IL-2 has been used after autologous BMT (ABMT) with the aim of inducing graft versus
leukemia (GVL) effect. Our studies in mice have shown that
IL-2 therapy induces GVL effect when employed after BMT with bone marrow (BM) that has been activated with
IL-2 in vitro (ABM). The present study was carried out to define the time of optimal GVL effect after BMT so that the immunomodulatory approaches could be concentrated at the time of maximum GVL effect. Our data show that GVL effect was induced if
IL-2 was instituted immediately after BMT with ABM in mice with
acute myeloid leukemia; institution of
IL-2 1 week after BMT with ABM did not induce GVL effect.
IL-2 therapy instituted immediately or 1 week after BMT with fresh bone marrow (FBM) did not induce any GVL effect. A significant increase in the NK activity was noticed whether
IL-2 was instituted immediately or 1 week after BMT, either with FBM or with ABM. To evaluate the ability of
IL-2 in the eradication of residual disease from the autograft and the host, BM with variable infiltration with
leukemia was activated with
IL-2 and used for BMT in leukemic mice. The GVL effect of BM with minimal
leukemic infiltration (absence of morphologically demonstrable disease) was comparable to the GVL effect of normal BM. These findings suggest that: (a) maximum GVL effect after BMT with ABM is concentrated in the early post-transplant period possibly because of
minimal residual disease during this time; (b) an increase in the NK activity induced by
IL-2 therapy may not predict for an improved GVL effect; and (c) for optimum GVL effect, BM with minimal
leukemic infiltration should be activated with
IL-2 before BMT.