193
PROFESSIONAL ARTICLE
Transfusion associated graft vs. host disease and how to prevent it
1 Blood Transfusion Centre 
of Slovenia, Ljubljana, 
Slovenia
2 Department of 
Heamatology, University 
Medical Centre Ljubljana, 
Ljubljana, Slovenia
3 Department of Internal 
Medicine, Faculty of 
Medicine, University of 
Ljubljana, Ljubljana, 
Slovenia
Correspondence/
Korespondenca:
Aleksandra Barbarić 
Kovačić, e: aleksandra.
barbaric@ztm.si
Key words:
TA-GvHD; blood 
components; irradiation; 
pathogen inactivation
Ključne besede:
TA-GvHD; krvni pripravki; 
obsevanje z ionizirajočimi 
žarki; patogensko 
inaktiviranje
Received: 21. 11. 2019
Accepted: 31. 12. 2020
eng slo element
en article-lang
10.6016/ZdravVestn.3009 doi
21.11.2019 date-received
31.12.2020 date-accepted
Immunology, serology, transplantation Imunologija, selorologija, transplantacija discipline
Professional article Strokovni članek article-type
Transfusion associated graft vs. host disease 
and how to prevent it
Reakcija presadka proti gostitelju po transfuziji 
krvi in kako jo preprečimo
article-title
Transfusion associated graft vs. host disease 
and how to prevent it
Reakcija presadka proti gostitelju po transfuziji 
krvi in kako jo preprečimo
alt-title
TA-GvHD, blood components, irradiation, 
pathogen inactivation
TA-GvHD, krvni pripravki, obsevanje z ionizira-
jočimi žarki, patogensko inaktiviranje
kwd-group
The authors declare that there are no conflicts 
of interest present.
Avtorji so izjavili, da ne obstajajo nobeni 
konkurenčni interesi. conflict
year volume first month last month first page last page
2021 90 3 4 193 201
name surname aff email
Aleksandra Barbarić Kovačić 1 aleksandra.barbaric@ztm.si
name surname aff
Slavica Stanišić 1
Samo Zver 2,3
eng slo aff-id
Blood Transfusion Centre of 
Slovenia, Ljubljana, Slovenia
Zavod RS za transfuzijsko 
medicino, Ljubljana, Slovenija 1
Department of Heamatology, 
University Medical Centre 
Ljubljana, Ljubljana, Slovenia 
Klinični oddelek za hematologijo, 
Univerzitetni klinični center 
Ljubljana, Ljubljana, Slovenija
2
Department of Internal 
Medicine, Faculty of Medicine, 
University of Ljubljana, 
Ljubljana, Slovenia
Katedra za interno medicino, 
Medicinska fakulteta, Univerza v 
Ljubljani, Ljubljana, Slovenija
3
Transfusion associated graft vs. host disease 
and how to prevent it
Reakcija presadka proti gostitelju po transfuziji krvi in kako jo 
preprečimo
Aleksandra Barbarić Kovačić,1 Slavica Stanišić,1 Samo Zver2,3
Abstract
Transfusion associated graft versus host disease (TA-GvHD) is a rare but fatal complication of 
blood components transfusion therapy and has over 90% mortality rate. Transfused donor T 
lymphocytes react against the recipient’s cellular and tissue antigens. Interaction triggers lym-
phocyte activation and, consequently, destruction of target cells in the recipient’s tissues . The 
reason that immune cells of the recipient do not respond appropriately is an incompetent re-
cipient’s immune system and immunodeficiency of the host. Exceptionally, HLA compatibility 
between the donor and the recipient may cause the same reaction.
Most effective way to prevent TA-GvHD is irradiation of the blood components with ionizing ra-
diation. UVA psoralen based pathogen inactivation is an equally effective preventive measure 
of TA-GvHD, but it is applicable only to platelets. For this reason, it is important that physicians 
identify patients at risk of developing TA-GvHD and consequentially always prescribe irradiat-
ed blood units. Blood units that need to be irradiated are erythrocytes and granulocytes, with 
the mentioned exception of platelets. Fresh frozen plasma, cryoprecipitate, blood derived med-
icines, such as albumins, immunoglobulins, blood clotting factors, and erythrocytes after thaw-
ing are not irradiated. The recommended central field irradiation dose is 25-50 Gy.
