Protection against Transfusion-Associated Graft-versus-Host Disease in Blood Transfusion: Is Gamma-Irradiation the Only Answer?

Abstract

Transfusion-associated graft-versus-host disease (TA-GvHD) is an infrequent, but fatal, complication associated with transfusion of any cellular blood component. At present, gamma-irradiation of cellular blood components is the only acceptable method for preventing TA-GvHD. All blood components can be subjected to gamma-irradiation, which irreversibly inactivates leukocytes, especially T lymphocytes, while preserving the functional integrity of the pharmaceutically effective cellular blood components. Pathogen inactivation technologies have been developed to eliminate the minimal transfusion-associated risks caused by viral or bacterial contaminants. The INTERCEPT™ Blood System for platelets is based on the use of amotosalen HCl and UVA-irradiation. It sufficiently inhibits the replication of parasitic, bacterial, and viral genomes and inactivates T cell replication and cytokine generation on at least an equivalent level to gamma-irradiation. The INTERCEPT Blood System for platelets shows great robustness in inactivating viable T lymphocytes with more than a 5 log₁₀ reduction in platelet concentrates, and it may have the potential to replace gamma-irradiation of platelet concentrates.

Transfusion of 7‐day‐old amotosalen photochemically treated buffy‐coat platelets to patients with thrombocytopenia: a pilot study

“…[13][14][15][16] The PCT process also inactivates contaminating white blood cells, including T lymphocytes, which cause transfusion-associated graftversus-host disease (TA-GVHD) and may contribute to febrile nonhemolytic transfusion reactions. [17][18][19][20] Clinical trials performed to date have demonstrated the therapeutic efficacy and safety of PCT PLTs to increase PLT counts and to prevent and control bleeding in patients with thrombocytopenia. [21][22][23] Because the PCT system for PLTs has demonstrated robust inactivation of Gram-negative and Gram-positive (including anaerobic) bacteria at levels far in excess of those observed at time of collection, 13,14 the prolonged PLT storage with reduced risk of transfusion-associated bacteremia merits consideration.…”

“…This photochemical treatment (PCT) system uses a combination of amotosalen and ultraviolet A (UVA) light 11,12 to inactivate a broad range of contaminating pathogens, including bacteria, viruses, and protozoa in PLTs 13‐16 . The PCT process also inactivates contaminating white blood cells, including T lymphocytes, which cause transfusion‐associated graft‐versus‐host disease (TA‐GVHD) and may contribute to febrile nonhemolytic transfusion reactions 17‐20 …”

Quantification of Viral Inactivation by Photochemical Treatment with Amotosalen and UV A Light, Using a Novel Polymerase Chain Reaction Inhibition Method with Preamplification

“…The inactivation mechanism combines the nucleic acid-intercalating property of amotosalen with its cross-linking capabilities after UVA activation to eliminate the replicative function of treated pathogens. PCT has been shown to inactivate a broad spectrum of viruses, bacteria, parasites, and white blood cells and create safer blood-transfusion products [11,12,[14][15][16][17][18][19][20].…”

Preparation and Pathogen Inactivation of Double Dose Buffy Coat Platelet Products using the INTERCEPT Blood System

“…7,8 It can also provide an alternative to redundant safety measures such as bacterial detection 9 and gamma irradiation. [10][11][12] In addition, INTERCEPT allows us to treat double dose platelet units which benefits our production efficiency and helps us adhere to our budgets.…”