Irradiated components

TA-GVHD is a rare but almost universally fatal complication of transfusion.

The primary cause is the proliferation and engraftment of transfused donor T lymphocytes in the bone marrow of susceptible recipients. Irradiation inactivates viable T-lymphocytes in cellular blood components.

Updated ANZSBT Guidelines for Prevention of Transfusion-Associated Graft-Versus-Host Disease (2nd Edition) were released in February 2024 and provide comprehensive guidance.

How are blood products irradiated?

X-ray irradiation (used by Lifeblood) and gamma irradiation are considered equivalent for TA-GVHD prevention.

The minimum dose of irradiation is 25 Gy to all parts of the unit, with no part receiving more than 50 Gy.

Radiosensitive indicator labels are applied to the unit to provide evidence of irradiation.

What blood products does irradiation apply to?

Cellular components including red cells, platelets and granulocytes must be irradiated where there are appropriate indications.

Stem cells, donor T lymphocytes and chimeric antigen receptor T lymphocytes (CAR-T cells) must not be irradiated as this will make them ineffective.

Cryoprecipitate, fresh frozen plasma, and manufactured plasma products do not require irradiation as these do not contain viable T-cells.

When can products be irradiated?

All platelets and buffy coat granulocytes provided by Lifeblood are irradiated before issue. Red cells can be provided irradiated if ordered for specific clinical requirements.

Red cells may be irradiated at any time up to 14 days after collection, and then stored for a further 14 days from the date of irradiation.
Red cells for intrauterine and exchange transfusion should be as fresh as possible (<5 days old) at irradiation and must be used within 24 hours of irradiation.
Platelets can be irradiated at any stage in their shelf life and then stored up to their normal 7-day expiry.
Granulocytes for all recipients should be irradiated as soon as possible after production and transfused with minimal delay. All buffy coat granulocyte components supplied by Lifeblood are irradiated before issue.

Effects of refrigerated storage duration on non-irradiated red cells

Red cells stored for 21 days or more are irradiation equivalent.
Red cells stored for 14 days or more may be considered TA-GVHD safe and used for patients at risk of TA-GVHD when irradiation equivalent red cells are not

Red cells issued under these criteria must be clearly labelled as such.

What are the side effects and hazards?

Ionising irradiation of red cells causes an increase in the level of extracellular potassium. The clinical significance of the potassium load depends on the speed and volume of the transfusion, as well as the age of the blood.

Where patients are at particular risk of hyperkalaemia, transfusion should occur as soon as possible after irradiation.

When should I use irradiated components?

Irradiation of all components would be the ideal preventative strategy for preventing TA-GVHD in susceptible recipients. However for most organisations this is impractical.

The following list provides health professionals with guidance on the use of irradiated cellular blood components. Clinicians are encouraged to use a risk-based assessment when the risk of irradiation is uncertain.

This guidance, which is based on the Australian and New Zealand Society of Blood Transfusion (ANZSBT) Guidelines for the prevention of transfusion-associated graft-versus-host disease (TA-GVHD), may not cover all clinical scenarios or evolving best practice, and may require an alternative approach based on local clinical policies.

Haematology/oncology

Hodgkin lymphoma

Irradiated cellular blood components are recommended during treatment and for an indefinite period following completion of therapy and confirmation of remission.

Cytotoxic therapies for malignant and non-malignant indications

Patients treated with purine analogues (e.g. fludarabine, cladribine, clofarabine, pentostatin) or with bendamustine for malignant and non-malignant indications should receive irradiated cellular blood components during and following treatment.
Patients treated with alemtuzumab (anti-CD52) for haematological neoplasms should receive irradiated cellular blood components during and following treatment.

Allogeneic haematopoietic stem cell transplants (HSCT)

Patients should receive irradiated cellular blood components from the time of conditioning and for a minimum of 12 months post-transplant;
Patients with active GVHD or immunosuppression for GVHD should continue to receive irradiated cellular blood components.

Autologous haematopoietic stem cell transplants (HSCT)

Patients should receive irradiated cellular blood components from the time of initiating conditioning, with this to be reviewed 6 months post-transplant.
Timelines may be personalised based on T cell recovery and longer durations may be required based on other therapies received.

Chimeric antigen receptor T cells (CAR-T therapy)

CAR-T cell recipients should receive irradiated cellular blood components for a period of 6 months following CAR-T cell infusion.
Longer or shorter periods may be applied based on conditioning regimens and cellular targets.

Non-Hodgkin lymphoma

Irradiated cellular blood components are not recommended unless indicated due to the patient’s specific therapies.

Remission induction and consolidation therapy for acute leukaemia and chemotherapy of similar intensity for other malignancies

Irradiated cellular blood components are recommended for patients undergoing chemotherapy equivalent to AML or ALL intensive remission induction and consolidation therapy, to continue for a period of 6 months following intensive therapy.
Irradiated cellular blood components are not required for acute leukaemia when supportive care only or lower intensity chemotherapy is offered.

T cell immunosuppression

Irradiated cellular blood components are not recommended for patients with immunosuppression following sold organ transplant, corticosteroids, m-TOR inhibitors, antimetabolites, and other agents used in the longer-term control of autoimmune disorders.
Individual clinical risk assessment with emerging therapies should be considered, although for most immunosuppressive agents, irradiation would not be mandated.
Risk assessment may include consideration of degree of immunosuppression including the expected depth and duration of T cell lymphopenia and infection risks.

Aplastic anaemia

Cellular blood components should be irradiated during and following treatment with immunosuppressive therapy including anti-thymocyte globulin or similar T lymphocyte depleting therapy (e.g. alemtuzumab).
Use of irradiated cellular blood components should continue until all immunosuppression has been ceased (including ciclosporin).