Izvleček
S transfuzijo povezana reakcija presadka proti gostitelju (angl. Transfusion associated graft 
versus host disease, TA-GvHD) je redek, vendar resen in življenje ogrožajoč zaplet po transfuziji 
krvnih pripravkov. Posledica, kolikor do nje pride, je bolnikova smrt v več kot 90 % primerov. 
Po transfuziji krvi se osebi z imunsko pomanjkljivostjo limfociti T iz darovalčeve krvi odzovejo 
na celične in tkivne antigene prejemnika krvi. Zato darovalčevi limfociti T aktivirajo in uničijo 
tarčne celice v tkivih prejemnika. Vzrok, da se imunske celice prejemnika ne odzovejo tako, da 
bi onemogočile darovalčeve limfocite T, je pomanjkljivost imunskega odziva pri prejemniku in le 
izjemoma vprašanje skladnosti HLA med prejemnikom in darovalcem.
Obsevanje krvnih pripravkov z ionizirajočimi žarki je najbolj učinkovita metoda za preprečevanje 
TA-GvHD. Patogensko inaktiviranje s psoralenom in UVA-žarki je enakovredno obsevanju, ven-
dar se zaenkrat uporablja samo za trombocitne pripravke. Zato je pomembno, da lečeči zdrav-
nik prepozna bolnike, pri katerih lahko nastane TA-GvHD in za njih naroča zgolj obsevane krvne 
pripravke. Obsevamo eritrocite, granulocite ter trombocite, kadar niso patogensko inaktivirani. 
Sveže zmrznjene plazme, krioprecipitata, zdravil iz krvi, kot so albumin, imunoglobulini, faktorji 
strjevanja krvi ... ter eritrocitov po odmrzovanju ne obsevamo, ker je vsebnost limfocitov T zane-
marljiva. Priporočen osrednji obsevalni odmerek je znotraj 25–50 Gy.
Slovenian
Medical
Journal
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1 Introduction
Transfusion-associated graft-versus-
host disease (TA-GvHD) is an exception-
ally rare but serious complication of the 
transfusion of various blood components. 
It mostly appears in immunodeficient 
patients and only exceptionally in the 
immunocompetent.
When an immunocompetent person 
receives a blood transfusion, the donor 
T lymphocytes are only detectable in the 
recipient’s bloodstream for a few days. 
They are then removed by the recipient’s 
immune cells. In patients with weak-
ened or immature immune systems or 
in HLA-homozygous donors and HLA-
heterozygous recipients, the allogeneic 
donor T lymphocytes are not removed 
from the recipient’s bloodstream; they are 
activated and multiply instead. Specific 
cytokines are secreted in multiplication 
and differentiation of T lymphocytes, in-
terferon γ (IFN γ) and interleukin 2 (IL-2) 
to the greatest extent. This triggers the ac-
tivation of natural killer cells (NK), mac-
rophages and other lymphocyte subpopu-
lations. This then leads to apoptosis of the 
recipient’s cells and injury of their organs 
and tissues, which is clinically expressed 
as TA-GvHD (1,2).
TA-GvHD is clinically indistinguish-
able from the acute form of GvHD follow-
ing haematopoietic stem-cell transplan-
tation (HSCT). The difference is only in 
the time it takes for symptoms to appear; 
TA-GvHD becomes clinically evident 
sooner, in only a few days. It is usually not 
Cite as/Citirajte kot: Barbarić Kovačić A, Stanišić S, Zver S. Transfusion associated graft vs. host disease and 
how to prevent it. Zdrav Vestn. 2021;90(3–4):193–201.
DOI: https://doi.org/10.6016/ZdravVestn.3009
Copyright (c) 2021 Slovenian Medical Journal. This work is licensed under a
Creative Commons Attribution-NonCommercial 4.0 International License.
recognized and the clinical course is rapid 
and always leads to bone marrow aplasia 
(3).
As no effective treatment exists for 
TA-GvHD, prevention is key. Patients at 
risk of developing TA-GvHD need to be 
identified. They should only receive irra-
diated blood units and platelets, treated 
with UVA psoralen-based pathogen in-
activation. The knowledge, awareness and 
approach of the attending physician and 
transfusion medicine specialist is crucial 
(4).
