Guidelines on the use of irradiated blood components prepared by the British Committee for Standards in Haematology blood transfusion task force

Abstract

The following were searched systematically for publications in English, until June, 2009: PubMed – from 1950 Medline – from 1950 EMBASE – from 1980 CINAHL (Cumulative Index to Nursing and Allied Health Literature) – from 1982 The Cochrane Library 2008, Issue 3 DARE CRD Website (Centre for Reviews and Dissemination) SRI (Systematic Review Initiative) Handsearch Databases Search terms included: Transfusion-associated graft-versus-host disease, Transfusion-associated graft-versus-host, TA-GvHD. The last guideline covering this topic was published in 1996 (British Committee for Standards in Haematology (BCSH) Blood Transfusion Task Force, 1996. The writing group produced the new draft guideline, which was subsequently revised by consensus by members of the Haemato-oncology and Blood Transfusion Task Forces of the BCSH. The guideline was then reviewed by a sounding board of approximately 100 UK haematologists, the BCSH and the committee of the British Society for Haematology and amended, again by consensus. Criteria used to quote levels and grades of evidence are according to the GRADE system (Guyatt et al, 2006). Strong recommendations (grade 1, ‘recommended’) are made when there is confidence that the benefits either do or do not outweigh the harm and burden and costs of treatment. Where the magnitude of benefit or not is less certain a weaker grade 2 recommendation (‘suggested’) is made. Grade 1 recommendations can be applied uniformly to most patients whereas grade 2 recommendations require judicious application. The quality of evidence is graded as A (high quality randomized clinical trials), moderate (B) or low (C). This publication reports the key recommendations of the Writing Group. It is also accessible at http://www.bcshguidelines.com. To provide healthcare professionals with clear guidance on situations when the use of irradiated blood components is appropriate, and to document any recognized advantages and disadvantages of their use. The guidance may not be appropriate in all patient situations, and individual circumstances may dictate an alternative approach. Studies of patients in all age groups have been considered. • Use of X-irradiation as an alternative to gamma irradiation. • All cases of transfusion-associated graft-versus host disease and all episodes where non-irradiated components are transfused to high risk patients should be reported to national haemovigilance systems [in the UK, the Serious Hazards of Transfusion (SHOT) initiative]. • Irradiated components are recommended for aplastic anaemia patients receiving immunosuppressive therapy with anti-thymocyte globulin (ATG). • Indication for irradiated components extended to newer purine analogues and related drugs until evidence of their safety is forthcoming (e.g. bendamustine and clofarabine). • Irradiated components indicated for patients receiving the biological immunosuppressive agent alemtuzumab (anti-CD52), but not rituximab (anti-CD20) – regular review will be needed as new biological agents enter clinical practice. • All cases of transfusion-associated graft-versus-host disease (TA-GvHD) should be reported to the national haemovigilance system, as should all ‘near misses’ where non-irradiated components are transfused to high-risk patients without incident (1B). • Gamma or X-irradiation of blood components, by validated systems, is the recommended procedure to prevent TA-GvHD (1B). • The minimum dose achieved in the irradiated volume should be 25 Gy, with no part receiving more than 50 Gy (1B). • For at-risk patients, all red cell, platelet and granulocyte concentrates should be irradiated except cryopreserved red cells after deglycerolization. It is not necessary to irradiate fresh frozen plasma, cryoprecipitate or fractionated plasma products (1B). • All donations from first- or second-degree relatives should be irradiated, even if the patient is immunocompetent (1B). • All human leucocyte antigen (HLA)-selected components should be irradiated, even if the patient is immunocompetent (2C). • Red cells may be irradiated at any time up to 14 d after collection, and thereafter may be stored for a further 14 d. Where the patient is at particular risk from hyperkalaemia, e.g. intrauterine or neonatal exchange transfusion, it is recommended that red cells be transfused within 24 h of irradiation or that the cells are washed (1A). • Platelets can be irradiated at any stage during storage and can thereafter be stored up to their normal shelf life after collection (1A). • All granulocyte components should be irradiated before issue and transfused with minimum delay (1C). • Irradiated components not used for the intended recipient can safely be returned to stock to be used for recipients who do not require irradiated components. The reduction in shelf life must be observed (1B). • All irradiated components should be labelled as such, using an approved bar code label. Each unit should be monitored using a radiation-sensitive device, and the result permanently recorded, manually or by computer (1C). • All blood for intrauterine transfusion (IUT) should be irradiated (1B). It is essential to irradiate blood for neonatal exchange transfusion (ET) if there has been a previous IUT or if the donation comes from a first- or second-degree relative (1B). For other neonatal ET cases, irradiation is recommended provided this does not unduly delay transfusion (1C). For IUT and ET, blood should be transfused within 24 h of irradiation and, in any case, by 5 d or less from collection (1A). • It is not necessary to irradiate red cells for routine ‘top-up’ transfusions of premature or term infants unless either there has been a previous IUT, in which case irradiated components should be administered until 6 months after the expected delivery date (40 weeks gestation), or the donation has come from a first- or second-degree relative (2C). • Platelets transfused in utero to treat alloimmune thrombocytopenia should be irradiated and any subsequent red cell or platelet transfusions irradiated until 6 months after the expected date of delivery (40 weeks gestation). There is no need to irradiate other platelet transfusions for pre-term or term infants, unless they have been donated by first- or second-degree relatives (1C). • All severe T lymphocyte immunodeficiency syndromes should be considered as indications for irradiation of cellular blood components. Once a diagnosis of immunodeficiency has been suspected, irradiated components should be given while further diagnostic tests are A clinical should be for in cases where there is (1A). • There is no for routine irradiation of cellular blood components for infants or who are from a who are human immunodeficiency or who have immunodeficiency this should be There is also no for routine irradiation of cellular blood components for who are or who have • There is no need to irradiate red cells or for infants unless clinical or a T lymphocyte immunodeficiency • It is not necessary to irradiate red cells or for or with except for or donations from first- or second-degree relatives (1B). • All recipients of cell must irradiated blood components from the time of of (1B). This should be while the patient to graft-versus-host disease for 6 months or until are is or if immunosuppressive is irradiated blood components should be given (2C). blood transfused to and blood cell d to or during the should also be irradiated (2C). • or blood cell for should irradiated cellular blood components during and for d before the cell to prevent the collection of T which can (2C). • All patients or blood cell should irradiated cellular blood components from of until 3 months months if irradiation was used in (2C). • All and with at any stage of the disease should have irradiated red cells and for life (1B). • with purine drugs and should irradiated blood components (1B). The with other purine and new and related as bendamustine and is but use of irradiated blood components is recommended as agents have a of Irradiated blood components should be used after alemtuzumab use after rituximab (anti-CD20) is not recommended at this new drugs and biological agents are there is a need for regular review of recommendations (2C). • It is not necessary to irradiate blood components for patients routine with or after alemtuzumab has been used in the The of new of and clinical must to be monitored (2C). • of the from anti-thymocyte globulin to the more immunosuppressive use of irradiated blood components for aplastic anaemia patients receiving immunosuppressive therapy with (2C). a recommendation as to irradiated components should to be used after • at risk of TA-GvHD should be made of their need for irradiated blood components and provided with appropriate and an for clinical the recommendations from to clinical and and of for transfusion, irradiated components. to and clinical systems with and diagnostic to should be and in of patients is a and the of a national system for and of transfusion is an to patient (2C). recommendations on transfusion are are given in the BCSH of Blood for patients and healthcare are from the UK Blood a of the key TA-GvHD is a but following transfusion of blood components. the reports cases where been transfused recipients et al, et al, it that patients also this if the blood components they from an or et al, et al, et al, et al, et al, The risk with an individual transfusion on the and of of the system to their and of and The minimum of transfused necessary to a is and may by clinical gamma irradiation of cellular blood components has been the of TA-GvHD and was in the UK following publication of the 1996 of this BCSH Blood Transfusion Task Force, TA-GvHD is a of transfusion of any blood T when there is in the and as the and in after cell TA-GvHD is by and in of et al, et al, There is a particular risk of TA-GvHD when the and patient an as within et or in with et al, the the of TA-GvHD is than in the et The are and weeks after severe with is made by of or by evidence of of The of cells of may be by in blood et al, or using blood and from and in the and blood from the et al, in the UK Serious Hazards of Blood Transfusion (SHOT) has cases of TA-GvHD et al, et al, cases have been reported the of in the UK et al, and no cases have been reported 1996 and 2008, reports of cases where non-irradiated components been transfused to high-risk of the purine but TA-GvHD. This that has if not the risk of TA-GvHD et al, • All cases of transfusion-associated graft-versus-host disease (TA-GvHD) should be reported to the national haemovigilance system, as should all ‘near misses’ where non-irradiated components are transfused to high-risk patients without 1 The for TA-GvHD is irradiation of blood components to Gamma and are in their to T in blood components at a given are and and may a risk in the regular is and irradiation time blood are have been used in for and are by the UK Transfusion irradiation are less and the of a in et al, that the in red cell and components are not et al, by the Committee of the UK Transfusion on blood components irradiated using the that gamma and X-irradiation can be as and are and for clinical use. • Gamma or X-irradiation of blood components, by validated systems, is the recommended procedure to prevent TA-GvHD. 1 Studies using that a dose of 25 Gy, at the of a lymphocyte et al, The of Blood a dose of 25 Gy to the of the with no receiving Gy 2006). The Society of Blood a dose et al, the UK, a minimum of 25 Gy is but with the dose to any in the not 50 To this dose is with is et al, • The minimum dose achieved in the irradiation volume should be 25 Gy, with no part receiving more than 50 1 is in stored red cells for at 3 weeks and TA-GvHD has been reported after transfusion of red and et al, TA-GvHD has not been following transfusion of frozen red which are washed of after TA-GvHD has not been following transfusion of fresh frozen plasma or fractionated plasma as and • For at-risk patients, all red cell, platelet and granulocyte components should be irradiated, except cryopreserved red cells after deglycerolization. It is not necessary to irradiate fresh frozen plasma, cryoprecipitate or fractionated 1 of the of donations from members a particular risk of TA-GvHD. Red and fresh plasma have all been in TA-GvHD after transfusion from members et and there is an risk with donations from first- and second-degree cases of TA-GvHD have been reported from where of in the the of a transfusion recipient receiving blood from a or are of for patients receiving platelet concentrates from members of alloimmune to This be expected to the risk of if the platelet is for of the recipient to donations within or within groups of A case of TA-GvHD in an immunocompetent recipient following transfusion of blood components from an was reported et al, and more cases were reported from in immunocompetent recipients who non-irradiated blood from relatives et al, The risk from where the is not is transfusion of for patients, and in it is more to irradiation of all than risk the of • All transfusions from first- or second-degree relatives should be irradiated, even if the patient is immunocompetent 1 • All should be irradiated, even if the patient is 2 irradiation of blood components a The is expected to with of the to Red cells can be irradiated up to 14 d after collection and stored for at a further 14 d without of Gamma irradiation may result in red cell after more is the minimum et al, gamma and X-irradiation of red cells result in of and an in the of et al, et al, et al, transfusions given at do not a risk of hyperkalaemia, even when given to premature may be in as neonatal exchange transfusion or intrauterine of plasma and of irradiated red cells is not considered necessary if this procedure is the washed cells should be transfused as as within levels are in stored irradiated red cell components et al, but within has no on red cell or levels et • Red cells may be irradiated at any time up to 14 d after collection, and thereafter stored for a further 14 d from irradiation. Where the patient is at particular risk from hyperkalaemia, e.g. intrauterine or neonatal exchange transfusion, it is recommended that red cells be transfused within 24 h of irradiation or that the cells are 1 A Gamma irradiation 50 Gy has not been to clinical in platelet et al, et al, et al, • Platelets can be irradiated at any stage during storage and can thereafter be stored up to their normal shelf life after 1 A The evidence for irradiation to granulocyte is but in any case granulocyte products should be transfused as as after irradiation et al, et al, • All should be irradiated before issue and transfused with minimum 1 It is that the dose of gamma irradiation to blood components the dose for cells at high dose in cell than of Gamma irradiation can and result in of the recipient et al, et al, cases have been reported and the with of of from the transfusion is a risk for recipients of transfusions of irradiated components et al, for The of irradiation on the new and used in the of blood and • Irradiated components not used for the intended recipient can safely be returned to stock to be used for recipients who do not require irradiated components. The reduction in shelf life must be 1 Irradiated components must be by an approved label. The should be and the date of irradiation and any reduction in shelf bar code should be that components have been irradiated is that are to irradiation and from to are The dose at which the to must be on the label. using a radiation-sensitive on can also be using The use of radiation-sensitive does not the need for regular and There should be a of all irradiated, of irradiation and donation the of when irradiation was and by • All irradiated should be labelled as such, using an approved bar code label. Each unit should be monitored using