Transfusion‐associated graft‐versus‐host disease reexamined: potential for improved prevention using a universally applied intervention

Abstract

BACKGROUND Transfusion‐associated graft‐versus‐host disease (TA‐GVHD) is a rare, often fatal complication of blood transfusion that can occur in immunocompromised or immunocompetent recipients and is the result of viable T cells present in the blood components transfused. STUDY DESIGN AND METHODS We examined the TA‐GVHD clinical case literature including numerous original clinical case reports and several comprehensive case series. We also evaluated recent in vitro experimental data on the inhibition of T cell proliferation, comparing the effect of a specific pathogen inactivation (PI) technology to that of the Food and Drug Administration–recommended gamma irradiation dose of 2500 cGy. RESULTS We identified 12 published TA‐GVHD cases with atypical/milder or delayed symptom presentations and/or an atypical clinical course; these included cases attributed to leukoreduced or suboptimally irradiated units. We summarize recent in vitro data using a sensitive limiting dilution assay that establish that, compared to irradiation at the recommended 2500 cGy dose, PI using amotosalen/ultraviolet A, or amustaline/glutathione achieves a greater degree of inhibition of T cell proliferation. CONCLUSION We propose that TA‐GVHD has a spectrum of disease severity indicating that additional mild cases may still occur but be undiagnosed and/or underreported, opening up the possibility, supported by in vitro experimental data, that irradiation at the currently established dose may not be fully protective. Furthermore, since many US institutions use component irradiation selectively only for immunocompromised patients, immunocompetent recipients are not fully protected. PI technologies appear to be at least equal to, if not better than, gamma irradiation in abrogating the ability of T cells to proliferate, and if applied to all blood components, protection against TA‐GVHD would be an additional benefit that would allow for the elimination of component irradiation.

Inactivation of a broad spectrum of viruses and parasites by photochemical treatment of plasma and platelets using amotosalen and ultraviolet A light

“…While this review focused on the inactivation of viruses and parasites, the amotosalen/UVA PRT has proven efficacy to prevent transfusion‐associated graft‐versus‐host disease and bacterial TTIs, the most significant infectious risk in transfusion today . PRT is now considered an alternative to bacterial screening, irradiation, and CMV testing .…”

Double-filtered leukoreduction as a method for risk reduction of transfusion-associated graft-versus-host disease

“…Our studies indicate that the first round of filtration results in a 5 log reduction, and the following round is indicative of a further 3 log reduction. In contrast, gamma irradiation showed that the inactivation level of T cells resulted in a range of 3-6 log reduction [7]. Pathogen inactivation methods provided better rate of inactivation, being 6.2 log for amotosalen/UVA [39], 5.9 log for amustaline/GSH [7] or 4.7-6.5 for riboflavin/UV [20,40].…”

“…Removal of these cells before transfusion has been proposed to reduce the incidence of TA-GvHD, but reports of TA-GvHD after transfusion of leukoreduced blood components can be found in the literature [2][3][4]. Despite these reports being from many years ago, leukoreduction by filtration is generally not accepted as a method to sufficiently to prevent TA-GvHD [5,6] Irradiation disables T cells' mitotic capabilities and is currently the de facto golden standard method for full prevention of TA-GvHD, despite some incidences of TA-GvHD being reported after irradiation [7].…”

“…An investigation on whether a method is suitable to fully prevent whether it can fully prevent TA-GvHD is not possible; even the current method of gamma-ray irradiation has not been subject to any randomized clinical trial on this matter [7]. We relied on investigating the level of leukocytes left after two rounds of filtration, and compared that with data on the level of mononuclear cells required to show proliferation in vitro, or GvHD symtomes in vivo.…”

The Evolution of Blood Transfusion in the Trauma Patient: Whole Blood Has Come Full Circle

“…Transfusion of nonleukoreduced blood products does carry risks including the rare but lethal complication of transfusionassociated graft versus host disease. 66,67 A 2015 review by Kopolovic et al found 348 all-time reported cases of graftversus-host disease. Conversely, there were over 200,000 trauma fatalities in 2017 in the United States alone, 68 and trauma patients receiving a blood transfusion have an odds ratio of mortality of 3.35 compared with those who do not receive a transfusion.…”