Blood units (erythrocytes, granulo-
cytes, platelets that have not been patho-
gen inactivated, and fresh blood plasma 
that has not been frozen) are always irra-
diated prior to transfusion. For platelets, 
the equivalent to irradiation is UVA pso-
ralen-based pathogen inactivation.
Fresh frozen plasma, cryoprecipitate, 
blood-derived medicines, such as albu-
mins, immunoglobulins, blood clotting 
factors, and erythrocytes after thawing 
and washing do not need to be irradiated 
since their T lymphocyte content is negli-
gible (4,5).
2 History
In 1955, Shimoda first described cases 
of so-called postoperative erythroderma 
(POED) in 12 patients who received fresh 
blood from their relatives (1,2). All of 
them became ill with fever and rash 6–13 
days following the transfusion and later 
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Transfusion associated graft vs. host disease and how to prevent it
died. At first, the cause was presumed to 
be an allergic drug reaction. Only later was 
it recognized that these were the first de-
scribed cases of TA-GvHD. The first case 
of TA-GvHD in an immunocompetent pa-
tient was described in Japan in 1984. More 
than 340 cases have been described in the 
literature so far. The disease is often not 
recognized, so the number of published 
TA-GvHD cases in the literature is cer-
tainly lower than the actual number (2).
3 Patient factors important for 
the development of TA-GvHD
• A weakened or immature immune 
system of the blood unit recipient
Patients at highest risk for the devel-
opment of TA-GvHD are those with con-
genital or acquired immunodeficiency. 
Because of their weakened immune sys-
tems, these patients do not mount an ap-
propriate immune response to donor lym-
phocytes, which survive in the recipient’s 
body and multiply in the bone marrow. 
They cause apoptosis of bone marrow cells 
and injure the recipient’s tissues.
• The recipient is immunocompetent, 
but there is a partial HLA compatibil-
ity between the donor and recipient, 
which leads to the recipient’s immune 
system not recognizing the donor T 
lymphocytes as foreign, so they are 
not removed from the bloodstream. 
Partial HLA compatibility between 
the HLA-homozygous recipient and an 
HLA-heterozygous volunteer blood do-
nor is associated with the highest risk for 
the development of TA-GvHD in immu-
nocompetent patients. The HLA compat-
ibility “blinds” the recipient’s otherwise 
immunocompetent cells to allow implan-
tation of donor T lymphocytes, which 
then trigger TA-GvHD. The HLA immune 
tolerance of the recipient’s immune system 
is not welcome in such cases. The risk for 
patients with a specific HLA haplotype 
to receive blood from a donor, HLA-
homozygous for this haplotype, in a het-
erogenous white population in the USA is 
1/17,700–39,000. In Germany, the risk for 
the development of TA-GvHD is 1/6.900–
48.500, and in Japan, the risk is signifi-
cantly higher at 1/1,600–7,900. The dif-
ferences can be explained by regions with 
reduced genetic variability (6). For this 
reason, Japan introduced the irradiation 
of all blood units in 2000, and since then, 
no cases of TA-GvHD have been report-
ed there (7). In Slovenia, this is a realistic 
possibility especially for treatment with 
granulocyte products. Not uncommonly, 
the donors are relatives of the patient.
• The number of viable T lymphocytes 
in a blood unit
Although the smallest number of vi-
able T lymphocytes in a blood unit nec-
essary for the development of TA-GvHD 
is not known, the data from the literature 
show that at least 1x107 of T lymphocytes/
kg of the patient are needed for TA-GvHD 
to develop after their multiplication, pro-
liferation, and apoptosis of the recipient’s 
tissues. Blood units that meet this “condi-
tion” are whole blood (not available any-
more in Slovenia), concentrated erythro-
cytes (1-2x109 per therapeutic dose, TD); 
whole blood-derived platelets (4x107 per 
TD); apheresis platelets (3x108 per TD); 
granulocyte concentrates (5-10x109 per 
TD); nonfrozen liquid plasma, which 
has not been used in Slovenia for several 
years. Fewer than 1x107/kg of the patient 
of lymphocytes are present in frozen de-
glycerized erythrocytes (5x107 per TD) 
and fresh frozen plasma (8x104 per TD). 
Cryoprecipitate, which is also not used 
in Slovenia anymore, does not contain T 
lymphocytes. (8). Transfusion centres are 
responsible for an adequately low content 
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of T lymphocytes in blood units, using 
modern preparation and processing meth-
ods to guarantee their quality.
