Treatment of drug-induced agranulocytosis with haematopoietic growth factors - A review of the clinical experience

Although drug-induced agranulocytosis is infrequent, it is of concern as th e mortality rate ranges from 6 to 10%. Since the approval of granulocyte co lony stimulating factor (G-CSF) and granulocyte-macrophage colony-stimulati ng factor (GM-CSF), these drugs have been increasingly used in the manageme nt of drug-induced agranulocytosis. Unfortunately, most of the data regardi ng the use of these agents in patients with drug-induced agranulocytosis co mes from case reports. In light of the low incidence of drug-induced agranu locytosis, 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 p erformed. Case reports provide promising results with a shortening in the duration of agranulocytosis, a possible reduction in the duration of hospitalisation a nd the fatality rate in patients treated with haematopoietic growth factors (HGF) compared with historical controls. A therapeutic effect is also sugg ested by reports of reductions in the neutrophil count after HGF discontinu ation 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 pa tients treated with HGF as compared with those receiving routine care. A Ja panese study indicated that G-CSF was effective in patients with mild-to-mo derate antithyroid drug-induced neutropenia, whereas no clear benefit was a pparent 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 decreas e in the overall mortality of drug-induced agranulocytosis. HGF are expecte d lo further reduce mortality. Guidelines for the use of HGF in patients wi th febrile neutropenia, as established by the American Society of Clinical Oncology, are probably valuable for the management of drug-induced agranulo cytosis. In accordance with these recommendations, the use of HGF may be re commended in patients with severe neutropenia and/or poor prognostic factor s. Whether the absence of myeloid precursors or presence of promyelocytes o r myelocytes in bone marrow examination represents optimal conditions for H GF treatment is still unknown. Most authors agree that treatment should be administered early in the course of the disease. An interesting approach, i n which treatment decisions are based on the granulocyte count 4 hours afte r a single dose of G-CSF in patients with anthithyroid drug-associated neut ropenia should be more extensively evaluated.