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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]

None

Universal Trial Number (UTN)

Trial acronym

Linked study record

Health condition

Health condition(s) or problem(s) studied:

Blood Transfusion related outcomes

Microchimerism

Condition category

Condition code

Blood

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]

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]

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]

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]

None

Timepoint [1]

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?

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

Recruitment in Australia

Recruitment state(s)

QLD

Recruitment hospital [1]

Lady Cilento Children's Hospital - South Brisbane

Recruitment hospital [2]

John Hunter Children's Hospital - New Lambton

Recruitment postcode(s) [1]

4101 - South Brisbane

Recruitment postcode(s) [2]

2305 - New Lambton

Funding & Sponsors

Funding source category [1]

Government body

Name [1]

Australian Red Cross Blood Service

Address [1]

Research and Development
17 O'Riordan Street
Alexandria, Sydney NSW 2015

Country [1]

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]

None

Name [1]

Address [1]

Country [1]

Other collaborator category [1]

Hospital

Name [1]

Lady Cilento Children's hospital

Address [1]

Department of Haematology
501 Stanley St
South Brisbane QLD 4101

Country [1]

Australia

Other collaborator category [2]

Hospital

Name [2]

John Hunter Children's Hospital

Address [2]

Department of oncology
Kookaburra Circuit
New Lambton Heights NSW 2305

Country [2]

Australia

Ethics approval

Ethics application status

Approved

Ethics committee name [1]

Hunter New England Local Health District HREC

Ethics committee address [1]

Hunter New England Research Support & Development office
Locked bag 1
New Lambton NSW 2305

Ethics committee country [1]

Australia

Date submitted for ethics approval [1]

20/04/2016

Approval date [1]

02/05/2016

Ethics approval number [1]

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

Dr Rena Hirani

Address

Australian Red Cross Blood Service
Research and Development
17 O'Riordan Street
Alexandria NSW 2015

Country

Australia

Phone

+61292342454

Fax

+61292342411

[email protected]

Contact person for public queries

Name

Rena Hirani

Address

Australian Red Cross Blood Service
Research and Development
17 O'Riordan Street
Alexandria NSW 2015

Country

Australia

Phone

+61292342454

Fax

+61292342411

[email protected]

Contact person for scientific queries

Name

Rena Hirani

Address

Australian Red Cross Blood Service
Research and Development
17 O'Riordan Street
Alexandria NSW 2015

Country

Australia

Phone

+61292342454

Fax

+61292342411

[email protected]

Data sharing statement

Will individual participant data (IPD) for this trial be available (including data dictionaries)?

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

Documents added manually

No documents have been uploaded by study researchers.

Documents added automatically

No additional documents have been identified.

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