Pharmacodynamic Effects of Haematopoietic Cytokines: The View of a Clinical Oncologist

  The production of haematopoietic cells is under the tight control of a group of haematopoietic cytokines. Each cytokine has multiple actions mediated by receptors whose cytoplasmic domains contain specialized regions initiating survival, proliferation, differentiation commitment, maturation and functional activation. Granulocyte colony‐stimulating factor (G‐CSF), erythropoietin (EPO), and thrombopoiesis‐stimulating agents are in routine clinical use to stimulate cell production and in total have been used in the management of many millions of patients. G‐CSF regulates neutrophil production to maintain blood neutrophil counts in the normal range. G‐CSF is used to prevent febrile neutropenia or to increase dose‐density in chemotherapy regimens. Despite consistently showing a shorter duration of neutropenia, multiple prospective randomized trials have documented only modest clinical benefit. A clinical advantage of dose‐dense chemotherapy has been shown only in specific chemotherapy regimens. Professional recommendations tailor the use of CSFs to patients with a high risk of adverse outcome of febrile neutropenia. EPO was used to prevent anaemia requiring red blood cell transfusion. However, recent studies strongly suggest a negative overall effect on mortality, without a plausible biological explanation. It is now proposed that its use should be restricted to patients in clinical trials. Thrombopoiesis‐stimulating agents have only been recently introduced into the market for splenectomized and non‐splenectomized patients with immune thrombocytopenic purpura, a rare disease. Before widely used in other conditions such as chemotherapy‐induced thrombocytopenia, the lessons learned from the example of G‐CSF and EPO should be taken seriously.