• The volume and age of the blood unit
The lifespan and activity of lympho-
cytes depend on the age of the blood prod-
uct. Lymphocytes are most viable in the 
first three days after blood collection, then 
their activity falls exponentially. Studies 
have shown that there are no active T lym-
phocytes in erythrocyte products after 
three weeks. Therefore, the transfusion of 
fresh blood (not available for treatment in 
Slovenia) is an additional risk factor for 
patients already at risk for TA-GvHD (9).
4 Patient groups at risk for the 
development of TA-GvHD
Paediatric patients: In the paediatric 
population, the most at-risk for TA-GvHD 
are neonates with a low birth weight and 
the prematurely born—the latter especial-
ly if they previously received intrauterine 
transfusions (IUT), children with congen-
ital deficiencies of cell-mediated immuni-
ty (e.g. thymic hypoplasia – DiGeorge syn-
drome, Wiskott-Aldrich syndrome, severe 
combined immunodeficiency (SCID)), 
and children with severe immunodefi-
ciency due to chemotherapy or radiation 
for the treatment of oncological or auto-
immune diseases. All of them should only 
be treated with irradiated blood units (8).
Patients with haematological diseas-
es: Adults and children with Hodgkin’s 
lymphoma; patients with non-Hodgkin’s 
lymphoma and acute leukaemia who re-
ceive treatment with nucleoside analogues 
(clofarabine, cladribine, fludarabine, 
nelarabine); some believe that irradiated 
blood units should also be used in pa-
tients treated with bendamustine (5); pa-
tients treated with anti-lymphocyte glob-
ulin (aplastic anaemia, myelodysplastic 
syndrome); patients with deficiency of 
cell-mediated immunity.
Haematopoietic stem-cell transplan-
tation: After allogeneic or autologous 
HSCT, patients should only be treated with 
irradiated blood units, without exception. 
Irradiation begins at the start of condi-
tioning for HSCT. To avoid TA-GvHD, pa-
tients require irradiated blood units for at 
least 6 months after allogeneic HSCT and 
3 months after autologous HSCT or for as 
long as the number of lymphocytes is be-
low 1x109/L, if the patient is receiving im-
munosuppressive drugs. In case of chronic 
GvHD, only irradiated blood units should 
be used. Should donors of bone marrow 
and hematopoietic stem cells from periph-
eral blood need a transfusion of allogeneic 
blood units seven days before or during 
the harvesting procedure, such blood 
units should also be irradiated. Solid or-
gan transplant recipients do not need irra-
diated blood units unless they are treated 
with immunosuppressive drugs (5,10).
The drugs are listed in Table 1.
Solid tumours: TA-GvHD is not al-
ways associated with the type of tumour 
but with the type and intensity (degree of 
immunosuppression) of chemotherapy, 
which causes immunosuppression and 
creates the conditions for the growth of 
donor T lymphocytes. Cases of TA-GvHD 
in patients with neuroblastoma, rhabdo-
myosarcoma, lung cancer, etc., are de-
scribed in the literature (2).
Indications for irradiation of blood 
units are listed in Table 2.
5 Clinical features of TA-GvHD
The clinical features are varied and only 
appear with a delay after receiving a blood 
unit. Establishing a diagnosis is, therefore, 
often difficult. The first symptoms and 
Table 1: Generic and brand names of drugs, capable of causing the development of TA-GvHD.
Immunosuppressive drugs, capable of causing the development of TA-GvHD
Generic name Brand name in Slovenia
fludarabine, nelarabine Fludara
cladribine (2-CDA) Litak
deoxycoformycin Pentostatin
alemtuzumab (anti-CD52) Lemtrada, Campath
anti-thymocyte globulin (ATG) Atgam
bendamustine Bendamustine actavis, Levact, Lynetoril
clofaribine Evoltra
Table 2: Patients with indications for blood unit irradiation.
