MULTIPLE-UNIT AND 2ND TRANSFUSIONS OF RED-CELLS ENZYMATICALLY CONVERTED FROM GROUP-B TO GROUP-O - REPORT ON THE END OF PHASE-1 TRIALS

Background: It has previously been shown that 1 and 2 units (200-400 m L) of red cells (RBCs) enzymatically converted from group B to group O by treatment with alpha-galactosidase (EGO RBCs) are safe and efficac ious when transfused to normal group O or A persons. Study Design and Methods: The current report describes studies in which 1) normal group A and O subjects received large volumes of these cells (3 units), 2) some group O subjects underwent transfusion several months later, and 3) ECO RBCs were prepared by the use of recombinant coffee bean alpha- galactosidase and transfused to a group O subject, to demonstrate the in vivo equivalence of ECO RBCs, whether prepared with native or recom binant alpha-galactosidase. Results: Clinical evaluation (hematologic tests, chemistry analysis, urinalysis) and serologic analyses did not reveal any evidence of subtle or acute transfusion reaction or signifi cant increase in preexisting anti-B titer. ECO RBC survival within the circulation of the recipients was normal (24-hour survival, 95.5 +/- 0.9%; t1/2, 34.7 +/- 6.1 days; n = 8 transfusions), and the efficacy o f the transfusions was manifested in elevations in recipient hemoglobi n and hematocrit (hemoglobin increase, 1.5 +/- 0.6 g/dL; hematocrit in crease, 3.6 +/- 1.6%; n = 8 transfusions). Conclusion: ECO RBCs are sa fe and efficacious when transfused more than once or in multiple-unit volumes to group O or A subjects, and ECO RBCs prepared with recombina nt or native enzyme are equivalent in vivo.