Single-unit transfusions of RBC enzymatically converted from group B to group O to A and O normal volunteers

Abstract

Full-unit transfusions of RBC enzymatically converted from group B to group O by treatment with alpha-galactosidase (ECO RBC) to group O and A normal healthy individuals exhibit excellent in vivo survival times (24-hour survival 95.1% +/- 2.3%, T50 36.9 +/- 4.6 days). These results confirm our earlier findings describing ECO RBC in vitro viability and normal in vivo survival time after small-volume infusions. No significant increase in pretransfusion anti-B titer or score is observed in either group O or A subjects provided that sufficient enzyme is used to treat the cells: Cells transfused to group O recipients require higher levels of enzyme (185 to 200 U/mL RBC) than those infused to group A (90 U/mL RBC). Two separate single-unit transfusions of ECO RBC to one group O recipient (4.5 months apart) also survived normally (24-hour survival 96% and 92%, T50 40 and 36 days) and did not increase preexisting anti-B levels in this subject. ECO RBC were not agglutinated or lysed by recipient sera before or after transfusion. Similarly, no antibody development to the alpha- galactosidase used in cell treatment (and washed from the product before transfusion) could be detected in any subject. The sustained increase in hemoglobin levels after transfusion of ECO RBC suggests that this product will be useful in treatment of acute and chronic anemia.

Universal RBCs

“…Overall, the transfusions of ECO RBCs appeared safe and effective; there were no acute transfusion reactions or evidence of hemolysis, and chromium survival studies showed that the lifespans of the transfused ECO and group O RBCs were equal. However, a number of in vitro serologic abnormalities were noted, which were similar to observations in the previous studies of ECO RBC transfusions to normal volunteers 4,5 . Five of 19 patients who received ECO RBCs had significant increases in anti‐B titers, and 2 of these patients had incompatible antiglobulin crossmatches with ECO RBCs 7 .…”

“…Pioneering studies by the late Jack Goldstein and colleagues 3 at the New York Blood Center demonstrated that this process of enzymatic conversion of group B RBCs to group O could be carried out with the enzyme coffee bean α‐galactosidase under conditions that leave the RBCs physically and functionally intact and suitable for transfusion. Studies in group O or group A volunteer recipients showed that these enzymatically converted group O (ECO) cells functioned essentially identically to group O RBCs; there was no evidence of acute transfusion reactions or hemolysis, and RBC survival in the recipients was normal 4 . Multi‐unit or second transfusions were also well tolerated 5,6 .…”

“…Again, this is tremendously exciting progress, but the PEG RBC field is much newer and less advanced than the ECO RBC field. Collection of animal and, eventually, human data (comparable to those from studies of ECO RBCs 3–7 ) on the in vivo results of PEG RBC transfusions and monitoring for transfusion reactions, hemolysis, chromium survival studies, antibody formation (including antibodies to neo‐antigens created by the pegylation process), and other potential toxicities will have to be performed to find out if the initial promise of this research bears fruit.…”

Blood group A immunodeterminants on human red cells differ in biologic activity and sensitivity to alpha‐N‐acetylgalactosaminidase

“…In their studies of transfusions of enzyme-treated group B RBCs to allogeneic recipients, Lenny et al1*'4. 15 and Goldstein et a1.I6 treated group B RBCs with a coffee bean a-galactosidase at sufficiently high concentrations to abolish hemagglutination with B antisera within 2.5 hours of incubation. They demonstrated that RBCs so treated survived normally in blood group A and 0 recipients, including those receiving repeated transfusions of enzyme-treated group B RBCS.','~.…”

Elimination of blood group antigens: hope and reality

“…These studies demonstrated survival of ECO-RBCs in the blood stream and absence of the usual early clinical signs of haemolytic immune reaction. A few years later the same group reported transfusion of one to two full units (200-400 ml) of ECO-RBC with no particular side effects (Lenny et al, 1991(Lenny et al, , 1995. Kruskall et al (2000) reported a similar trial involving transfusion of two units of ECO-RBC in a cohort of 21 A patients presenting with various diseases [solid tumours, leukaemia, human immunodeficiency virus (HIV) infection].…”