Prevention of transfusion‐associated graft‐versus‐host disease with pathogen‐reduced platelets with amotosalen and ultraviolet A light: a review

Abstract

Background and Objectives Transfusion-associated graft-versus-host disease (TA-GVHD) is a serious complication of blood component transfusion therapy, caused by donor T lymphocytes. c-Irradiation or pathogen inactivation methods, capable of inactivating proliferating T cells in blood components, should be selected to prevent TA-GVHD. This review summarizes the published evidence to support the use of pathogen-reduced platelets with amotosalen (150 lM) and ultraviolet A light (UVA, 320-400 nm, 3 J/cm 2 ) for preventing TA-GVHD. Materials and MethodsAvailable literature on the use of pathogen-reduced platelets to prevent TA-GVHD was reviewed.Results Observational studies, animal models, in vitro studies and mechanistic studies of pathogen-reduced platelets with amotosalen and UVA light showed that inactivation of T cells are equal or even superior to c-irradiation.Conclusion Pathogen-reduced platelets with amotosalen and UVA light can be used as a measure to prevent TA-GVHD.Key words: pathogen-reduced platelets, platelet transfusion, TA-GVHD. IntroductionThe clinical course of allogeneic hematopoietic progenitor cell (HPC) transplantation is complicated by graft-versushost disease (GVHD). This condition results when donor T lymphocytes recognize the human leucocyte antigens (HLA) of the recipient as foreign, generating a characteristic immune response [1]. However, GVHD may also result as a complication of blood component transfusion because of the infusion of viable lymphocytes within cellular blood components [2]. Transfusion-associated graft-versus-host disease (TA-GHVD) is a lethal, although rare, complication of blood component transfusion. Three prerequisites are necessary to develop this complication of blood transfusion: (1) differences in histocompatibility between recipient and donor; (2) presence of immunocompetent T cells in the blood component; and (3) inability of the recipient to reject the immunocompetent cells [2].The clinical picture of TA-GVHD typically appears 8-10 days after transfusion. As seen in GVHD after allogeneic HPC transplantation, a characteristic cutaneous eruption appears, in association with watery diarrhoea, liver function test abnormalities and fever. The development of marrow aplasia with pancytopenia distinguishes TA-GVHD from GVHD occurring after allogeneic HPC transplantation [3]. According to criteria devised by the National Health and Safety Network (NHSN), the diagnosis of TA-GVHD is based on a combination of characteristic clinical findings and a tissue biopsy consistent with GVHD, with imputability established via the demonstration of leucocyte chimerism, specifically donor T lymphocytes in recipient tissue [4].Treatment of TA-GVHD is only rarely effective, and the prognosis of the disease is almost uniformly fatal [5]. Thus prevention of TA-GVHD in patients groups at risk is critical. These groups of patients are identified based on case reports and small case series published in the This is an open access article under the terms of the Creative Commons Attribution-Non...

Amotosalen/UVA treatment inactivates T cells more effectively than the recommended gamma dose for prevention of transfusion‐associated graft‐versus‐host disease

“…Routine use of the technology since then has resulted in no reported cases of TA-GVHD associated with the transfusion of INTERCEPT-treated platelet (or plasma) components after transfusion of 400,000 components under direct observation through hemovigilance studies or national hemovigilance systems, and no reports to the manufacturer on the transfusion of more than 1.5 million components manufactured for transfusion since the approval of the system for use in lieu of gamma irradiation. 39 This experience was consistent with clinical and postmarketing trial experience where amotosalen/UVAtreated platelet components were used for patient populations at risk. 40,41 After consideration of the system routine performance and the data above, AABB standards have included the use of amotosalen/UVA as an alternative to gamma since 2015 in the United States.…”

“…37,38 Analysis in previously reported LDA studies showed effective inactivation of T cells to the LOD at more than 5.39 6 0.29 log, 25 and the inactivation of the T cells was further found to be below the LOD, even when the doses of the amotosalen and UVA were reduced by a combined 3000-fold, indicating that at least a 3000fold level of safety exists for the treatment of blood components for the complete inactivation of T cells. 25,30,39 An established parent-to-F1 mouse transfusion model of TA-GVHD was used to show that treatment of splenocytes with amotosalen/UVA prevents TA-GVHD, in a manner similar to a gamma irradiation treatment control and unlike the untreated positive control. 32 In the same study, inactivation of the T cells with amotosalen/ UVA showed inactivation by LDA to the LOD, establishing a correlation between prevention of clinical TA-GVHD and reduction of the T-cell viability below the LOD.…”

Hypersensitivity transfusion reactions to platelet concentrate: a retrospective analysis of the French hemovigilance network

“…As the Amotosalen/UVA pathogen reduction method targets nucleated leukocytes, it is also effective at preventing transfusion‐related graft‐versus‐host disease . Therefore, Amotosalen/UVA‐treated PCs do not require gamma‐irradiation.…”

How do you… decide which platelet bacterial risk mitigation strategy to select for your hospital‐based transfusion service?

“…Additionally, irradiation is not required to prevent transfusion‐associated graft‐versus‐host disease (TA GVHD) for platelets that have undergone PR . However, for transfusion services that irradiate their own blood products, an irradiator would still be required for red blood cells.…”