Theoretically, leukoreduction (also known as leukodepletion or leukofiltration) could remove a sufficient number of white blood cells to limit TAGVHD; however, there have been 23 reported cases of TA-GVHD after transfusion of leukoreduced red blood cells in the literature, (39) indicating leukoreduction alone is not adequate to prevent TA-GVHD.
Interestingly, per the US Food and Drug Administration, from 2005 to 2015 there have been only 3 reported cases of death caused by TA-GVHD (1 case each in 2005, 2010, and 2011) in the United States.
A 2015 systematic review from 6 databases (Medline, Embase, the Cochrane library, Web of Science, British Medical Journal case reports, and the International Society of Blood Transfusion proceedings) identified 348 unique cases in the medical literature of TA-GVHD and found that 34.8% of the cases occurred in recipients who would warrant blood component irradiation based on underlying diagnosis.
Future studies should be conducted on this topic, which might require a generalized approach to blood product irradiation using the newer guidelines, or alternatives (as discussed below) that may help to mitigate TA-GVHD risks.
(42,43) In January 2016, the US Food and Drug Administration approved the use of the INTERCEPT Blood System (Cerus Corp, Concord, California) in the United States for apheresis platelets in order to reduce the risk of TA-GVHD using amotosalen plus UVA in place of irradiation.
Riboflavin plus UVA/UVB treatment by the Mirasol System (Terumo BCT Inc, Lakewood, Colorado) of whole blood was shown to be effective in both in vitro and in vivo studies (4.7-log reduction of viable T cells by limiting dilution assay) for the prevention of TA-GVHD and provided an alternative modality for the irradiation procedure for platelet and red blood cell products mutually.
For some conditions where irradiation of cellular blood product is widely considered required in order to prevent TA-GVHD, there were improvements between 1989 and 2014.
Despite recognition of some of the underlying risks predisposing patients to TA-GVHD, rare cases of TA-GVHD continue to be reported, simply based on the chance that a random blood donor will share enough similarity in HLA type that the recipient will fail to recognize the donor lymphocytes as foreign (thus allowing them to proliferate and attack the host).
To the extent that this is the case, respondents' lack of familiarity with their own institutions' indications for irradiation of cellular blood products cannot be excluded as contributors to the unexpectedly low rates of irradiation for conditions or circumstances widely thought to put patients at risk for developing TA-GVHD. Importantly, there are differences in the 2 irradiation practice surveys performed approximately 25 years apart.
Although some strides have been made, a surprising number of organizations do not currently irradiate cellular blood product for groups considered to be at risk for the development of TA-GVHD. Unexpectedly, for some at-risk groups fewer organizations required irradiation in 2014 when compared with 1989.
As understanding of the populations at risk for TA-GVHD evolves, new recommendations aimed at targeting the most vulnerable patients may be in order.
A systematic review of transfusion-associated graft versus host disease (TA-GVHD).