Graft-vs-leukemia and moderation of graft-vs-host reaction in transplantation therapy of viral leukemia.

In transplantation studies of Rauscher leukemic SJL/J mice longer median survival times (MST) were obtained with spleen cells from syngeneic donors than with marrow. These could be further extended by immunization of the donors to Rauscher virus (RLV) and Rauscher leukemia cells. This suggests that spleen cells exert a greater graft-vs-leukemia effect than marrow. Nevertheless, with syngeneic cells all recipients eventually died of leukemia relapse. In contrast, the use of RLV-resistant C57BL/10J allogeneic marrow cells resulted in a substantial number of long-term survivors and a low incidence of GvH disease, while the use of pure allogeneic spleen cells resulted in early and fatal GvH response in all recipients. To determine if allogeneic spleen cells might have any demonstrably beneficial effect on survival of leukemic mice various small quantities of C57BL/10J spleen cells were mixed with marrow from the same donors and engrafted into normal and leukemic SJL/J recipients. Among the normal mice MST decreased as a function of spleen cell concentration. However, with the leukemics the use of 2.5 or 5% spleen cells resulted in later deaths than that found when leukemic mice were given only marrow. Also, for all allogeneic spleen/marrow mixtures tested, survival of leukemic recipients exceeded that of normal recipients given the same cell mixtures. These data suggest a possible beneficial effect of small amounts of allogeneic spleen cells in transplantation therapy for leukemia, and a possible competitive interaction of anti-host and anti-leukemic activities of the transplanted cells leading to a moderation of the GvH response.