The Antigenicity of Normal and Leukemic Human Leukocytes

1. A leukoagglutinin was formed in the serum of a normal human subject who received 10 intravenous injections of blood from a single patient with chronic myelogenous leukemia over a period of 20 weeks. 2. Coincident with development of the leukoagglutinin, first detectable one week after the fifth injection of leukemic blood, the normal subject experienced progressively more severe febrile reactions to the infusions and exhibited a characteristic pattern of leukocyte response—namely, an immediate transient leukopenia, followed by a leukocytosis which reached its peak around 3 hours and subsided to normal within 12 hours. 3. During the early part of the investigation immature leukocytes, presumably from the leukemic donor, could be identified in the recipient’s circulation during the first hour immediately following injection, but none could be found following the tenth infusion of leukemic blood. 4. The leukoagglutinin which appeared in response to the injections of blood from the single leukemic donor was a typical iso-antibody, showing a broad pattern of reactivity against normal leukocytes from 127 of 129 donors, leukemic leukocytes from 5 of 5 patients with chronic myelocytic leukemia and 6 of 6 patients with chronic lymphocytic leukemia. No reactivity was observed against the recipient’s own leukocytes, and little or no reactivity was demonstrable against the immature leukocytes from 3 patients with acute leukemia. 5. Eighteen months after the last injection of leukemic blood, restimulation of a leukocyte iso-agglutinin in the previously immunized recipient was provoked within one week of commencing a series of intravenous infusions of blood from a single normal donor. 6. The volume of normal leukocytes employed for the restimulation was 1/10 to 1/100 the volume of leukemic leukocytes employed for the primary immunization. 7. The concept of antibody excess was demonstrable in the sensitized recipient. No evidence of in vivo absorption of leukoagglutinin activity was observed after transfusion of 500 ml. of blood from the normal donor. The severity of the recipient’s reaction to the transfused blood was clearly related to the dose of donor leukocytes administered, 0.47 billion cells causing no reaction but 4.16 billion causing a moderately severe reaction. 8. Fifteen months after completion of the injections of normal blood, reexposure of the normal subject to injections of blood from a second leukemic donor resulted in prompt restimulation of leukoagglutinin activity in the recipient’s serum. 9. The leukoagglutinin could be completely absorbed in vitro by incubation with donor leukocytes. 10. The leukoagglutinin was concentrated in the gamma globulin fraction of the recipient’s plasma. 11. The recipient exhibited typical symptomatic reactions and transient hematologic changes following the infusions of leukemic blood. 12. It was possible to correlate the severity of the recipient’s clinical reactions both with the strength of the recipient’s leukoagglutinin, as well as with the dose of donor leukocytes transfused. 13. Serologic observations, plus the results of fractionated transfusion studies, indicated that the recipient’s transfusion reactions were related to sensitivity to the donor’s buffy coat (Part II), and more specificially to donor leukocytes (Part III), rather than to donor plasma, platelets or erythrocytes. 14. Sustained stimulation of the recipient’s white cell count as a result of the injections of leukemic blood was not observed. 15. There has thus far been no evidence of transmission of leukemia to the recipient (now 6½ years after the first course of injections of leukemic blood and 2 years since completion of the present study).