Evaluation of extracorporeal alkylation of red cells as a potential
treatment for sickle cell anemia
S Charache, R Dreyer, I Zimmerman and CK Hsu
Nitrogen mustard and nor-nitrogen mustard inhibit sickling, but the
concentrations required would be associated with unacceptable toxicity if
these agents were administered to patients. Red cells could be treated
extracorporeally and infused back into donors, if the alkylating agent
could be removed or inactivated, if the treatment per se did not
significantly shorten red cell survival, and if viable alkylated
lymphocytes could be eliminated from the treated blood. To estimate whether
these conditions could be met in a clinical trial, red cells from four dogs
were alkylated at 6-wk intervals. No toxic reactions were observed,
although not all nor-nitrogen mustard was removed by the washing procedure.
Red cell survival was shortened to about half that of control cells, using
concentrations of alkylating agent which reduce sickling by 50%.
Lymphocytes from treated blood could still exclude trypan blue, but could
not be shown to circulate after reinfusion into donor dogs. If alkylating
agents are used to treat patients' cells, inhibition of sickling may
outweigh the shortening of red cell life span induced by the treatment;
blood should probably be irradiated before infusion to avoid administration
of alkylated and potentially mutated, but viable, lymphocytes.
Volume 47,
Issue 3,
pp. 481-488,
03/01/1976
Copyright © 1976 by The American Society of Hematology