Paediatric patients
• Intrauterine transfusions (IUT)
• Exchange transfusions (ET)
• Neonates with a low birth weight and the prematurely born
• Children with congenital deficiencies of cell-mediated immunity (DiGeorge syndrome, Wiskott-
Aldrich syndrome, severe combined immunodeficiency (SCID). All are indications for lifelong blood 
unit irradiation
Haematologic patients (children and adults)
• Haematopoietic stem-cell transplantation (HSCT) (autologous for 3 months and allogeneic for 6 
months after HSCT)
• Acute myeloblastic leukaemia (AML)
When treated with purine analogues• Acute and chronic myeloblastic leukaemia (ALL, CLL)
• Non-Hodgkin lymphoma (NHL)
• Hodgkin lymphoma Lifelong
• Solid organ transplant recipients, when they are treated with alemtuzumab
• Recipients of blood units from biological relatives 
• Recipients of blood units from HLA-compatible donors
• Recipients of granulocyte concentrates 
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Transfusion associated graft vs. host disease and how to prevent it
syndrome); patients with deficiency of 
cell-mediated immunity.
Haematopoietic stem-cell transplan-
tation: After allogeneic or autologous 
HSCT, patients should only be treated with 
irradiated blood units, without exception. 
Irradiation begins at the start of condi-
tioning for HSCT. To avoid TA-GvHD, pa-
tients require irradiated blood units for at 
least 6 months after allogeneic HSCT and 
3 months after autologous HSCT or for as 
long as the number of lymphocytes is be-
low 1x109/L, if the patient is receiving im-
munosuppressive drugs. In case of chronic 
GvHD, only irradiated blood units should 
be used. Should donors of bone marrow 
and hematopoietic stem cells from periph-
eral blood need a transfusion of allogeneic 
blood units seven days before or during 
the harvesting procedure, such blood 
units should also be irradiated. Solid or-
gan transplant recipients do not need irra-
diated blood units unless they are treated 
with immunosuppressive drugs (5,10).
The drugs are listed in Table 1.
Solid tumours: TA-GvHD is not al-
ways associated with the type of tumour 
but with the type and intensity (degree of 
immunosuppression) of chemotherapy, 
which causes immunosuppression and 
creates the conditions for the growth of 
donor T lymphocytes. Cases of TA-GvHD 
in patients with neuroblastoma, rhabdo-
myosarcoma, lung cancer, etc., are de-
scribed in the literature (2).
Indications for irradiation of blood 
units are listed in Table 2.
5 Clinical features of TA-GvHD
The clinical features are varied and only 
appear with a delay after receiving a blood 
unit. Establishing a diagnosis is, therefore, 
often difficult. The first symptoms and 
Table 1: Generic and brand names of drugs, capable of causing the development of TA-GvHD.
Immunosuppressive drugs, capable of causing the development of TA-GvHD
Generic name Brand name in Slovenia
fludarabine, nelarabine Fludara
cladribine (2-CDA) Litak
deoxycoformycin Pentostatin
alemtuzumab (anti-CD52) Lemtrada, Campath
anti-thymocyte globulin (ATG) Atgam
bendamustine Bendamustine actavis, Levact, Lynetoril
clofaribine Evoltra
Table 2: Patients with indications for blood unit irradiation.
Paediatric patients
• Intrauterine transfusions (IUT)
• Exchange transfusions (ET)
• Neonates with a low birth weight and the prematurely born
• Children with congenital deficiencies of cell-mediated immunity (DiGeorge syndrome, Wiskott-
Aldrich syndrome, severe combined immunodeficiency (SCID). All are indications for lifelong blood 
unit irradiation
Haematologic patients (children and adults)
• Haematopoietic stem-cell transplantation (HSCT) (autologous for 3 months and allogeneic for 6 
months after HSCT)
• Acute myeloblastic leukaemia (AML)
When treated with purine analogues• Acute and chronic myeloblastic leukaemia (ALL, CLL)
• Non-Hodgkin lymphoma (NHL)
• Hodgkin lymphoma Lifelong
• Solid organ transplant recipients, when they are treated with alemtuzumab
• Recipients of blood units from biological relatives 
• Recipients of blood units from HLA-compatible donors
• Recipients of granulocyte concentrates 
signs appear 4–30 days after a blood unit 
transfusion, which makes it difficult to 
establish a diagnosis as the link between 
the transfusion and TA-GvHD is often 
missed. The clinical features are charac-
teristic of acute or chronic GvHD, as is 
seen with treatment of allogeneic HSCT. 
