INTERLEUKIN-3 PRIMING IN ACUTE MYELOID-LEUKEMIA PATIENTS

Several studies have demonstrated that G-CSP, GM-CSF and, in particula r, IL-3 can effectively recruit acute myeloid leukaemia (AML) blasts i nto the cell cycle, resulting in a significant increase in cytosine-ar abinoside (Ara-C) mediated cytotoxicity in vitro. Since IL-3 has shown biological and clinical activity, we investigated the cell kinetic ef fects of rIL-3 and high-dose Ara-C/idarubicin in three patients with r efractory AML selected for the presence of chromosome 7 monosomy; this enabled differentiation between the effects of IL-3 on leukaemic and on normal cells. The in vivo administration of rhIL-3 (250 mu g/m(2) d s.c. for 6-10 d) recruited AML blasts into the cell cycle in two of t he three patients, and this effect resulted in an increase in in vitro growth of clonogenic cells (CFU-L) and of their S-phase fraction. The percentage of leukaemic cells with monosomy 7 increased only in the t wo cases who showed a proliferative response. Normal cells were not re cruited, even when rhIL-3 was administered for up to 10 d. In vitro st udies showed an increased Ara-C cytotoxicity on clonogenic AML cells, in particular with IL-3 plus GM-CSF, thus confirming the priming effec ts of IL-3 in the two responding cases. The results of this study sugg est that rhIL-3 can selectively recruit leukaemic cells into the cell cycle. Although leukaemic blasts can be sensitized to Ara-C, other mec hanisms of primary blast resistance may limit the clinical benefit of kinetic-based approaches.