Irradiated Blood Products (bsh 2020)

 

transfusion-associated gvhd (TA-GVHD)

 

Very rare, but usually fatal, complication occurring after transfusion of lymphocyte-containing blood components.

Risk associated with an individual transfusion episode depends on:

  • Degree of HLA mismatch between donor and recipient is the strongest risk factor

    • E.g. Risk is 10-20x higher in Japanese due to restricted haplotype diversity

  • Number and viability of lymphocytes

    • e.g. more cases reported with ‘fresher’ red cells, none in units stored >14 days

    • e.g. leukocyte depletion has reduced, but not eliminated, cases

  • Immune status of recipient

    • Probably less significant than previously thought

Clinical Features

  • Skin, gut, liver as per other causes of GVHD

  • Severe marrow hypoplasia

  • Median onset 10 days after transfusion

Diagnosis

  • Biopsy of affected organ

  • Presence of donor cells demonstrated by PCR (or rapid turnaround possible with FISH in sex-mismatched cases)

14 cases recorded by SHOT 1996 – 2019

  • Universal Leukodepletion (LD) appears to have reduced, but not eliminated, risk of TA-GVHD

  • Only 1 of the 14 cases occurred since introduction of LD – neonate transfused with maternal blood (not leukodepleted) without irradiation in 2012, died TA-GVHD

  • >1400 reported cases of omission of irradiation where it would normally have been indicated. No TA-GCHD in these patients.

 

Irradiation of blood components

 

Gamma or X-irradiation, minimum dose 25Gy – maximum 50Gy

Not necessary to irradiate FFP, cryoprecipitate, fractionated plasma products or frozen red cells

Red Cells:

  • Irradiate any time up to 14 days post collection

  • Can be stored for 14 days post-irradiation

  • Use within 24 hours if pt at risk of hyperkalaemia (IUT / neonatal)

Platelets

  • Irradiate at any stage during storage and store up to their normal shelf-life form collection date.

  • All HLA-selected components should be irradiated regardless of patient’s immune function

  • Irradiation may be universal (e.g. Scotland and Wales) or on request (e.g. England).

Granulocytes

  • All granulocyte units are irradiated before issue

?alternatives to irradiation?

Leukocyte Depletion

  • All UK cellular products, except granulocytes, are leukodepleted.

  • Specification: >99% of components should contain <5x10e6 leukocytes per unit and >90% of components should contain <1x10e6 leukocytes per unit. This is based on sampling of approx. 1% of all units produced.

  • Internationally, LD units have been implicated in 17% of cases of TA-GVHD

Pathogen Inactivation

  • Available for platelets in some European countries and some centres have stopped irradiating their platelets on this basis. Not currently in use in UK.

Indications for Irradiation, for ALL:

 

  • Donations from first or second-degree relatives, even if pt is immunocompetent

  • HLA-selected components, even if pt is immunocompetent

  • Granulocyte components

  • Intra-uterine transfusion

  • Transfusion where there has been previous IUT, until 6 months post EDD

  • Neonatal exchange transfusions

  • Severe congenital T lymphocyte immunodeficiency syndromes

  • Recipients of Allografts, from the time of starting conditioning chemotherapy until minimum of 6 months post. Continue indefinitely if chronic GVHD or ongoing immunosuppressant use

  • Stem cell donors (including autologous) for 7 days prior to, and during, harvest

  • Autograft patients, from time of starting conditioning until 3 months post-transplant (6 months if TBI used)

  • Hodgkin Lymphoma for life

  • Purine analogue (Fludarabine, cladribine, pentostatin and bendamustine) recipients for life

  • Alemtuzumab recipients with a haematological diagnosis for life

  • ATG recipients for undefined length of time

  • CAR-T Cell recipients for 7 days prior to harvest, and continue until 3 months post infusion.

 

When to report to SHOT

 

All cases of TA-GVHD

Any non-irradiated products transfused to high risk patients

 

Ensuring irradiated requirements are met:

 

Patient education

Patient alert card

Laboratory Flags

Checking of specific requirements as part of bedside check prior to administration of blood components

IT links between pharmacy and laboratory