The latter, however, does not feature bone 
marrow aplasia on a bone marrow biopsy, 
as is characteristic of TA-GvHD. The skin, 
intestines and liver are primarily affect-
ed, but any organ system can also be in-
volved. A skin rash is usually the first clin-
ical sign, appearing in an erythematous 
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or maculopapular form and usually pro-
gressing to generalised erythroderma 
or, in extreme cases, to toxic epidermal 
necrolysis. The most common intestinal 
signs and symptoms are anorexia, vomit-
ing, elevated transaminases, hepatomega-
ly, abdominal pain and profuse diarrhoea 
(up to 7–8 L/day). Bone marrow involve-
ment is manifested by pancytopenia in the 
peripheral blood, a consequence of bone 
marrow aplasia. Clinically, such patients 
may have a fever (febrile neutropenia) and 
are vulnerable to respiratory and urinary 
tract infections or they can experience 
spontaneous bleeding (11).
TA-GvHD mortality exceeds 90% due 
to a lack of effective treatment. Prevention 
is the only acceptable course. TA-GvHD is 
confirmed with histological examination 
of the affected organ or tissue or with con-
firmation of lymphocyte chimerism.
In neonates, TA-GvHD is overlooked 
more often than in adults as it appears lat-
er; the clinical features are often attributed 
to prematurity itself and comorbidities. 
Cutaneous erythema, usually the first clin-
ical sign of the disease, is often attributed 
to incubator use or phototherapy with liv-
er immaturity (12).
6 Diagnosis and treatment of 
TA-GvHD
The first and most important step in 
diagnosing TA-GvHD is to think of the 
disease in time. It can be easily missed as 
it can be attributed to general poor con-
dition, viral, bacterial or fungal infec-
tions, autoimmune diseases or side effects 
of treatment. A good history, focused on 
possible immunodeficiency, is key when 
admitting patients for treatment planning.
If pancytopenia, skin rash or intestinal 
problems appear in the first month follow-
ing a blood transfusion, TA-GvHD should 
always be thought of and a consultation 
with attending transfusion medicine spe-
cialist should be sought. They will check 
whether the received blood units were ir-
radiated or pathogen inactivated (2).
TA-GvHD is confirmed with flow cy-
tometry, with which we can detect donor 
lymphocytes in the recipient’s peripheral 
blood, or histologically with the proof of 
presence of donor HLA antigens or DNA.
Donor T lymphocyte detection tech-
niques are HLA typing, variable numbers 
of tandem repeats (VNTR), karyotyping 
or analysis of microsatellite DNA loci. 
Donor DNA can be isolated from blood 
or cell infiltrations and confirmed with a 
polymerase chain reaction (PCR).
No effective treatment for TA-GvHD 
is known. Treatment with immunosup-
pressive drugs, including corticosteroids, 
is almost without effect. Trials of treat-
ment with cyclosporine, anti-lymphocyte 
globulin, methotrexate, azathioprine, ser-
ine protease inhibitors, chloroquine and 
OKT3 have been described (13,14). Even 
treatment with combinations of drugs, 
for example cyclosporine and anti-CD3 
monoclonal antibodies or anti-lympho-
cyte globulin and steroids, has not brought 
the desired results (15). Treatment with 
extracorporeal photopheresis (ECP) with 
the aim of triggering donor lymphocyte 
apoptosis and acting as an anti-inflamma-
tory can be tried. Allogeneic HSCT is the 
only successful treatment method, but it 
is rarely considered as there is usually not 
enough time to find for a suitable donor. 
This could change, however, with the ad-
vent of haploidentical HSCT. A poor re-
sponse to treatment and high mortality 
sadly remain characteristic of TA-GvHD.
7 Prevention of TA-GvHD
TA-GvHD is an incurable disease with 
a high mortality rate. Prevention is thus 
key. Methods of prevention are: blood unit 
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Transfusion associated graft vs. host disease and how to prevent it
irradiation, UVA psoralen-based patho-
gen inactivation of platelets and reducing 
the number of T lymphocytes in a blood 
unit (4).
The most effective method for inac-
tivating lymphocytes in a blood unit is 
with ionizing radiation. With irradiation, 
the DNA of nucleated cells is denaturat-
ed, thus preventing them from dividing, 
which prevents the multiplication of all 
lymphocyte subpopulations. At the Blood 
Transfusion Centre of Slovenia (BTC), 
irradiation of blood units has been used 
since 2007 for all Slovenian patients. The 
Gammacell 1000 Elite irradiator is used 
for this purpose. The source of radiation 
is the Cs-137 isotope. The ordinary radi-
ation dose for all blood products is 30 Gy. 
