Risks associated with red blood cell transfusions: potential benefits from application of pathogen inactivation

Kleinman, Steve; Stassinopoulos, Adonis

RBC quality during storage has been summarized in the literature. 104, 105, 110, 111 PI studies are ongoing by both PI manufacturers; available data are summarized in Table 7 . 77, 78, 99, 104, 105, [112] [113] [114] [115] [116] [117] [118] [119] [120] [121] These inactivation data still need to be validated by full-unit studies with multiple replicates, and hence care should be taken in their interpretation; nevertheless, a few points emerge. For the S-303 and GSH system, the extent of PI has remained comparable between the first-and second-generation approaches. For the riboflavin and UV system, the limited data indicate that inactivation of some pathogens is lower in the WB system than in the PLT and plasma systems, despite the higher dose of UV light used (80 J/mL RBC vs. 6.2 J/mL PLASMA ). This is consistent with the lower efficiency for UV light delivery in the presence of hemoglobin (Hb)-containing RBCs. 99 Each technology has undergone recovery and survival studies independently performed by the same investigator (Table 8) . 122, 123 The S-303 and GSH system was tested in 27 healthy volunteers in two centers using a crossover design. 122 At 35 days of storage, the 24-hour recovery of autologous treated RBCs compared favorably with control RBCs (88% vs. 90%, p 5 0.31), meeting FDA requirements. The survival of S-303 RBC (T 50 ) was lower than that of control RBCs, but within the normal range (32.7 days vs. 39.5 days; p 5 0.0001; normal, 28-35 days). 122 In a different study, 123 RBCs stored for 42 days were manufactured from riboflavin and UV-treated autologous WB units prepared using variable UV doses (22, 33 , and 44 J/mL RBC ). Only five of 11 subjects met the FDA requirement of more than 75% recovery at 24 hours; mean RBC survival was 24 6 9 days. There was a trend toward lower recovery and lower survival for higher illumination doses. These data, along with recently published in vitro data at Storage Days 21 and 42, indicate that a storage time shorter than 42 days will be required for an 80 J/mL RBC dose. 111 Table 8 122-131 also reports other Phase II and III studies, primarily using information from the ClinicalTrials.gov website. [124] [125] [126] [127] [128] [129] [130] [131] For the first-generation S-303 and GSH system, a Phase III trial in SCD patients was terminated early when two patients developed apparent RBC antibodies, but no sequela. 108 The companion Phase III first-generation PI-RBC study in cardiovascular surgery patients with acute anemia, conducted simultaneously with the SCD study, met its primary noninferiority composite endpoint despite its early termination due to the SCD study findings. 124 After S-303 reformulation, two Phase III clinical studies with the second-generation S-303 and GSH RBC system are in progress in Europe, targeting the indications of acute and chronic anemia in cardiovascular patients and patients with thalassemia, respectively. 125, 127 * Inactivation achieved with first-generation system (0.2/2 mmol/L GSH). †These data are from low-titer experiments and inactivation of higher bacterial titers was not evaluated. For riboflavin and UV, an additional Phase II study (presumably using an 80 J/mL RBC dose) has finished recruiting. 129 A Phase III study on the prevention of TTmalaria among recipients of PI-WB is under way in Africa. 130