Production of pathogen-inactivated RBC concentrates using PEN110 chemistry: a Phase I clinical study.

BACKGROUND

Despite extensive reductions in risk, donor selection and testing cannot eliminate pathogen transmission. The objective of this study was to evaluate clinically the viability of pathogen-inactivated RBCs.

STUDY DESIGN AND METHODS

Twelve healthy subjects each donated two units of blood that were handled as additive system control units or were inactivated using the PEN110 process (INACTINE, V.I. Technologies) in randomized order. PEN110, which inactivates pathogens by reacting with nucleic acid bases, was incubated with RBCs for 6 hours, followed by washing and quenching with sodium thiosulfate. Radiolabeled RBC recovery and survival determinations were undertaken after 28 days of storage; biochemical and hematologic variables were assessed over 42 days.

RESULTS

After 28 days, treated units had a 24-hour double-label ((51)Cr/(99m)Tc) recovery (85.0 +/- 5.0%) that was indistinguishable from control units (85.9 +/- 2.7%); the times required for reduction of radioactivity of labeled cells to half the Day 1 activity (T(50)) were similar for both groups (treated, 31.9 +/- 8.2 days; control, 32.9 +/- 3.3 days). No deleterious effects of PEN110 treatment were found on RBC antigens tested. Treatment reduced 2,3-DPG levels by half and slightly lowered pH levels. Throughout the 42-day storage period, treated RBCs had a lower level of lactate production and a trend toward lower glucose consumption. Hemolysis remained below 1 percent; supernatant potassium and ATP levels were lower than those seen in control RBCs.

CONCLUSION

PEN110-treated RBCs stored for 28 days meet all critical requirements for therapeutically useful units.