Since 2020, the new Radgil 2 irradiation 
has been used and is equally effective as 
the Gammacell 1000 Elite. Its advantage is 
greater safety for providers as X-rays are 
used as the source of radiation. There is 
no data in the literature on X-rays causing 
slight damage to blood cell membranes. 
The British Council for Standards in 
Haematology (BCSH) recommends a radi-
ation dose of 25–50 Gy (5). The American 
Association of Blood Banks (AABB) rec-
ommends a minimal radiation dose of 25 
Gy with no part of the blood unit receiv-
ing less than 15 Gy, but no more than 50 
Gy (16). The same recommendations are 
in use in Japan (7). With a radiation dose 
of 30 Gy, we are therefore following the 
published recommendations in Slovenia.
Another effective way to prevent the 
development of TA-GvHD is pathogen 
inactivation. A combination of psoralen 
(amotosalen) and UVA rays is used to 
prevent the replication of viruses, bacte-
ria, parasites and also lymphocyte pro-
liferation. Pathogen inactivation with 
Intercept® (amotosalen/UVA) is used by 
the BTC. Currently, the method is only 
suitable for whole blood-derived platelets 
and apheresis platelets. Irradiation is not 
needed after platelets have been inactivat-
ed with psoralen. 
The smallest number of T lymphocytes 
that are capable of causing TA-GvHD has 
not yet been established. The number of 
lymphocytes in blood units could be re-
duced with filtration or washing. These 
procedures are not effective enough, 
however, to prevent the development of 
TA-GvHD. This is confirmation that TA-
GvHD can develop in immunocompetent 
patients after transfusion of filtered blood 
units (4).
8 Side effects of irradiation on 
blood unit quality
Irradiation of erythrocyte products 
damages the erythrocyte membrane by 
damaging the Na+/K+ pump, reducing 
erythrocyte viability. This leads to an in-
crease in the extracellular concentration 
of K+ and an influx of Na+ into erythro-
cytes as a consequence of ATP depletion 
in erythrocytes. ATP is, of course, the “fu-
el” for the Na+/K+ pump. Conversely, the 
haemoglobin and lactate dehydrogenase 
(LDH) levels in the supernatant of the ir-
radiated blood unit rise. The changes in 
the membrane and the impaired opera-
tion of the Na+/K+ pump affect the dura-
bility of the erythrocyte membrane, which 
can lead to haemolysis due to lower mem-
brane compliance. After erythrocyte irra-
diation, the K+ concentration in a stored 
blood unit rises by 1–2 meQ/day. Caution 
is therefore recommended in patients with 
kidney failure, intrauterine transfusion 
(IUT) and exchange transfusion (ET). 
The time between irradiation and transfu-
sion is limited to 24 hours in such cases 
(9). Irradiation of platelets does not affect 
their number, morphology or function. 
As most platelet products in Slovenia go 
through UVA psoralen-based pathogen 
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inactivation, they do not need additional 
irradiation. Following irradiation, the ba-
sic functions of granulocytes (chemotaxis, 
phagocytosis and generation of free rad-
icals) are not altered, so their function is 
not impaired.
9 Conclusion
TA-GvHD is an extremely rare but 
life-threatening complication of blood 
transfusion with a dismal prognosis. 
Therefore, it is necessary to spread knowl-
edge and raise awareness in the profes-
sion on how to prevent this complication. 
Awareness of the disease should reach all 
healthcare workers, physicians, transfu-
sion medicine specialists and the patients 
themselves. The patients at risk of devel-
oping TA-GvHD need to be identified 
and provided with safe, irradiated blood 
units. Patients need to be aware of their 
medication and whether they are immu-
nodeficient. Only in this way can they 
warn their physician of the possible com-
plication. Cooperation, dialogue between 
all involved in the patient’s management, 
and flow of information between clini-
cians and transfusion medicine specialists 
are key. The responsibility of the transfu-
sion medicine specialist lies in ensuring 
the irradiation of blood products is done 
in accordance with established standard-
ized procedures and that the quality meets 
the maximum safety requirements for the 
recipient.
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Transfusion associated graft vs. host disease and how to prevent it
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