Neonates and paediatrics

Intrauterine transfusions (IUT)

All cellular blood components for intrauterine transfusion (IUT) should be irradiated.
Red cells for IUT should be fresh as possible (<5 days old) and must be transfused within 24 hours of irradiation.

Neonatal exchange transfusions

Red cells for neonatal exchange transfusion should be irradiated.
Red cells for neonatal exchange transfusion should be fresh as possible (<5 days old) and must be transfused within 24 hours of irradiation.

Neonates and infants with congenital heart disease (CHD) requiring cardiopulmonary bypass (CPB) surgery or extracorporeal life support (ECLS); and those undergoing cardiothoracic surgery.

Consider evaluating neonates and infants undergoing cardiac surgery for an undiagnosed T-cell immunodeficiency, and where this is not possible/feasible consider irradiation of cellular blood components until risk of relevant immunodeficiency has been excluded.
Consider irradiation of red cells in suspected T cell immunodeficiency.
- As a guide a CD4+ T lymphocyte count >400 cells/μL, of which 30% are naive T lymphocytes, largely excludes severe T cell immunodeficiency in which case irradiated red cells are not indicated.
Discussion with a paediatric immunologist is suggested if there are concerns of a possible T lymphocyte immunodeficiency.
If large volumes of irradiated red cells are used for patients undergoing CPB, ECMO and cardiac surgery, transfusion should ideally occur as soon as possible post-irradiation and within 24 hours, to reduce the risk of hyperkalaemia.

Neonatal top-up transfusions

Neonates who have previously received an IUT, must receive irradiated cellular blood components for small volume transfusions.
Term neonates and pre-term (>28 weeks) infants receiving small volume transfusions do not require irradiated cellular blood components.
In extremely pre-term (<28 weeks) and extremely low birthweight (<1000g) infants, the decision for irradiated components should be based on additional factors other than only gestational age and weight.
Irradiated red cells for small volume neonatal transfusion should be fresh as possible (<5 days old) and must be transfused within 48 hours of irradiation.
- If centrifuged, supernatant removed products (including adult leucodepleted red cell units) are used these must be transfused within 14 days of irradiation.

Emergency and large volume transfusions

Emergency transfusions for neonatal resuscitation do not require irradiated cellular blood components, even in neonates otherwise considered at higher risk of TA-GVHD.
If irradiated red cells are used for large volume neonatal transfusion they should be transfused as soon as possible after irradiation, and preferably within 24 hours of irradiation.

Congenital immunodeficiencies in infants and children

If a severe T lymphocyte immunodeficiency disorder is suspected, irradiated cellular blood components should be given while diagnostic testing is undertaken.
Irradiated cellular blood components are recommended for all infants/children with severe congenital T lymphocyte immunodeficiency syndromes having significant qualitative or quantitative T lymphocyte deficiency.
Irradiation of cellular blood components is not indicated for infants or children with temporary defects of T lymphocyte function including following viral infections, acquired T lymphocyte deficiencies, those who are HIV-antibody positive or with acquired immune deficiency syndrome (AIDS).
Irradiation of cellular blood components is not indicated for infants or children with congenital humoral deficiency disorders.

Transfusion

Cellular blood components

Cellular blood components including red cells, platelets and granulocytes must be irradiated where there are appropriate indications

HLA-matched donors

Cellular blood components from HLA-matched (HLA-compatible) donors must be irradiated.
Stem cells, donor T cells, CAR-T cells or other cellular products required to engraft, whether allogeneic or autologous must not be irradiated as they will be rendered ineffective.

Related donors

Related donors have a higher potential for partial HLA similarities with the recipient, therefore cellular blood components from related donors (“directed donations”) must be irradiated.
Directed donations are discouraged.
Stem cells, donor T-cells, CAR-T cells or other cellular products required to engraft, whether allogeneic or autologous must not be irradiated as they will be rendered ineffective.

Radiation exposure / acute radiation injury

Patients requiring transfusion due to radiation injury should receive irradiated cellular blood components.

Immunology

Congenital immunodeficiencies in infants and children

If a severe T lymphocyte immunodeficiency disorder is suspected, irradiated cellular blood components should be given while diagnostic testing is undertaken.
Irradiated cellular blood components are recommended for all infants/children with severe congenital T lymphocyte immunodeficiency syndromes having significant qualitative or quantitative T lymphocyte deficiency.
Irradiation of cellular blood components is not indicated for infants or children with temporary defects of T lymphocyte function including following viral infections, acquired T lymphocyte deficiencies, those who are HIV-antibody positive or with acquired immune deficiency syndrome (AIDS).
Irradiation of cellular blood components is not indicated for infants or children with congenital humoral deficiency disorders.

HIV/AIDS (with no other indications)

Not necessary to transfuse with irradiated cellular components.

Solid organ transplantation

Solid organ transplant (with no other indications)

Immunosuppression following sold organ transplant is not known to be associated with TA-GVHD therefore irradiated cellular blood components are not recommended.
Individual clinical risk assessment with emerging therapies should be considered, although for most immunosuppressive agents, irradiation of cellular blood components would not be mandated.7

Massive transfusion / critical bleeding

Irradiated cellular blood components are not recommended for critical bleeding or trauma.
For patients at risk of TA-GVHD who need emergency transfusion, the use of the shortest expiry (oldest) suitable red cells is acceptable if irradiated (or equivalent) units are not available.
Important: In the event of critical and life-threatening bleeding, transfusion should not delayed if irradiated cellular products cannot be sourced immediately and a delay in transfusion may result in death.