Histamine dihydrochloride and interleukin-2 in the treatment of acute myeloid leukemia.

Despite successful chemotherapeutic remission induction, most patients with acute myeloid leukemia still are destined to die from recurrent and refractory disease. Strategies to prolong remission and improve survival include high-dose chemotherapy, autologous or allogeneic stem cell transplantation, and other immunotherapeutic approaches. The focus on interleukin-2 (IL-2) has arisen from in vitro demonstration of enhancement of tumor-specific cytotoxic T-lymphocyte and natural killer-cell activity after cytokine activation. The local secretion of inhibitory substances and oxidative stress by monocyte/macrophage populations may inhibit the cytotoxic capacity of these effector cells. Recently, agents capable of modulating cytotoxic effector function have been identified, including histamine dihydrochloride, which has been shown to act as an inhibitor of cellular-mediated free-radical production. In the presence of histamine, cytotoxic effector function may be restored. The addition of histamine to IL-2-based cytokine therapies has resulted in enhanced in vitro cytotoxic T-cell and natural killer-cell function and has allowed for the development of lower, and thus, less toxic, IL-2 regimens. Preliminary studies of this combination in patients with acute myeloid leukemia in remission suggest improved survival with tolerable toxicity. The strategy for implementation of IL-2-based immunotherapy in patients with acute myeloid leukemia is reviewed.