a radiation-sensitive device, and the result should be permanently recorded, manually or by 1 at risk of TA-GvHD. The if may be at particular risk of TA-GvHD of may be in the neonatal weeks after exchange transfusion (ET) et al, and cells have been after intrauterine transfusion (IUT) for disease of the and after transfusion in cases of TA-GvHD reported in infants have in the of IUT by ET et al, or IUT the reported cases of TA-GvHD following IUT from et al, it is not to irradiation in the of a transfusion of fresh blood to a IUT and subsequent exchange reports are the published evidence a of irradiation of blood for IUT and any subsequent et al, transfusion cases of TA-GvHD have been reported after ET in pre-term and term infants et al, et the of irradiation of blood for ET in either pre-term or term infants is but not The risk of TA-GvHD must be of any delay in transfusion while irradiation is • All blood for intrauterine transfusion (IUT) should be 1 • Blood for neonatal exchange transfusion (ET) must be irradiated if there has been a previous IUT or if the donation comes from a first- or second-degree 1 • For other neonatal ET cases, irradiation is recommended provided this does not unduly delay 1 • For IUT and ET, blood should be transfused within 24 h of irradiation and, in any case, by 5 d or less from 1 A infants are transfused there are reports of TA-GvHD age the of transfusions to and the term or of to transfused in the of transfusions with there has been reported case of TA-GvHD et al, and infants do not to be at • It is not necessary to irradiate red cells for routine ‘top-up’ transfusions of premature or term infants unless either there has been a previous IUT, in which case irradiated components should be administered until 6 months after the expected delivery date (40 weeks gestation), or the donation has come from a first- or second-degree 2 There have been no reported cases of TA-GvHD following platelet transfusion but as may of the recommendations for red cell transfusion should also to should be on transfused in utero to treat alloimmune thrombocytopenia and on platelet transfusions given after to infants who have either red cells or in utero for 6 months after the expected delivery • Platelets transfused in utero to treat alloimmune thrombocytopenia should be irradiated and any subsequent red cell or platelet transfusions irradiated until 6 months after the expected date of delivery (40 weeks gestation). There is no need to irradiate other platelet transfusions for pre-term or term infants, unless they have been donated by first- or second-degree 1 There have been no cases of TA-GvHD to components are with and transfused it is to irradiate all granulocyte transfusions for and • All granulocyte transfusions should be irradiated for recipients of any and they should be transfused as as after irradiation. 1 TA-GvHD has been reported in with severe T lymphocyte by an of T or a severe of T cell the the of immunodeficiency syndromes may be to the (e.g. disease, and a high of is in infants less than 6 months with or or To there have been no reports of TA-GvHD in patients with of • All severe T lymphocyte immunodeficiency syndromes should be considered as indications for irradiation of cellular blood components. Once a diagnosis of immunodeficiency has been suspected, irradiated components should be given while further diagnostic tests are A clinical should be for in cases where there is 1 A of T cell can following and in the of and TA-GvHD has not been reported in situations and irradiation of blood components is not the T cell in no cases of TA-GvHD have been in or • There is no for irradiation of cellular blood components for infants or who are from a who are or who have this should be There is also no for irradiation of cellular blood components for who are or who have 2 There have been published reports of TA-GvHD in immunocompetent et al, and there should be a high of and in blood should be irradiated until a diagnosis is made. an immunodeficiency as or with severe T lymphocyte is irradiated components are for for with as and or in is suspected, should also irradiated blood components as the risk of TA-GvHD is • There is no need to irradiate red cells or for infants unless clinical or a T lymphocyte immunodeficiency 2 • and Blood in and There are published reports of TA-GvHD in patients receiving without cell and, there has been case reported in et al, there have been and cases reported in the of and in the UK, no irradiate blood components for patients with without and no cases of TA-GvHD have been reported to • It is not necessary to irradiate red cells or for or with except for or donations from first- or second-degree 1 For the last it has been to irradiate blood components transfused to cell There is no A evidence to when irradiation of blood components can safely be with the of for Blood and et al, that irradiation should be at until immunosuppressive therapy is 6 months in most an require blood transfusion within d before components should be that irradiated components should be used for patients with • All recipients of cell must irradiated blood components from the time of of 1 • Irradiated components should be while the patient to graft-versus-host disease for 6 months or until the lymphocyte is is or if immunosuppressive is irradiated