Time pattern of the antileukemic effect of graft-versus-host reaction in mice.

Inbred mice were inoculated with transplantable leukemia. X-irradiated, and given injections of bone marrow and spleen cells from allogeneic donors. Control animals received syngeneic cells after irradiation. On Days 1 to 7 after this treatment, the mice were individually tested for the presence of leukemic cells by transferring from each the spleen, a piece of liver, left kidney, left lung, blood, and bone marrow into syngeneic assay mice. The organs and tissues of mice treated with allogeneic cells were able to transfer leukemia to the assay animals only if removed 1 to 4 days after irradiation and injection of allogeneic cells. With organs and tissues removed on days 4 to 6, the incidence of positive transfers sharply decreased, and on Day 7 the leukemic cells could not be detected in any of the organs and tissues tested. The data are consistent with the view that the acute graft-versws-host reaction destroys leukemic cells before an irreparable damage is inflicted to the host. In additional experiments, cyclophosphamide was used to modify the graft-versus-host reaction. Various treatment schedules suppressed the graft-vmws-host reaction to a comparable degree yet differed in the ability to leave unharmed the antileukemic effect of the reaction. If the drug was given in small daily doses starting 4 days after irradiation and injection of allogeneic cells, the reaction was well controlled, and relapses of leukemia were avoided.