Growth factors in acute myeloid leukaemia

Abstract

Clinical trials of colony-stimulating factors (CSFs) have been conducted for over 10 years. Initially, these agents, generally either granulocyte-macrophage (GM)- or granulocyte (G)-CSF, were hypothesized to reduce rates of major infection and/or death in the initial weeks after administration of chemotherapy. Although trials have consistently shown that both cytokines accelerate neutrophil recovery, only 1 out of 5–10 large randomized trials has reported that a decrease in major infection occurs as a result. While some of these trials have found that the use of cytokines lowers days in hospital, on antibiotics, or with fever, it is unclear whether the magnitude of these effects outweighs the expense currently entailed in CSF administration; indeed it appears that estimates of cost are themselves quite variable. The second major use of cytokines has been in priming acute myeloid leukaemia (AML) blasts to the cytotoxic actions of chemotherapy. Here again, the results of several randomized trials do not justify application of this strategy. It remains possible that there are subsets of AML patients who would benefit from priming. However, the identification of such patients might require years of accrual into clinical trials from which the majority of patients would not benefit. Future years may see trials of cytokines (e.g. pegylated recombinant human megakaryocytic growth and development factor +G- or GM-CSF) in patients in remission and as a means to increase the number of normal granulocytes that can be given to patients with infections. Further therapies may target cytokine receptors on AML blasts, to improve anti-leukaemia therapy.