Blood 93/10

couple of hours later, there was swelling and reddening of the margins of the ulcers, frequently accompanied by fever up to 38°C. These symptoms lasted for a few hours and subsided spontaneously or with the help of minor analgesics. The patients tolerated this inconvenience, because they soon saw a favorable response. In fact, the latter was dramatic in three of them (patients no. 1, 2, and 4) in the sense that the rotten and unclean tissue was gradually replaced by healthy tissue and the ulcer healed completely in approximately 2 months (Fig 1). The ulcers of patient no. 3 showed remarkable improvement but not complete healing. This may be attributed to their large size, their severe persistent contamination with staphylococcus aureus and other Gram-negative bacteria (despite the intensive local care and systematic administration of the appropriate antibiotics), and the premature termination of therapy because of an acute inflammatory reaction extending from one of the ulcers up to her groin, which appeared by the end of the second week. To this date, several months after this treatment, the ulcers have not recurred. The assay of various cytokines showed a clear increase of IL-1 and TNF along with a decrease of IL-8 (Table 1). These changes probably account for the high temperature observed in the patients after the injections of GM-CSF. The fact that the number of leukocytes in the peripheral blood did not change after each injection suggests that the action of GM-CSF was mainly local. In conclusion, subcutaneous perilesional injections of GMCSF may play an important role in the healing of chronic ulcers in patients with hemoglobinopathies, especially when these have persisted over several years despite intensive treatment, as in the case of the patients of this report. Treatment is relatively well-tolerated and the associated side effects (pain and fever) respond easily to mild analgesics. The activity of GM-CSF is pleiotropic. It includes local attraction of neutrophils, hence improving the clearance of bacteria and debris, promotion of neovascularization, enhancement of keratinization, and acceleration of the formation of new tissue.