The Role of Colony-Stimulating Factors in the Treatment of Acute Leukaemia

Abstract

The currently available haemopoietic growth factors granulocyte colony-stimulating factor (G-CSF) and granulocyte-macrophage colony-stimulating factor (GM-CSF) have been used in the treatment of acute leukaemia with 2 objectives: to reduce the time to neutrophil recovery after intensive chemotherapy and/or haemopoietic progenitor transplantation; andin acute myeloid leukaemia, to recruit leukaemic cells into the cell cycle in order to increase the number of blasts susceptible to cycle-specific cytotoxic drugs. In acute lymphoblastic leukaemia, the use of G-CSF or GM-CSF shortens the duration of neutropenia, and may facilitate adherence to the chemotherapy schedule. However, only 1 study has demonstrated an increase in the complete remission rate, and this was in only 1 subgroup of patients (>60 years old). In acute myeloid leukaemia, the administration of G-CSF or GM-CSF after chemotherapy is well tolerated and is not associated with a stimulation of the leukaemic clone. In 4 out of 5 large randomised placebo-controlled studies, use of colony-stimulating factors led to a reduction of the duration of neutropenia. The complete remission rate was significantly higher for patients receiving growth factors in 2 studies, 1 with G-CSF and 1 with GM-CSF. However, only 1 of these studies, that with GM-CSF, demonstrated improved patient survival. The effect of G-CSF or GM-CSF given before and/or during chemotherapy of acute myeloid leukaemia has been evaluated in 4 randomised studies. The results are currently not sufficient to recommend the use of either growth factor in this indication. Many questions remain regarding the optimal dosage and schedule of administration of G-CSF or GM-CSF in acute leukaemia. The reduction of time to neutrophil recovery observed when the growth factor is administered after chemotherapy is not always translated into a benefit for the patient. Careful clinical and cost-effectiveness studies are necessary before routinely using these factors in clinical practice.