaburra Circuit
New Lambton Heights NSW 2305
Country [2] 279146 0
Australia

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 295653 0
Hunter New England Local Health District HREC
Ethics committee address [1] 295653 0
Hunter New England Research Support & Development office
Locked bag 1
New Lambton NSW 2305
Ethics committee country [1] 295653 0
Australia
Date submitted for ethics approval [1] 295653 0
20/04/2016
Approval date [1] 295653 0
02/05/2016
Ethics approval number [1] 295653 0
16/04/20/4.08

Summary
Brief summary
Some adverse transfusion-related reactions are hypothesised to be primarily mediated by donor white blood cells (leucocytes) present in red blood cell (RBC) units. Leucodepletion (removal of leucocytes via filtration) has successfully reduced transfusion related reactions, however current clinical data suggests that RBC transfusion can still result in poor patient outcomes. One such undesirable outcome is the development of microchimerism, where genetically distinct donor leucocytes are detected within a transfused patient. Transfusion-associated microchimerism has primarily been reported in trauma patients who receive multiple blood units and often have an underlying disruption of their immune response. In Australia, we reported that despite the use of leucodepleted blood components 10% of trauma patients showed an incidence of microchimerism. However, it is still unknown whether there is an incidence of microchimerism in other Australian transfusion recipients.
This study aims to gather preliminary data on the incidence of microchimerism in chronically transfused paediatric patients. These patients were chosen since they receive multiple RBC units and may be immunosuppressed at the time of transfusion.
It is currently unknown whether chronic red blood cell treatment results in long term donor white cell survival (microchimerism) within this patient group and whether the use of gamma-irradiated blood components can affect any potential incidence found. To test for the presence of surviving donor cells in chronically transfused paediatric cases both a retrospective (look-back) and prospective (current) study will be collected. For the retrospective study, a single blood samples (1mL) will be analysed for an incidence of microchimerism. These patients will have been transfused 5-15 years ago and will enable data to be gathered on whether there is a long-term donor cell survival. For the prospective study, a blood sample (1mL) will be collected before transfusion, routinely before each red blood cell unit transfusion during the course of their treatment and at 12-18 months following treatment completion. Genomic DNA will be isolated from the blood sample which will undergo a sensitive genetic test for a series of insertion/deletion sequences which are diagnostic for the presence of microchimerism.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 68022 0
Dr Rena Hirani
Address 68022 0
Australian Red Cross Blood Service
Research and Development
17 O'Riordan Street
Alexandria NSW 2015
Country 68022 0
Australia
Phone 68022 0
+61292342454
Fax 68022 0
+61292342411
Email 68022 0
[email protected]
Contact person for public queries
Name 68023 0
Rena Hirani
Address 68023 0
Australian Red Cross Blood Service
Research and Development
17 O'Riordan Street
Alexandria NSW 2015
Country 68023 0
Australia
Phone 68023 0
+61292342454
Fax 68023 0
+61292342411
Email 68023 0
[email protected]
Contact person for scientific queries
Name 68024 0
Rena Hirani
Address 68024 0
Australian Red Cross Blood Service
Research and Development
17 O'Riordan Street
Alexandria NSW 2015
Country 68024 0
Australia
Phone 68024 0
+61292342454
Fax 68024 0
+61292342411
Email 68024 0
[email protected]

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment
Individual data will not be provided as consent for this has not been provided by the participants


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

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