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