Treatment of Drug-Induced Agranulocytosis with Haematopoietic Growth Factors

Abstract

Although drug-induced agranulocytosis is infrequent, it is of concern as the mortality rate ranges from 6 to 10%. Since the approval of granulocyte colony-stimulating factor (G-CSF) and granulocyte-macrophage colony-stimulating factor (GM-CSF), these drugs have been increasingly used in the management of drug-induced agranulocytosis. Unfortunately, most of the data regarding the use of these agents in patients with drug-induced agranulocytosis comes from case reports. In light of the low incidence of drug-induced agranulocytosis, the large variety of offending drugs with potentially different toxic mechanisms and the wide range of neutropenia duration among patients with agranulocytosis, randomised, double-blind studies are unlikely to be performed. Case reports provide promising results with a shortening in the duration of agranulocytosis, a possible reduction in the duration of hospitalisation and the fatality rate in patients treated with haematopoietic growth factors (HGF) compared with historical controls. A therapeutic effect is also suggested by reports of reductions in the neutrophil count after HGF discontinuation following an initial increase. The results of recent case series are less positive, with only a moderate, but usually not significant, reduction in the duration of neutropenia in patients treated with HGF, as compared with those receiving routine care. A Japanese study indicated that G-CSF was effective in patients with mild-to-moderate antithyroid drug-induced neutropenia, whereas no clear benefit was apparent in those with severe neutropenia. Several factors, for example, early recognition and improved management of individual cases with better supportive care, have contributed to a decrease in the overall mortality of drug-induced agranulocytosis. HGF are expected to further reduce mortality. Guidelines for the use of HGF in patients with febrile neutropenia, as established by the American Society of Clinical Oncology, are probably valuable for the management of drug-induced agranulocytosis. In accordance with these recommendations, the use of HGF may be recommended in patients with severe neutropenia and/or poor prognostic factors. Whether the absence of myeloid precursors or presence of promyelocytes or myelocytes in bone marrow examination represents optimal conditions for HGF treatment is still unknown. Most authors agree that treatment should be administered early in the course of the disease. An interesting approach, in which treatment decisions are based on the granulocyte count 4 hours after a single dose of G-CSF in patients with anthithyroid drug-associated neutropenia should be more extensively evaluated.