blood components should be given 2 • blood transfused to and blood cell d to or during the should also be 2 all UK irradiate blood components for recipients and most use irradiated components before and during of or blood evidence does not when irradiation can be safely a irradiated blood components should be used until there is evidence of and 3 months with and 6 months if irradiation is • or blood cell for should irradiated cellular blood components during and for d before the cell to prevent the collection of T which can 2 • All patients or blood cell should irradiated cellular blood components from of until 3 months months if irradiation was used in 2 TA-GvHD has been reported in all of disease et al, et al, et al, but in patients with where the risk is to and or disease There are reports of TA-GvHD in and the have been in patients with • All and with at any stage of the disease should have irradiated red cells and for 1 The purine analogues and with low which may for after There are case reports of TA-GvHD following of cell with et al, et al, and et al, The with newer purine and agents with as bendamustine to the of and the purine of and is evidence of safety it is to the use of irradiated components in patients receiving and other new purine analogues and related as alemtuzumab and rituximab are clinical use. case of TA-GvHD has been reported in the and a 2 of rituximab by alemtuzumab in et al, were but and were also of an related to be which in a patient who non-irradiated blood The and revised recommendations for alemtuzumab to irradiation of blood components circumstances dictate and is not as necessary with • with purine drugs and should irradiated blood components 1 • The with other purine and new or related as bendamustine and is but use of irradiated blood components is recommended as agents have a of Irradiated blood components should be used after alemtuzumab use after rituximab (anti-CD20) is not recommended at this new immunosuppressive drugs and biological agents are there is a need for regular review of 2 There are a case reports of TA-GvHD after and other routine in immunocompetent are given the of cases of TA-GvHD have been reported after of a of This is a the of dose of in and is and should be TA-GvHD following is et al, et al, and to from the Irradiated blood components are To no cases of TA-GvHD have been reported after the use of components in recipients with alemtuzumab has been used in it is to irradiate blood components in of the recognized with this agent in other patient is used for the of as and TA-GvHD is not reported in this it is to irradiate blood components in patients receiving this agent until more There are no reports of patients TA-GvHD the T cell • It is not necessary to irradiate blood components for patients routine with or after alemtuzumab has been used in the The of new of and clinical must to be 2 that irradiation of red cell and platelet transfusions before the risk of to and the risk of et al, committee on aplastic anaemia that irradiated blood components should be used in all patients with aplastic anaemia who are this is in in and the there is no clinical evidence to this and the routine use of blood components has the risk of in aplastic anaemia has been by the more immunosuppressive A of and that of irradiated blood components after et There was no consensus on to this The cases of in a patient with severe aplastic anaemia with and in a recipient who more than et al, Studies using alemtuzumab in aplastic anaemia are in et al, in irradiated blood components, the risk of TA-GvHD is with the BCSH on and of et al, the use of irradiated blood components in patients with aplastic anaemia with immunosuppressive therapy until evidence There is no evidence to the of of irradiated components, but the at until the lymphocyte is • of the from anti-thymocyte globulin to the more immunosuppressive use of irradiated blood components for aplastic anaemia patients receiving immunosuppressive therapy with 2 • a recommendation as to irradiated components should to be used after at risk of TA-GvHD should be made of their need for irradiated blood components and be provided with clear patient and for the case are from Blood and in and in and are in by the Blood 1 an of a of which is by the patient and the other of which should be to the of a patient in use. The have the need to of transfusion as irradiated components, by clinical and and in the of patients as a of blood transfused UK have or systems with and diagnostic that the transfusion to the of drugs (e.g. purine or the diagnosis of high risk as The of a national system, and part of the patient for and transfusion healthcare a to patient • at risk of TA-GvHD should be made of their need for irradiated blood components and be provided with appropriate and an for clinical the recommendations from to clinical and and of for transfusion, irradiated components. to and clinical systems with and diagnostic to should be and in of patients is a and the of a national system for and of transfusion is an to patient 2 it necessary to irradiate cellular blood components which are the of to any of irradiation if of the newer purine drugs and other related agents are to recipients to the and in are to be and at the time of to the the British Society for Haematology the any for the of the