The Antigenicity of Normal and Leukemic Human Leukocytes

1. A leukoagglutinin was formed in the serum of a normal human subjectwho received 10 intravenous injections of blood from a single patient withchronic myelogenous leukemia over a period of 20 weeks.

2. Coincident with development of the leukoagglutinin, first detectable oneweek after the fifth injection of leukemic blood, the normal subject experiencedprogressively more severe febrile reactions to the infusions and exhibited acharacteristic pattern of leukocyte response—namely, an immediate transientleukopenia, followed by a leukocytosis which reached its peak around 3 hoursand 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 circulationduring the first hour immediately following injection, but none could befound following the tenth infusion of leukemic blood.

4. The leukoagglutinin which appeared in response to the injections of bloodfrom the single leukemic donor was a typical iso-antibody, showing a broadpattern of reactivity against normal leukocytes from 127 of 129 donors, leukemicleukocytes from 5 of 5 patients with chronic myelocytic leukemia and 6 of 6patients with chronic lymphocytic leukemia. No reactivity was observed againstthe recipient’s own leukocytes, and little or no reactivity was demonstrableagainst the immature leukocytes from 3 patients with acute leukemia.

5. Eighteen months after the last injection of leukemic blood, restimulationof a leukocyte iso-agglutinin in the previously immunized recipient was provoked within one week of commencing a series of intravenous infusions ofblood from a single normal donor.

6. The volume of normal leukocytes employed for the restimulation was 1/10to 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 observedafter transfusion of 500 ml. of blood from the normal donor. The severity ofthe recipient’s reaction to the transfused blood was clearly related to the doseof donor leukocytes administered, 0.47 billion cells causing no reaction but4.16 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 leukemicdonor resulted in prompt restimulation of leukoagglutinin activity in therecipient’s serum.

9. The leukoagglutinin could be completely absorbed in vitro by incubationwith donor leukocytes.

10. The leukoagglutinin was concentrated in the gamma globulin fraction ofthe 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 reactionsboth with the strength of the recipient’s leukoagglutinin, as well as with thedose of donor leukocytes transfused.

13. Serologic observations, plus the results of fractionated transfusion studies,indicated that the recipient’s transfusion reactions were related to sensitivityto 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 theinjections of leukemic blood was not observed.

15. There has thus far been no evidence of transmission of leukemia to therecipient (now 6 years after the first course of injections of leukemic bloodand 2 years since completion of the present study).

Submitted on July 15, 1960 Accepted on November 20, 1960