Safety Profile of Platelet Components Treated with Amotosalen-UVA Pathogen Inactivation Transfused in Routine Use: Multi-Year Active Hemovigilance.

Pathogen inactivation (PI) of platelet components (PC) with amotosalen and UVA light (INTERCEPT Blood System™, Cerus Europe BV, Amersfoort, Netherlands) has been implemented in routine use in > 100 European blood centers. Active hemovigilance (HV) data were utilized to characterize the adverse event (AE) profile in a broad spectrum of patients with specific focus on respiratory safety.

Two, non-overlapping, HV programs which monitored the response to all transfusion of PC for 24 hours after each transfusion in routine were used to compute the frequencies of allergic reactions, transfusion-associated cardiac overload (TACO), transfusion-related acute lung injury (TRALI), and signs and symptoms of respiratory distress. Data from the Agence National de Securité du Médicament et des Produits de Santé (ANSM, Paris, France) were used to compare the safety of conventional (C) and PI PC for allergic AE, TACO, and TRALI for all patients in France. Data from the Cerus HV program were used to estimate the frequencies of all respiratory signs and symptoms including TRALI and TACO in multiple clinical centers outside of France. In both programs, AE clinical severity was classified as: Grade 1 =non-severe no clinical intervention, Grade 2 = severe requiring intervention, Grade 3 = imminently life threatening, and Grade 4 = death. The relationship of the AE to PC transfusion was classified as: 0 = excluded, 1 = possible, 2 = probable, and 3 = certain. TRALI and TACO were defined using established criteria (Toy et al Blood 119:1757, 2011) in which TRALI and TACO differed only by the presence of left atrial hypertension, or fluid overload, or congestive heart failure. AE of all severity grades and any level of imputed relation were included.

Starting in 2009, ANSM specifically identified data for PI-PC and C- PC (Table 1). Using ANSM annual HV reports, data were reviewed for 776,401 C-PC and 66,843 PI-PC transfused. From 2009 to 2011 the use of platelet additive solution (PAS) to decrease the plasma protein content of PC increased from 47.8% to 86.1% of transfused PC, and the proportion of whole blood derived pooled buffy coat PC increased from 28.1% to 48.6%. In parallel with these changes, the frequency of allergic reactions, TACO, and TRALI declined from 2009 to 2011(Table 1). The frequency of TACO and TRALI per 10⁴ PC transfused reported by ANSM was compared for C-PC and PI-PC (Table 2). The frequencies of TRALI and TACO declined from 2009 to 2011 for conventional PC and were very low for PI-PC, although smaller numbers of PI-PC were transfused. A second active HV program (Cerus HV) used a protocol similar to the ANSM protocol specifically to monitor allergic AE and all respiratory AE of all grades, including both signs and symptoms, in 4,067 patients transfused with 19,175 PC in 22 clinical centers (Table 3). In contrast to the ANSM program that included all patients in France, the Cerus HV program was predominantly populated by repeatedly transfused hematology-oncology patients. The number of respiratory AE imputed to PC transfusion was increased compared to the ANSM HV program due to reporting of all respiratory signs and symptoms as AE, but no TRALI or TACO were imputed to transfusion of PI-PC.

Two non-overlapping active HV programs were sensitive for detection of allergic and respiratory AE including TRALI and TACO. The increased use of PAS and pooled whole derived PC paralleled a decreased frequency of AE imputed to PC transfusion. Consistent with previous observations (Corash et al Blood 117:1014, 2011) transfusion of PI-PC was not associated with an increased frequency of TRALI or TACO.

Corash:Cerus Corporation: Employment, Equity Ownership.