Role of cytokines in the treatment of acute leukemias:: a review

Myeloid growth factors, such as granulocyte colony-stimulating factor and granulocyte-macrophage colony-stimulating factor, have been used to decrease the duration of chemotherapy-induced neutropenia and thereby reduce the incidence and severity of infections in various regimens used to treat acute myeloid leukemia and acute lymphoblastic leukemia. These growth factors have also been used to recruit dormant myeloid leukemia cells into the S phase of cell cycle in order to increase their susceptibility to the antileukemic effects of agents such as cytarabine. Multiple prospective randomized trials have examined the benefit and safety of the addition of growth factors before, during, and after chemotherapy. A reduction in the duration of neutropenia has been the most consistent finding; this has not been associated with stimulation of leukemia cells, the main concern of using this strategy. Unfortunately, few studies have reported a benefit in prolonging the duration of disease-free survival or overall survival. Other cytokines, including interleukins and thrombopoietin, have also been evaluated for their theoretical ability to recruit immune mechanisms to eradicate residual leukemia burden after chemotherapy, and to stimulate platelet production. In this review, we summarize the clinical experience with these growth factors in treating acute leukemias.